Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery Dale W

ASHP Report Antimicrobial prophylaxis

ASHP report

Clinical practice guidelines for antimicrobial prophylaxis in surgery Dale W. Bratzler, E. Patchen Dellinger, Keith M. Olsen, Trish M. Perl, Paul G. Auwaerter, Maureen K. Bolon, Douglas N. Fish, Lena M. Napolitano, Robert G. Sawyer, Douglas Slain, James P. Steinberg, and Robert A. Weinstein Am J Health-Syst Pharm. 2013; 70:195-283 hese guidelines were developed Prophylaxis refers to the preven- of the revised guidelines. The work jointly by the American Society tion of an infection and can be char- of the panel was facilitated by fac- Tof Health-System Pharmacists acterized as primary prophylaxis, ulty of the University of Pittsburgh (ASHP), the Infectious Diseases So- secondary prophylaxis, or eradica- School of Pharmacy and University ciety of America (IDSA), the Surgi- tion. Primary prophylaxis refers to of Pittsburgh Medical Center Drug cal Infection Society (SIS), and the the prevention of an initial infection. Use and Disease State Management Society for Healthcare Epidemiology Secondary prophylaxis refers to the Program who served as contract re- of America (SHEA). This work rep- prevention of recurrence or reactiva- searchers and writers for the project. resents an update to the previously tion of a preexisting infection. Eradi- Panel members and contractors were published ASHP Therapeutic Guide- cation refers to the elimination of a required to disclose any possible con- lines on Antimicrobial Prophylaxis in colonized organism to prevent the flicts of interest before their appoint- Surgery,1 as well as guidelines from development of an infection. These ment and throughout the guideline IDSA and SIS.2,3 The guidelines are guidelines focus on primary periop- development process. Drafted docu- intended to provide practitioners erative prophylaxis. ments for each surgical procedural with a standardized approach to the section were reviewed by the expert rational, safe, and effective use of Guidelines development and use panel and, once revised, were avail- antimicrobial agents for the preven- Members of ASHP, IDSA, SIS, and able for public comment on the tion of surgical-site infections (SSIs) SHEA were appointed to serve on an ASHP website. After additional revi- based on currently available clinical expert panel established to ensure sions were made to address reviewer evidence and emerging issues. the validity, reliability, and utility comments, the final document was

Dale W. Bratzler, D.O., M.P.H., is Professor and Associate Dean, Clinical Specialist, Critical Care/Infectious Diseases, Department of College of Public Health, and Professor, College of Medicine, Okla- Pharmacy Services, University of Colorado Hospital, Aurora. Lena homa University Health Sciences Center, Oklahoma City. E. Patchen M. Napolitano, M.D., FACS, FCCP, FCCM, is Professor of Surgery Dellinger, M.D., is Professor and Vice Chairman, Department and Division Chief, Acute Care Surgery, Trauma, Burn, Critical Care, of Surgery, and Chief, Division of General Surgery, University of Emergency Surgery, and Associate Chair of Surgery, Critical Care, Washington, Seattle. Keith M. Olsen, Pharm.D., FCCP, FCCM, is Department of Surgery, and Director, Surgical Critical Care, Uni- Professor of Pharmacy Practice, Nebraska Medical Center, Omaha. versity of Michigan Health System, Ann Arbor. Robert G. Sawyer, Trish M. Perl, M.D., M.Sc., is Professor of Medicine, Pathology, M.D., FACS, FIDSA, FCCM, is Professor of Surgery, Public Health and Epidemiology, Johns Hopkins University (JHU), and Senior Sciences, and Chief, Division of Acute Care, Surgery and Outcomes Epidemiologist, The Johns Hopkins Health System, Baltimore, Research, University of Virginia Health System, Charlottesville, MD. Paul G. Auwaerter, M.D., is Clinical Director and Associate VA. Douglas Slain, Pharm.D., BCPS, FCCP, FASHP, is Associate Professor, Division of Infectious Diseases, School of Medicine, JHU. Professor of Pharmacy and Medicine, West Virginia University, Mor- Maureen K. Bolon, M.D., M.S., is Associate Professor of Medi- gantown. James P. Steinberg, M.D., is Professor of Medicine, Divi- cine, Division of Infectious Diseases, Feinberg School of Medicine, sion of Infectious Diseases, Emory University, Atlanta, GA. Robert A. Northwestern University, Chicago, IL. Douglas N. Fish, Pharm.D., Weinstein, M.D., is C. Anderson Hedberg MD Professor of Internal FCCM, FCCP, BCPS, is Professor and Chair, Department of Clinical Medicine, Rush Medical College, Chicago, and Chairman, Department Pharmacy, University of Colorado, Anschultz Medical Campus, and of Medicine, Cook County Health and Hospital System, Chicago.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 195 ASHP Report Antimicrobial prophylaxis approved by the expert panel and legiate Guidelines Network, Medical evidence for a variety of therapeutic the boards of directors of the above- Letter, SIS, SHEA/IDSA) were also or diagnostic recommendations.4 named organizations. considered.2,3,5-11 Each recommendation was cat- Strength of evidence and grading Recommendations for the use of egorized according to the strength of recommendations. The primary antimicrobial prophylaxis are graded of evidence that supports the use or literature from the previous ASHP according to the strength of evidence nonuse of antimicrobial prophylaxis Therapeutic Guidelines on Antimi- available. The strength of evidence as category A (levels I–III), category crobial Prophylaxis in Surgery1 was represents only support for or against B (levels IV–VI), or category C (level reviewed together with the primary prophylaxis and does not apply to VII). literature published between the date the antimicrobial agent, dose, or When higher-level data are not of the previous guidelines, 1999, and dosage regimen. Studies supporting available, a category C recommen- June 2010, identified by searches the recommendations for the use of dation represents a consensus of of MEDLINE, EMBASE, and the antimicrobial therapy were classified expert panel members based on their Cochrane Database of Systematic as follows: clinical experience, extrapolation Reviews. Particular attention was from other procedures with similar paid to study design, with greatest • Level I (evidence from large, well- microbial or other clinical features, credence given to randomized, con- conducted, randomized, controlled and available published literature. trolled, double-blind studies. There clinical trials or a meta-analysis), In these cases, the expert panel also is a limited number of adequately • Level II (evidence from small, well- extrapolated general principles and powered randomized controlled conducted, randomized, controlled evidence from other procedures. trials evaluating the efficacy of an- clinical trials), Some recommendations include al- timicrobial prophylaxis in surgical • Level III (evidence from well- ternative approaches in situations in procedures. Guidelines develop- conducted cohort studies), which panel member opinions were ment included consideration of the • Level IV (evidence from well- divided. following characteristics: validity, conducted case–control studies), A major limitation of the available reliability, clinical applicability, flex- • Level V (evidence from uncontrolled literature on antimicrobial prophy- ibility, clarity, and a multidisciplinary studies that were not well conducted), laxis is the difficulty in establishing nature as consistent with ASHP’s • Level VI (conflicting evidence that significant differences in efficacy philosophy on therapeutic guide- tends to favor the recommendation), between prophylactic antimicrobial lines.4 The limitations of the evidence or agents and controls (including place- base are noted within each individual • Level VII (expert opinion or data ex- bo, no treatment, or other antimicro- procedure section of the guidelines. trapolated from evidence for general bial agents) due to study design and Published guidelines with recommen- principles and other procedures). low SSI rates for most procedures. A dations by experts in a procedure area small sample size increases the likeli- (e.g., American College of Obstetri- This system has been used by the hood of a Type II error; therefore, cians and Gynecologists [ACOG]) Agency for Healthcare Research and there may be no apparent difference and noted general guidelines (e.g., Quality, and ASHP, IDSA, SIS, and between the antimicrobial agent and Centers for Disease Control and SHEA support it as an acceptable placebo when in fact the antimicro- Prevention [CDC], Scottish Intercol- method for organizing strength of bial has a beneficial effect.12 A valid

The following individuals are acknowledged for their significant a grant from Merck; Dr. Auwaerter serves on the advisory panel of contributions to this manuscript: Sandra I. Berríos-Torres, M.D.; Genentech; Dr. Fish serves on the advisory board and speakers’ bu- Rachel Bongiorno-Karcher, Pharm.D.; Colleen M. Culley, Pharm.D., reau of Merck; and Dr. Sawyer serves as a consultant for Pfizer, Merck, BCPS; Susan R. Dombrowski, M.S., B.S.Pharm.; and Susan J. Skledar, Wyeth, 3M, and Ethicon and has received an R01 grant from the B.S.Pharm., M.P.H., FASHP. National Institute of General Medical Sciences and a T32 grant from Financial support provided by Emory University, Johns Hopkins the National Institute of Allergy and Infectious Diseases. Drs. Bolon, University, Northwestern University, Rush University, University of Napolitano, Olsen, Steinberg, Slain, and Weinstein have declared no Colorado, University of Michigan, University of Oklahoma, Univer- potential conflicts of interest. sity of Nebraska, University of Virginia, University of Washington, The bibliographic citation for this article is as follows: Bratzler and West Virginia University. DW, Dellinger EP, Olsen KM et al. Clinical practice guidelines for Dr. Bratzler is a consultant for Telligen; Dr. Dellinger has received antimicrobial prophylaxis in surgery. Am J Health-Syst Pharm. 2013; honoraria for participation on advisory boards and consultation for 70:195-283. Merck, Baxter, Ortho-McNeil, Targanta, Schering-Plough, WebEx, Astellas, Durata, Pfizer, Applied Medical, Rib-X, 3M, the American Copyright © 2013, American Society of Health-System Pharma- Hospital Association, Premier Inc., Oklahoma Foundation for Medi- cists, Inc. All rights reserved. 1079-2082/13/0201-0195$06.00. cal Quality, and the Hospital Association of New York State; Dr. Perl DOI 10.2146/ajhp120568 serves on the advisory boards of Hospira and Pfizer and has received

196 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis study is placebo controlled and randomized with a sufficient sample in each group to avoid a Type II error. Of note, prophylaxis is recommend- c ed in some cases due to the severity of complications of postoperative in-

fection (e.g., an infected device that 2 2 4 4 4 3 2 6 6 Continued on next page Continued NA NA NA NA NA NA is not easily removable) necessitating NA precautionary measures despite the lack of statistical support.

Summary of key updates. These Dose), hr Preoperative Recommended Redosing Recommended guidelines reflect substantial changes Initiation of Interval (From from the guidelines published in 1999.1 Highlights of those changes are outlined here. Preoperative-dose timing. The optimal time for administration of 19 preoperative doses is within 60 minutes before surgical incision. This 30 1–2 3–7 2–4 3–5 2–3 6–8 6–8 1–1.9 is a more-specific time frame than 0.8–1.3 1.3–2.4 1.2–2.2 0.9–1.7 0.7–1.1 2.8–4.6 5.4–10.9 the previously recommended time, Function, hr Function, Half-life in Adults in Adults Half-life which was “at induction of anesthe- Normal Renal With sia.” Some agents, such as fluoroquinolones and vancomycin, require administration over one to two hours; therefore, the administration of these agents should begin within 120 minutes before surgical incision. Selection and dosing. Information b is included regarding the approach 6 mg/kg component 50 mg/kg 30 mg/kg 30 mg/kg 50 mg/kg 50 mg/kg 40 mg/kg 40 mg/kg 10 mg/kg 10 mg/kg 15 mg/kg to weight-based dosing in obese pa- 10 mg/kg 15 mg/kg Pediatrics tients and the need for repeat doses 50–75 mg/kg during prolonged procedures.13-18 50 mg/kg of the ampicillin

Obesity has been linked to an in- a single 7.5-mg/kg dose receive 2.5 mg/kg based on dosing weight creased risk for SSI. The pharma- <1200 g should weighing Neonates cokinetics of drugs may be altered in obese patients, so dosage adjust- ments based on body weight may be warranted in these patients. For Dose Recommended

all patients, intraoperative redosing a e is needed to ensure adequate serum d 1 g 3 g 2 g 2 g 2 g 2 g 2 g 1 g and tissue concentrations of the 1.5 g 400 mg 900 mg 400 mg 500 mg 500 mg Adults antimicrobial if the duration of the (single dose) procedure exceeds two half-lives of the drug or there is excessive blood (ampicillin 2 g/sulbactam 1 g) 2 g, 3 g for pts weighing ≥ 120 kg pts weighing 3 g for 2 g, loss during the procedure (Table 5 mg/kg based on dosing weight 1). Recommendations for selection of antimicrobial agents for specific surgical procedures and alternative agents (e.g., for patients with aller- f f gies to b-lactam antimicrobials) are g provided in Table 2. Duration of prophylaxis. New rec- Antimicrobial Table 1. Table Prophylaxis Surgical for Antimicrobials Used Doses and Redosing IntervalsRecommended Commonly for ommendations for a shortened post- Ampicillin–sulbactam Ampicillin Aztreonam Cefazolin Cefuroxime Cefotaxime Cefoxitin Cefotetan Ceftriaxone Ciprofloxacin Clindamycin Ertapenem Fluconazole Gentamicin Levofloxacin Metronidazole

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 197 ASHP Report Antimicrobial prophylaxis

operative course of antimicrobials involving a single dose or continuation for less than 24 hours are pro- c vided. Further clarity on the lack of need for postoperative antimicrobial prophylaxis based on the presence of indwelling drains and intravascular 2 NA NA NA NA NA catheters is included. Common principles. A section addressing concepts that apply to all

Preoperative Dose), hr Preoperative types of surgical procedures has been Recommended Redosing Recommended Interval (From Initiation of Interval (From added. Expanded and new recommendations are provided for plastic, urology, cardiac, and thoracic procedures, as well as clarity on prophylaxis when implantable devices are inserted. The latest information on 19 the use of mupirocin and on the role of vancomycin in surgical prophy- 4–8 8–15 6–10 0.8–3

0.7–1.2 laxis is summarized in these updated guidelines. Function, hr Function, Half-life in Adults in Adults Half-life

With Normal Renal With Application of guidelines to clini- gastrointestinal conditions) gastrointestinal cal practice. Recommendations are

2–3 (3% absorbed under normal provided for adult (age 19 years or older) and pediatric (age 1–18 years) patients. These guidelines do not specifically address newborn (premature and full-term) infants. b While the guidelines do not address all concerns for patients with renal component

10 mg/kg 15 mg/kg 20 mg/kg 15 mg/kg 15 mg/kg or hepatic dysfunction, antimicrobial Pediatrics prophylaxis often does not need to

piperacillin component component piperacillin be modified for these patients when 100 mg/kg of the piperacillin 100 mg/kg of the piperacillin Children >9 mo and ≤ 40 kg: Children given as a single preoperative dose Infants 2–9 mo: 80 mg/kg of the before surgical incision. The recommendations herein may not be appropriate for use in all clinical situations. Decisions to experts recommend 2 g for obese patients. experts 2 g for recommend 14 Recommended Dose Recommended follow these recommendations must

a be based on the judgment of the clini- cian and consideration of individual 1 g 1 g 1 g

3.375 g patient circumstances and available 400 mg Adults 15 mg/kg resources. These guidelines reflect current knowledge of antimicrobial prophylaxis in surgery. Given the dynamic nature of scientific information and technology, periodic review, updat- ing, and revisions are to be expected. Special patient populations. Pe- f diatric patients. Pediatric patients undergo a number of procedures Antimicrobial similar to adults that may warrant The maximum pediatric dose should not exceed the usual adult dose. maximum pediatric dose should not exceed The Although FDA-approved package insert 1 g, Although FDA-approved labeling indicates In general, gentamicin for surgical antibiotic prophylaxis should be limited to a single dose given preoperatively. Dosing is based on the patient’s actual body weight. If the patient’s actual weight is more than 20% above than 20% above is more actual weight If actual the patient’s body weight. Dosing is based on the patient’s preoperatively. a single dose given to should be limited prophylaxis antibiotic surgical for gentamicin In general, When used as a single dose in combination with metronidazole for colorectal procedures. colorectal for with metronidazole used as a single dose in combination When Adult doses are obtained from the studies cited in each section. When doses differed between studies, expert studies, between opinion used the most-often dose. recommended doses differed When in each section. the studies cited obtained from doses are Adult For antimicrobials with a short half-life (e.g., cefazolin, cefoxitin) used before long procedures, redosing in the operating room is recommended at an interval of approximately two times the half-life of the agent in patients in patients of the agent times the half-life two an interval at of approximately is recommended room in the operating redosing long procedures, used before cefoxitin) cefazolin, with a short (e.g., antimicrobials half-life For While fluoroquinolones have been associated with an increased risk of tendinitis/tendon rupture in all ages, use of these agents for single-dose use of these agents safe. is generally in all ages, rupture tendinitis/tendon prophylaxis risk of with an increased been associated have fluoroquinolones While a b c d e f g ) 1 ( continued Table Moxifloxacin Piperacillin–tazobactam Vancomycin preparation) bowel with a mechanical surgery(used in conjunction antibiotics for colorectal prophylaxis Oral base Erythromycin Metronidazole Neomycin antimicrobial prophylaxis. Although ideal body weight (IBW),ideal body weight (DW) the dosing weight DW = IBW – IBW). + 0.4(actual weight as follows: can be determined with normal renal function. Recommended redosing intervals marked as “not applicable” (NA) are based on typical case length; for unusually long procedures, redosing may be needed. may redosing unusually long procedures, based on typical case length; for are (NA) applicable” “not function. intervalswith normal renal redosing marked Recommended as

198 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis c C C C A A A A A A A A A Evidence Strength of Strength Continued on next page Continued or or or g g g h-j h-j or or g g d d d or aztreonam or or aztreonam or or aztreonam or or aztreonam or or aztreonam h-j h-j h-j h-j h-j h-j h-j g g g g vancomycin vancomycin vancomycin vancomycin vancomycin d d d -Lactam Allergy b Alternative Agents in Pts With With in Pts Agents Alternative aztreonam or fluoroquinolone aztreonam or fluoroquinolone aztreonam fluoroquinolone fluoroquinolone fluoroquinolone aminoglycoside aminoglycoside aminoglycoside aminoglycoside fluoroquinolone fluoroquinolone fluoroquinolone fluoroquinolone Clindamycin or vancomycin + or vancomycin Clindamycin + or vancomycin Clindamycin + aminoglycoside Metronidazole None + or vancomycin Clindamycin + aminoglycoside Metronidazole + aminoglycoside Clindamycin + aminoglycoside Metronidazole + aminoglycoside Clindamycin Clindamycin, Clindamycin, + or vancomycin Clindamycin Clindamycin, Clindamycin, Clindamycin,

k k a,b h h Recommended Agents Recommended ampicillin–sulbactam ampicillin–sulbactam None ceftriaxone, cefotetan, cefoxitin, Cefazolin, + metronidazole cefazolin cefotetan, Cefoxitin, Cefazolin Cefazolin, cefuroxime Cefazolin, cefuroxime Cefazolin, cefuroxime Cefazolin, ampicillin–sulbactam Cefazolin, ampicillin–sulbactam Cefazolin, Cefazolin Cefazolin ceftriaxone, cefotetan, cefoxitin, Cefazolin, ) f l Type of Procedure Type l e pneumonectomy, lung resection, and thoracotomy pneumonectomy, tract pancreaticoduodenectomy (bariatric, (antireflux, highly selective vagotomy) for high-risk vagotomy) highly selective (antireflux, Coronary artery bypass pacemaker (e.g., insertion device Cardiac procedures assist devices Ventricular including lobectomy, procedures, Noncardiac surgery thoracoscopic Video-assisted entry lumen of gastrointestinal into involving Procedures high-risk Elective, Procedures without entry into gastrointestinal tract without entry gastrointestinal into Procedures Open procedure procedure Laparoscopic low-risk Elective, Table 2. Table Prophylaxis Antimicrobial Surgical for Recommendations Cardiac appendicitis uncomplicated for Appendectomy Small intestine Nonobstructed implantation) Thoracic Gastroduodenal

patients patients Biliary tract

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 199 ASHP Report Antimicrobial prophylaxis c B B B C C C C A A A A A A A Evidence Strength of Strength Continued on next page Continued or g , or or g g h-j or g g

d d d or aztreonam or or aztreonam h-j h-j h-j h-j g vancomycin vancomycin vancomycin d d d d d d -Lactam Allergy b Alternative Agents in Pts With With in Pts Agents Alternative aztreonam or fluoroquinolone aztreonam fluoroquinolone fluoroquinolone aminoglycoside fluoroquinolone fluoroquinolone metronidazole + aminoglycoside metronidazole Clindamycin, vancomycin Clindamycin, + aminoglycoside Clindamycin None Clindamycin Clindamycin Clindamycin Clindamycin, Clindamycin, + aminoglycoside Clindamycin + or vancomycin Clindamycin Metronidazole + aminoglycoside Metronidazole None None Clindamycin, Metronidazole + aminoglycoside Metronidazole a,b o ceftriaxone + ceftriaxone h ertapenem n h Recommended Agents Recommended ampicillin–sulbactam, fourth-generation fluoroquinolones topical drop as 1 given or moxifloxacin) (gatifloxacin every 5 doses 5–15 min for 1–2.5 mg cefazolin injection or intracameral is the end of procedure 1 mg at or cefuroxime optional metronidazole, ampicillin–sulbactam metronidazole, ampicillin–sulbactam metronidazole, sulbactam metronidazole, Cefazolin + metronidazole, cefoxitin, cefotetan cefoxitin, + metronidazole, Cefazolin Cefazolin cefotetan, cefoxitin, + metronidazole, Cefazolin Topical neomycin–polymyxin B–gramicidin or neomycin–polymyxin Topical subconjunctival 100 mg by of cefazolin Addition None Cefazolin None cefuroxime Cefazolin, + cefuroxime + metronidazole, Cefazolin + cefuroxime + metronidazole, Cefazolin Cefazolin Cefazolin Cefazolin ampicillin– cefoxitin, cefotetan, Cefazolin, Type of Procedure Type m tonsillectomy and functional sinus procedures tonsillectomy endoscopic involving implantation of foreign materials of foreign implantation involving Clean with placement of prosthesis (excludes tympanostomy (excludes of prosthesis Clean with placement surgery cancer Clean-contaminated of with the exception Other procedures clean-contaminated fluid-shunting and cerebrospinal Elective craniotomy pumps Implantation of intrathecal and not knee, or foot hand, involving Clean operations with and without instrumentation Spinal procedures continued) 2 ( continued) Table

tubes) procedures delivery Cesarean or abdominal) (vaginal Hysterectomy Ophthalmic Orthopedic Obstructed (hernioplastyHernia repair and herniorrhaphy) Colorectal Head and neck Clean Neurosurgery

200 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis c B C A A A A A A A A A A cardiac cardiac cardiac procedures) procedures) Evidence A (based on A (based on Strength of Strength Continued on next page Continued + g g d d d d d d d or aztreonam or or aztreonam or aztreonam or or aztreonam or or aztreonam aminoglycoside aminoglycoside h-j h-j h-j g g g h-j h-j with or without g vancomycin vancomycin vancomycin vancomycin vancomycin vancomycin vancomycin d d d d d d d -Lactam Allergy b Alternative Agents in Pts With With in Pts Agents Alternative clindamycin or aztreonam, vancomycin ± vancomycin or aztreonam, or aztreonam aminoglycoside aminoglycoside aminoglycoside aminoglycoside fluoroquinolone fluoroquinolone fluoroquinolone with or without clindamycin or clindamycin metronidazole Clindamycin, Clindamycin, Clindamycin, Aminoglycoside ± aminoglycoside Clindamycin Fluoroquinolone, Clindamycin, Clindamycin, + or vancomycin Clindamycin + or vancomycin Clindamycin + or vancomycin Clindamycin Fluoroquinolone, Clindamycin, Clindamycin, a,b trimethoprim– h-j Recommended Agents Recommended sulfamethoxazole, cefazolin sulfamethoxazole, for be recommended may aminoglycoside penile [e.g., material of prosthetic placement prosthesis]) ampicillin–sulbactam for be recommended may aminoglycoside penile [e.g., material of prosthetic placement prosthesis]) those with enteric of fungal infection [e.g., of the pancreas]) drainage Cefazolin Cefazolin Cefazolin Fluoroquinolone, Cefazolin (the addition of a single dose an Cefazolin ± aztreonam, cefazolin ± aminoglycoside, Cefazolin (the addition of a single dose an Cefazolin cefoxitin + metronidazole, Cefazolin Cefazolin Cefazolin Cefazolin + ampicillin cefotaxime Piperacillin–tazobactam, at high risk patients (for fluconazole Cefazolin, Cefazolin

r (e.g., nails, screws, screws, nails, (e.g.,

r,s q r Type of Procedure Type q,t

p (includes transrectal prostate biopsy) prostate (includes transrectal Involving implanted prosthesis implanted Involving Hip repair fracture devices fixation Implantation of internal Heart transplantation and heart–lungLung transplantation Clean without entry urinary into tract Clean with entry urinary into tract Total joint replacement joint Total infection tractwith risk factors instrumentation for Lower continued) 2 ( continued) Table

transplantation Liver and pancreas–kidney transplantation Pancreas Heart, heart–lung lung, transplantation

Clean-contaminated Vascular plates, wires) plates, Urologic

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 201 ASHP Report Antimicrobial prophylaxis

c C -lactam allergic; b -lactamallergic; Evidence Strength of Strength -receptor antagonists or proton-pump or proton-pump antagonists -receptor 2

d vancomycin d -Lactam Allergy b Alternative Agents in Pts With With in Pts Agents Alternative Clindamycin, a,b Recommended Agents Recommended Cefazolin, ampicillin–sulbactam Cefazolin,

Type of Procedure Type Clean with risk factors or clean-contaminated For most patients, a mechanical bowel preparation combined with oral neomycin sulfate plus oral erythromycin base or with oral neomycin sulfate plus oral metronidazole should be given in addition to i.v. prophylaxis. i.v. in addition to should be given metronidazole plus oral sulfate neomycin base or with oral erythromycin plus oral sulfate neomycin with oral combined preparation a mechanical bowel most patients, For Strength of evidence that supports the use or nonuse of prophylaxis is classified as A (levels I–III), B (levels IV–VI), or C (level VII). Level I evidence is from large, well-conducted, randomized controlled clinical trials. Level II Level clinical trials. controlled well-conducted,randomized large, is from I evidence Level VII). or C (level IV–VI), I–III), B (levels supports is classified as A (levels that of evidence Strength the use or nonuse of prophylaxis Factors that indicate a high risk of infectious complications in laparoscopic cholecystectomy include emergency procedures, diabetes, long procedure duration, intraoperative gallbladder rupture, age of >70 years, age of >70 years, gallbladder rupture, intraoperative duration, long procedure diabetes, cholecystectomy include emergency procedures, in laparoscopic risk a high of infectious complications indicate that Factors , it is reasonable to add a single preoperative dose of vancomycin to the recommended agent(s). the recommended to dose of vancomycin add a single preoperative to , it is reasonable aureus Staphylococcus with methicillin-resistant known be colonized patients to For carotid (e.g., implantation or patch prostheses vascular involving procedures in support, no data brachiocephalic are undergoing Although there patients procedures. brachiocephalic for indicated is not routinely Prophylaxis For procedures in which pathogens other than staphylococci and streptococci are likely, an additional agent with activity against those pathogens could be considered. For example, if there are surveillance data showing surveillance showing data are if there example, For with activity an additional agent be considered. could against those pathogens likely, are and streptococci other than staphylococci in which pathogens procedures For These guidelines reflect recommendations for perioperative antibiotic prophylaxis to prevent SSIs and do not provide recommendations for prevention of opportunistic transplantation for prevention infections in immunosuppressed recommendations SSIs and do not provide to prevent prophylaxis antibiotic for perioperative recommendations guidelines reflect These Gentamicin or tobramycin. to fluoroquinolones and ampicillin–sulbactam, local population susceptibility profiles should be reviewed prior to use. prior reviewed and ampicillin–sulbactam, should be susceptibility fluoroquinolones profiles local population to of Escherichia coli resistance increasing Due to routine use of carbapenems. the over be preferred may ceftriaxone plus metronidazole a single dose of SSIs, from isolates gram-negative cephalosporins among and second-generation first- to resistance is increasing there Where The necessity of continuing topical antimicrobials postoperatively has not been established. postoperatively antimicrobials topical necessity of continuing The Consider additional antimicrobial coverage with infected biliary with infected tract. See coverage the biliary section additional antimicrobial Consider of this article. tract procedures Prophylaxis should be considered for patients at highest risk for postoperative gastroduodenal infections, such as those with increased gastric pH (e.g., those receiving histamine H those receiving gastric pH (e.g., such as those with increased infections, gastroduodenal postoperative highest risk at for patients for should be considered Prophylaxis The antimicrobial agent should be started within 60 minutes before surgical incision (120 minutes for vancomycin or fluoroquinolones). While single-dose prophylaxis is usually sufficient, the duration of prophylaxis for While single-doseprophylaxis of duration the is usually sufficient, prophylaxis or fluoroquinolones). vancomycin for incision (120 minutes surgical should be started agent before antimicrobial within 60 minutes The Ceftriaxone use should be limited to patients requiring antimicrobial treatment for acute cholecystitis acute biliary cholecystectomy or acute for undergoing incision, not patients prior tractnot be determined to treatment infections which may antimicrobial requiring patients to use should be limited Ceftriaxone ) or fungal organisms, isolated from the donor lung or from isolated ) or fungal organisms, aeruginosa Pseudomonas (e.g., gram-negative including pathogens, potential against any coverage to provide be modified need to may regimen prophylactic The The prophylactic regimen may need to be modified to provide coverage against any potential pathogens, including vancomycin-resistant enterococci, isolated from the recipient before transplantation. transplantation. before recipient the from isolated enterococci, vancomycin-resistant including pathogens, potential against any coverage to provide be modified need to may regimen prophylactic The Patients who have left-ventricular assist devices as a bridge and who are chronically infected might also benefit from coverage of the infecting microorganism. coverage also benefit from might infected chronically as a bridge and who are assist devices left-ventricular who have Patients Fluoroquinolones are associated with an increased risk of tendonitis and tendon rupture in all ages. However, this risk would be expected to be quite small with single-dose be expected be quite Although the use of this risk to would prophylaxis. antibiotic However, in all ages. rupture and tendon risk of tendonitis with an increased associated are Fluoroquinolones Ciprofloxacin or levofloxacin. Ciprofloxacin q a b c d e f g h i j k l m n p r s t o continued) 2 ( continued) Table Plastic surgeryPlastic recipient before transplantation. Patients undergoing lung transplantation with negative pretransplantation cultures should receive antimicrobial prophylaxis as appropriate for other types of cardiothoracic surgeries. Patients Patients surgeries. other types of cardiothoracic for as appropriate prophylaxis antimicrobial should receive cultures pretransplantation with negative lung transplantation undergoing Patients transplantation. before recipient include additional may This treatment results. and susceptibility culture to pretransplantation selected according with antimicrobials of treatment 7–14 days receive cystic should fibrosis for lung transplantation undergoing antibacterial agents. or antifungal evidence is from small, well-conducted, randomized controlled clinical trials. Level III evidence is from well-conducted cohort studies. Level IV evidence is from well-conducted case–control studies. Level V evidence is from is from V evidence well-conducted case–control is from IV evidence well-conductedLevel cohort is from studies. III evidence Level studies. Level clinical trials. controlled randomized well-conducted, small, is from evidence is expert VII evidence opinion. Level recommendation. the to favor tends is conflicting that VI evidence evidence Level conducted. not well were studies that uncontrolled all procedures should be less than 24 hours. If an agent with a short half-life is used (e.g., cefazolin, cefoxitin), it should be readministered if the procedure duration exceeds the recommended redosing interval (from the time the interval (from redosing recommended the exceeds duration procedure the if readministered be should it cefoxitin), cefazolin, If shorta with agent (e.g., an used is hours. 24 than less be should half-life procedures all (e.g., agent shorten other factorsof the prophylactic may that are the half-life or if there bleeding occurs or excessive if prolonged also be warranted may 1]). Readministration Table dose [see of the preoperative of initiation insufficiency with renal patients or failure). (e.g., be prolonged may of the agent in whom the half-life in patients not be warranted may burns).extensive Readministration inhibitors), gastroduodenal perforation, decreased gastric motility, gastric outlet obstruction, gastric bleeding, morbid obesity, or cancer. Antimicrobial prophylaxis may not be needed when the lumen of the intestinal tract is not be needed when the lumen of intestinal may prophylaxis Antimicrobial or cancer. gastric outlet obstruction, morbid obesity, gastric bleeding, gastric perforation, motility, decreased gastroduodenal inhibitors), not entered. patients (e.g., for antifungal or antiviral medications). or antiviral antifungal for (e.g., patients conversion from laparoscopic to open cholecystectomy, American Society of Anesthesiologists classification of 3 or greater, episode of colic within 30 days before the procedure, reintervention in less than one month for reintervention in less than one month the procedure, before colic within 30 days episode of Americangreater, Society of 3 or classification of Anesthesiologists open cholecystectomy, to laparoscopic from conversion Because and insertiona number of these risk not possible to factors immunosuppression, are device. of prosthetic nonfunctioning gallbladder, pregnancy, jaundice, cholecystitis, bile spillage, acute noninfectious complication, cholecystectomy. laparoscopic undergoing all patients to prophylaxis a single dose of antimicrobial give to be reasonable intervention, it may surgical before determine aztreonam, gentamicin, or single-dose gentamicin, aztreonam, is b -lactam if the patient allergic). fluoroquinolone that gram-negative organisms are a cause of surgical-site infections (SSIs) for the procedure, practitioners may consider combining clindamycin or vancomycin with another agent (cefazolin if the patient is not is patient the if (cefazolin agent another with vancomycin or clindamycin combining consider practitioners may procedure, the for (SSIs) infections surgical-site of cause a are organisms gram-negative that for noninfected biliary noninfected including biliaryfor conditions, or dyskinesia colic without infection. endarterectomy) may benefit from prophylaxis. benefit from endarterectomy) may fluoroquinolones may be necessary for surgical antibiotic prophylaxis in some children, they are not drugs of first choice in the pediatric population due to an increased incidence of adverse events as compared with controls controls with compared as events of adverse incidence to an increased due in the pediatric population not drugs of first choice they are in some children, prophylaxis antibiotic be necessaryfor surgical may fluoroquinolones in some clinical trials.

202 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis pediatric-specific prophylaxis data patients because of the potential for Common principles and procedure- are sparse, available data have been toxicity in this population. The same specific guidelines. The Common evaluated and are presented in some principle of preoperative dosing Principles section has been devel- of the procedure-specific sections within 60 minutes before incision has oped to provide information com- of these guidelines. Selection of been applied to pediatric patients.20-23 mon to many surgical procedures. antimicrobial prophylactic agents Additional intraoperative dosing These principles are general recom- mirrors that in adult guidelines, with may be needed if the duration of mendations based on currently avail- the agents of choice being first- and the procedure exceeds two half-lives able data at the time of publication second-generation cephalosporins, of the antimicrobial agent or there that may change over time; therefore, reserving the use of vancomycin for is excessive blood loss during the these principles need to be applied patients with documented b-lactam procedure.19,21 As with adult patients, with careful attention to each clinical allergies.19,20 While the use of a pen- single-dose prophylaxis is usually situation. Detailed information per- icillin with a b-lactamase inhibitor sufficient. If antimicrobial prophy- tinent to specific surgical procedures in combination with cefazolin or laxis is continued postoperatively, is included in the procedure-specific vancomycin and gentamicin has also the duration should be less than 24 sections of these guidelines. been studied in pediatric patients, hours, regardless of the presence of In addition to patient- and the number of patients included in intravascular catheters or indwelling procedure-specific considerations, these evaluations remains small.20-23 drains.19,22,23,31,32 There are sufficient several institution-specific factors As with adults, there is little evidence pharmacokinetic studies of most must be considered by practitioners supporting the use of vancomycin, agents to recommend pediatric dos- before instituting these guidelines. alone or in combination with other ages that provide adequate systemic The availability of antimicrobial antimicrobials, for routine perioper- exposure and, presumably, efficacy agents at the institution may be re- ative antimicrobial prophylaxis in in- comparable to that demonstrated in stricted by local antimicrobial-use stitutions that have a high prevalence adults. Therefore, the pediatric dos- policy or lack of approval for use by of methicillin-resistant Staphylococ- ages provided in these guidelines are regulatory authorities. Medications cus aureus (MRSA). Vancomycin may based largely on pharmacokinetic that are no longer available or not ap- be considered in children known data and the extrapolation of adult proved for use by the Food and Drug to be colonized with MRSA and, in efficacy data to pediatric patients. Administration (FDA) are so noted. one retrospective historical cohort Because few clinical trials have been Local resistance patterns should also study, was shown to decrease MRSA conducted in pediatric surgical pa- be considered in selecting antimicro- infections.21 Mupirocin use has been tients, strength of evidence criteria bial agents and are discussed in the studied in and is efficacious in chil- have not been applied to these rec- colonization and resistance patterns dren colonized with MRSA, but there ommendations. With few exceptions section of the Common Principles are limited data supporting its use (e.g., aminoglycoside dosages), pe- section. perioperatively.24-30 However, there is diatric dosages should not exceed the little reason to think that the impact maximum adult recommended dos- Requirements for effective and effect would be any different in ages. Generally, if dosages are calculat- surgical prophylaxis children, so its use may be justified. ed on a milligram-per-kilogram basis Appendix A lists the wound clas- Additional studies in this setting are for children weighing more than 40 sification criteria currently used by needed to establish firm guidelines. kg, the calculated dosage will exceed the CDC National Healthcare Safety Unless noted in specific sections, the maximum recommended dosage Network (NHSN) and Healthcare all recommendations for adults for adults; adult dosages should there- Infection Control Practices Advisory are the same for pediatric patients, fore be used. Committee (HICPAC).33-35 except for dosing. In most cases, Patients with prosthetic implants. Criteria for defining an SSI have the data in pediatric patients are For patients with existing prosthetic also been established by NHSN (Ap- limited and have been extrapolated implants who undergo an invasive pendix B).8,36 These definitions as- from adult data; therefore, nearly procedure, there is no evidence that sist in evaluating the importance of all pediatric recommendations are antimicrobial prophylaxis prevents providing antimicrobial prophylaxis based on expert opinion. In some infections of the implant. However, and the potential consequences of sections, pediatric efficacy data do updated guidelines from the Ameri- infection, including the need for not exist and thus are not addressed can Heart Association (AHA) suggest treatment. Some criteria vary slightly in these guidelines. Fluoroquino- that prophylaxis may be justified in by procedure. lones should not be routinely used a limited subset of patients for the Although antimicrobial prophy- for surgical prophylaxis in pediatric prevention of endocarditis.11 laxis plays an important role in reduc-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 203 ASHP Report Antimicrobial prophylaxis ing the rate of SSIs, other factors such treating and the morbidity associ- The SIP project was expanded to as attention to basic infection-control ated with infection compared with SCIP to include additional process strategies,37 the surgeon’s experience the cost and morbidity associated measures surrounding patient safety and technique, the duration of the with using prophylaxis. Antimicrobial and care during surgical procedures, procedure, hospital and operating- prophylaxis is justified for most clean- including glucose control, venous room environments, instrument- contaminated procedures. The use of thromboembolism prophylaxis, hair sterilization issues, preoperative prep- antimicrobial agents for dirty pro- removal, and temperature control. aration (e.g., surgical scrub, skin cedures (Appendix A) or established Similar measures have been adopted antisepsis, appropriate hair removal), infections is classified as treatment of by the Joint Commission.43 The Phy- perioperative management (tempera- presumed infection, not prophylaxis. sicians Quality Reporting System was ture and glycemic control), and the See the procedure-specific sections for established in 2006 to provide finan- underlying medical condition of the detailed recommendations. cial incentives to physicians meeting patient may have a strong impact on Quality-improvement efforts. performance standards for quality SSI rates.5,8 These guidelines recognize National, state, local, and institu- measures, including surgery-related the importance of these other factors tional groups have developed and measures similar to those reported but do not include a discussion of implemented collaborative efforts to for SCIP and the Joint Commis- or any recommendations regarding improve the appropriateness of sur- sion.44 Data are required to be col- these issues beyond the optimal use gical antimicrobial prophylaxis. Vari- lected by institutions and reported of prophylactic antimicrobial agents. ous process and outcomes measures to payers.42,44,46 Data for CMS and the Patient-related factors associated are employed, and results are dis- Physicians Quality Reporting System with an increased risk of SSI include seminated. Institutional epidemiol- measures are displayed on public extremes of age, nutritional status, ogy and infection-control programs, websites to allow consumers to com- obesity, diabetes mellitus, tobacco use, state-based quality-improvement pare performance among hospitals. coexistent remote body-site infec- campaigns (e.g., the Michigan Sur- Institutional data collection and tions, altered immune response, cor- gical Quality Collaborative, the reporting are required, with financial ticosteroid therapy, recent surgical Washington State Surgical Clinical incentives tied to performance to procedure, length of preoperative Outcomes Assessment Program39,40), varying degrees, including payment hospitalization, and colonization CDC, NHSN, the National Surgical for reporting, payment increases with microorganisms. Antimicro- Quality Improvement Program, the for meeting or exceeding minimum bial prophylaxis may be justified for Joint Commission, and the National levels of performance, payment re- any procedure if the patient has an Quality Forum have been instru- duction for poor performance, and underlying medical condition as- mental in developing programs to lack of payment for the development sociated with a high risk of SSI or if prevent SSIs. of surgical complications, such as the patient is immunocompromised Over the past decade or more, mediastinitis. (e.g., malnourished, neutrope- several organizations, payers, and Quality-improvement initiatives nic, receiving immunosuppressive government agencies, including the and mandated performance report- agents). Centers for Medicare and Medicaid ing are subject to change, so readers Antimicrobial prophylaxis may Services (CMS), have established of these guidelines are advised to be beneficial in surgical procedures national quality-improvement initia- consult their local or institutional associated with a high rate of infec- tives to further improve the safety quality-improvement departments tion (i.e., clean-contaminated or and outcomes of health care, includ- for new developments in require- contaminated procedures) and in ing surgery.41-47 One area of focus ments for measures and data report- certain clean procedures where there in these initiatives for patients un- ing that apply to their practice. are severe consequences of infection dergoing surgical procedures is the Cost containment. Few pharma- (e.g., prosthetic implants), even if in- prevention of SSIs. The performance coeconomic studies have addresed fection is unlikely. While prophylac- measures used, data collection and surgical antimicrobial prophylaxis; tic antimicrobials are not indicated reporting requirements, and finan- therefore, a cost-minimization ap- for some clean surgical procedures,8 cial implications vary among the ini- proach was employed in developing available data suggest that the rela- tiatives. The Surgical Care Improve- these guidelines. The antimicrobial tive risk reduction of SSI from the ment Project (SCIP) began in 2002 agent recommendations are based use of antimicrobial prophylaxis is as the Surgical Infection Prevention primarily on efficacy and safety. In- the same in clean and in higher-risk (SIP) project, focusing on the tim- dividual institutions must consider procedures.38 The decision to use ing, selection, and duration of pro- their acquisition costs when imple- prophylaxis depends on the cost of phylactic antimicrobial agents.41,42 menting these guidelines.

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Additional cost savings may be use. For most procedures, cefazolin over the past two decades. Analysis of realized through collaborative man- is the drug of choice for prophylaxis National Nosocomial Infections Sur- agement by pharmacists and sur- because it is the most widely studied veillance (NNIS) System data found geons to select the most cost-effective antimicrobial agent, with proven ef- that the percentage of SSIs caused by agent and minimize or eliminate ficacy. It has a desirable duration of gram-negative bacilli decreased from postoperative dosing.48-50 The use action, spectrum of activity against 56.5% in 1986 to 33.8% in 2003.68 of standardized antimicrobial order organisms commonly encountered S. aureus was the most common sets, automatic stop-order programs, in surgery, reasonable safety, and low pathogen, causing 22.5% of SSIs and educational initiatives has been cost. There is little evidence to suggest during this time period. NHSN data shown to facilitate the adoption of that broad-spectrum antimicrobial from 2006 to 2007 revealed that the guidelines for surgical antimicrobial agents (i.e., agents with broad in vitro proportion of SSIs caused by S. au- prophylaxis.51-58 antibacterial activity) result in lower reus increased to 30%, with MRSA rates of postoperative SSI compared comprising 49.2% of these isolates.61 Common principles with older antimicrobial agents with In a study of patients readmitted Ideally, an antimicrobial agent a narrower spectrum of activity. How- to U.S. hospitals between 2003 and for surgical prophylaxis should (1) ever, comparative studies are limited 2007 with a culture-confirmed SSI, prevent SSI, (2) prevent SSI-related by small sample sizes, resulting in dif- the proportion of infections caused morbidity and mortality, (3) reduce ficulty detecting a significant differ- by MRSA increased significantly the duration and cost of health care ence between antimicrobial agents; from 16.1% to 20.6% (p < 0.0001).69 (when the costs associated with the therefore, antimicrobial selection is MRSA infections were associated management of SSI are considered, based on cost, safety profile, ease of ad- with higher mortality rates, longer the cost-effectiveness of prophylaxis ministration, pharmacokinetic profile, hospital stays, and higher hospital becomes evident),51,52 (4) produce and bactericidal activity. costs compared with other infections. no adverse effects, and (5) have no Spectrum of activity. Antimi- adverse consequences for the mi- Common surgical pathogens crobial agents with the narrowest crobial flora of the patient or the The agent chosen should have spectrum of activity required for hospital.53 To achieve these goals, an activity against the most common efficacy in preventing infection are antimicrobial agent should be (1) ac- surgical-site pathogens. The pre- recommended in these guidelines. tive against the pathogens most likely dominant organisms causing SSIs after Alternative antimicrobial agents to contaminate the surgical site, (2) clean procedures are skin flora, includ- with documented efficacy are also given in an appropriate dosage and at ing S. aureus and coagulase-negative listed herein. Individual health sys- a time that ensures adequate serum staphylococci (e.g., Staphylococcus tems must consider local resistance and tissue concentrations during the epidermidis).61 In clean-contaminated patterns of organisms and overall period of potential contamination, procedures, including abdominal pro- SSI rates at their site when adopting (3) safe, and (4) administered for the cedures and heart, kidney, and liver these recommendations. Resistance shortest effective period to minimize transplantations, the predominant patterns from organisms causing adverse effects, the development of organisms include gram-negative rods SSIs—in some cases procedure- resistance, and costs.8,59,60 and enterococci in addition to skin specific resistance patterns—should The selection of an appropriate flora. Additional details on common take precedence over hospitalwide antimicrobial agent for a specific organisms can be found in procedure- antibiograms. patient should take into account the specific sections of these guidelines. Vancomycin. In 1999, HICPAC, characteristics of the ideal agent, the Recommendations for the selec- an advisory committee to CDC and comparative efficacy of the antimicro- tion of prophylactic antimicrobials the Secretary of the Department of bial agent for the procedure, the safety for various surgical procedures are Health and Human Services, col- profile, and the patient’s medication provided in Table 2. Adult and pe- laborated with other major organiza- allergies. A full discussion of the safety diatric dosages are included in Table tions to develop recommendations profile, including adverse events, drug 1. Agents that are FDA-approved for for preventing and controlling van- interactions, contraindications, and use in surgical antimicrobial prophy- comycin resistance.70 The recom- warnings, for each antimicrobial agent laxis include cefazolin, cefuroxime, mendations are echoed by these and is beyond the scope of these guidelines. cefoxitin, cefotetan, ertapenem, and other guidelines.6,7,41,71 Routine use Readers of these guidelines should vancomycin.62-67 of vancomycin prophylaxis is not review the FDA-approved prescribing Trends in microbiology. The recommended for any procedure.8 information and published data for causative pathogens associated with Vancomycin may be included in the specific antimicrobial agents before SSIs in U.S. hospitals have changed regimen of choice when a cluster of

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MRSA cases (e.g., mediastinitis after general population decreased from pathogen, its antimicrobial suscepti- cardiac procedures) or methicillin- 32.4% in 2001–02 to 28.6% in 2003– bility profile, the host, the procedure resistant coagulase-negative staphy- 04 (p < 0.01), whereas the prevalence to be performed, and the proximity lococci SSIs have been detected at an of colonization with MRSA increased of the likely reservoir of the pathogen institution. Vancomycin prophylaxis from 0.8% to 1.5% (p < 0.05) during to the incision and operative sites. should be considered for patients the same time periods.75 Coloniza- While there is no evidence on the with known MRSA colonization or tion with MRSA was independently management of surgical antimicro- at high risk for MRSA colonization in associated with health care exposure bial prophylaxis in a patient with the absence of surveillance data (e.g., among men, having been born in past infection or colonization with a patients with recent hospitalization, the United States, age of >60 years, resistant gram-negative pathogen, it nursing-home residents, hemodi- diabetes, and poverty among women. is logical to provide prophylaxis with alysis patients).5,41,72 In institutions Similarly, children are colonized with an agent active against MRSA for any with SSIs attributable to community- S. aureus and MRSA, but coloniza- patient known to be colonized with associated MRSA, antimicrobial tion varies by age. Children under 5 this gram-positive pathogen who will agents with known in vitro activity years of age have the highest rates, have a skin incision; specific prophy- against this pathogen may be consid- mirroring rates seen in patients over laxis for a resistant gram-negative ered as an alternative to vancomycin. age 60 years.76 The rates drop in pathogen in a patient with past in- Each institution is encouraged children between 5 and 14 years of fection or colonization with such to develop guidelines for the proper age and gradually increase to rates a pathogen may not be necessary use of vancomycin. Although van- seen in the adult population. Lo et for a purely cutaneous procedure. comycin is commonly used when al.77 reported that in a large cohort of Similarly, a patient colonized with the risk for MRSA is high, data sug- children, 28.1% were colonized with vancomycin-resistant enterococci gest that vancomycin is less effective S. aureus between 2004 and 2006. (VRE) should receive prophylaxis ef- than cefazolin for preventing SSIs Between 2007 and 2009, 23.3% of fective against VRE when undergoing caused by methicillin-susceptible children were colonized with S. au- liver transplantation but probably S. aureus (MSSA).73,74 For this reason, reus, but the proportion of children not when undergoing an umbilical vancomycin is used in combination colonized with MRSA had increased hernia repair without mesh place- with cefazolin at some institutions from 8.1% in 2004 to 15.1% in 2009. ment. Thus, patients must be treated with both MSSA and MRSA SSIs. Surgical antimicrobial prophylaxis on a case-by-case basis, taking into For procedures in which pathogens can alter individual and institutional account multiple considerations. other than staphylococci and strep- bacterial flora, leading to changes Patients receiving therapeutic tococci are likely, an additional agent in colonization rates and increased antimicrobials for a remote infection with activity against those pathogens bacterial resistance.78-84 Surgical pro- before surgery should also be given should be considered. For example, phylaxis can also predispose patients antimicrobial prophylaxis before if there are surveillance data showing to Clostridium difficile-associated surgery to ensure adequate serum that gram-negative organisms are a colitis.81 Risk factors for development and tissue levels of antimicrobials cause of SSIs for the procedure, prac- of C. difficile-associated colitis include with activity against likely pathogens titioners may consider combining longer duration of prophylaxis or for the duration of the operation. If vancomycin with another agent (cef therapy and use of multiple antimicro- the agents used therapeutically are azolin if the patient does not have a bial agents.85 Limiting the duration of appropriate for surgical prophylaxis, b-lactam allergy; an aminoglycoside antimicrobial prophylaxis to a single administering an extra dose within [gentamicin or tobramycin], aztreo- preoperative dose can reduce the risk 60 minutes before surgical incision nam, or single-dose fluoroquinolone of C. difficile disease. is sufficient. Otherwise, the antimi- if the patient has a b-lactam allergy). The question of what antimicro- crobial prophylaxis recommended The use of vancomycin for MRSA bial surgical prophylaxis to use for for the planned procedure should be prophylaxis does not supplant the patients known to be colonized or used. For patients with indwelling need for routine surgical prophylaxis recently infected with multidrug- tubes or drains, consideration may appropriate for the type of proce- resistant pathogens cannot be an- be given to using prophylactic agents dure. When vancomycin is used, it swered easily or in a manner that active against pathogens found in can almost always be used as a single can be applied uniformly to all these devices before the procedure, dose due to its long half-life. patient scenarios. Whether prophy- even though therapeutic treatment Colonization and resistance. A laxis should be expanded to provide for pathogens in drains is not in- national survey determined that coverage for these pathogens de- dicated at other times. For patients S. aureus nasal colonization in the pends on many factors, including the with chronic renal failure receiving

206 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis vancomycin, a preoperative dose of ity reaction that can be caused by bials within 2 hours before surgical cefazolin should be considered in- b-lactam antimicrobials and other incision decreased the risk of SSI to stead of an extra dose of vancomycin, medications.88,89 Patients should be 0.59%, compared with 3.8% for early particularly if the probable patho- carefully questioned about their administration (2–24 hours before gens associated with the procedure history of antimicrobial allergies to surgical incision) and 3.3% for any are gram-negative. In most circum- determine whether a true allergy postoperative administration (any stances, elective surgery should be exists before selection of agents for time after incision).92 In a study of postponed when the patient has an prophylaxis. Patients with allergies to 2048 patients undergoing coronary infection at a remote site. cephalosporins, penicillins, or both bypass graft or valve replacement Allergy to b-lactam antimicrobi- have been excluded from many clini- surgery receiving vancomycin pro- als. Allergy to b-lactam antimicro- cal trials. Alternatives to b-lactam phylaxis, the rate of SSI was lowest in bials may be a consideration in the antimicrobials are provided in Table those patients in whom an infusion selection of surgical prophylaxis. The 2 based mainly on the antimicrobial was started 16–60 minutes before b-lactam antimicrobials, including activity profiles against predominant surgical incision.93 This time interval cephalosporins, are the mainstay of procedure-specific organisms and (16–60 minutes before incision) was surgical antimicrobial prophylaxis available clinical data. compared with four others, and the and are also the most commonly im- rates of SSIs were significantly lower plicated drugs when allergic reac- Drug administration when compared with infusions given tions occur. Because the predominant The preferred route of admin- 0–15 minutes before surgical inci- organisms in SSIs after clean proce- istration varies with the type of sion (p < 0.01) and 121–180 minutes dures are gram-positive, the inclusion procedure, but for a majority of pro- before incision (p = 0.037). The risk of vancomycin may be appropriate cedures, i.v. administration is ideal of infection was higher in patients for a patient with a life-threatening because it produces rapid, reliable, receiving infusions 61–120 minutes allergy to b-lactam antimicrobials. and predictable serum and tissue before incision (odds ratio [OR], Although true Type 1 (immuno- concentrations. 2.3; 95% confidence interval [CI], globulin E [IgE]-mediated) cross- Timing of initial dose. Successful 0.98–5.61) and for patients whose allergic reactions between penicillins, prophylaxis requires the delivery of infusions were started more than 180 cephalosporins, and carbapenems the antimicrobial to the operative site minutes before surgical incision (OR, are uncommon, cephalosporins and before contamination occurs. Thus, 2.1; 95% CI, 0.82–5.62).93 carbapenems should not be used the antimicrobial agent should be In a large, prospective, multi- for surgical prophylaxis in patients administered at such a time to pro- center study from the Trial to Reduce with documented or presumed IgE- vide serum and tissue concentrations Antimicrobial Prophylaxis Errors mediated penicillin allergy. Confu- exceeding the minimum inhibitory (TRAPE) study group, the timing, sion about the definition of true concentration (MIC) for the prob- duration, and intraoperative redosing allergy among patients and practi- able organisms associated with the of antimicrobial prophylaxis and risk tioners leads to recommendations procedure, at the time of incision, and of SSI were evaluated in 4472 patients for alternative antimicrobial therapy for the duration of the procedure.41,90 undergoing cardiac surgery, hyster- with the potential for a lack of ef- In 1985, DiPiro et al.91 demonstrated ectomy, or hip or knee arthroplasty.94 ficacy, increased costs, and adverse that higher serum and tissue cepha- The majority of patients (90%) re- events.86,87 Type 1 anaphylactic reac- losporin concentrations at the time ceived antimicrobial prophylaxis per tions to antimicrobials usually occur of surgical incision and at the end of the SCIP guidelines.41 Patients were 30–60 minutes after administration. the procedure were achieved when assigned to one of four groups for In patients receiving penicillins, this the drugs were given intravenously analysis. Group 1 (n = 1844) received reaction is a life-threatening emer- at the time of anesthesia induction a cephalosporin (or other antimicro- gency that precludes subsequent compared with administration in the bial with a short infusion time) ad- use of penicillins.88 Cephalosporins operating room. The average interval ministered within 30 minutes before and carbapenems can safely be used between antimicrobial administra- incision or vancomycin or a fluoro- in patients with an allergic reaction tion and incision was 17–22 minutes91 quinolone within one hour before to penicillins that is not an IgE- (Dellinger EP, personal communica- incision. Group 2 (n = 1796) received mediated reaction (e.g., anaphylaxis, tion, 2011 May). a cephalosporin 31–60 minutes be- urticaria, bronchospasm) or exfo- A prospective evaluation of 1708 fore incision or vancomycin 61–120 liative dermatitis (Stevens-Johnson surgical patients receiving antimicro- minutes before incision. Group 3 syndrome, toxic epidermal necroly- bial prophylaxis found that preop- (n = 644) was given antimicrobials sis), a life-threatening hypersensitiv- erative administration of antimicro- earlier than recommended, and group

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4 (n = 188) received their initial an- beginning within 30 minutes before than were lower antimicrobial con- timicrobial doses after incision. The surgical incision, these data are not centrations.100 In patients undergo- infection risk was lowest in group 1 sufficiently robust to recommend ing colectomy, infection levels were (2.1%), followed by group 2 (2.4%) narrowing the optimal window to inversely related to the serum gen- and group 3 (2.8%). The risk of infec- begin infusion to 1–30 minutes before tamicin concentration at the time of tion was highest in group 4 (5.3%, surgical incision. However, these data surgical closure.17 In general, it seems p = 0.02 compared with group 1). do suggest that antimicrobials can be advisable to administer prophylactic When cephalosporins and other an- administered too close to the time agents in a manner that will ensure timicrobials with short infusion times of incision. Although a few articles adequate levels of drug in serum and were analyzed separately (n = 3656), have suggested increased infection tissue for the interval during which the infection rate with antimicrobi- risk with administration too close the surgical site is open. als administered within 30 minutes to the time of incision,93,96,97 the data Weight-based dosing. The dosing before incision was 1.6% compared presented are not convincing. In fact, of most antimicrobials in pediatric with 2.4% when antimicrobials were all of these articles confirm the inpatients is based on body weight, but administered 31–60 minutes before creased rate of SSI for antimicrobials the dosing of many antimicrobials in incision (p = 0.13). given earlier than 60 minutes before adults is not based on body weight, In a multicenter Dutch study of incision. In one article, the infection because it is safe, effective, and con- 1922 patients undergoing total hip rate for patients given an antimicro- venient to use standardized doses for arthroplasty, the lowest SSI rate was bial within 15 minutes of incision was most of the adult patient population. seen in patients who received the lower than when antimicrobials were Such standardized doses avoid the antimicrobial during the 30 minutes given 15–30 minutes before incision.97 need for calculations and reduce the before incision.95 The highest risk In another article, small numbers of risk for medication errors. However, for infection was found in patients patients were reported, and an asser- in obese patients, especially those who who received prophylaxis after the tion of high infection rates for infu- are morbidly obese, serum and tissue incision. sion within 15 minutes of incision was concentrations of some drugs may It seems intuitive that the entire made, but no numeric data or p values differ from those in normal-weight antimicrobial dose should be infused were provided.98 In a third article, patients because of pharmacoki- before a tourniquet is inflated or only 15 of over 2000 patients received netic alterations that depend on the before any other procedure that re- antimicrobials within 15 minutes be- lipophilicity of the drug and other stricts blood flow to the surgical site fore incision.93 Earlier studies found factors.101 Limited data are available is initiated; however, a study of total that giving antimicrobials within 20 on the optimal approach to dosing knee arthroplasties compared cefu- minutes of incision and as close as 7 of antimicrobial agents for obese pa- roxime given 10–30 minutes before minutes before incision resulted in tients.102,103 If weight-based dosing is tourniquet inflation with cefuroxime therapeutic levels in tissue at the time warranted for obese patients, it has given 10 minutes before tourniquet of incision.41,90,91,94,97,98 not been determined whether the pa- deflation and found no significant Dosing. To ensure that adequate tient’s ideal body weight or total (i.e., difference in SSI rates between the serum and tissue concentrations of actual) body weight should be used. In two groups.96 antimicrobial agents for prophylaxis theory, using the ideal body weight as Overall, administration of the of SSIs are achieved, antimicrobial- the basis for dosing a lipophilic drug first dose of antimicrobial beginning specific pharmacokinetic and phar- (e.g., vancomycin) could result in sub- within 60 minutes before surgical in- macodynamic properties and patient therapeutic concentrations in serum cision is recommended.41,94,97 Admin- factors must be considered when and tissue, and the use of actual body istration of vancomycin and fluoro- selecting a dose. One of the earliest weight for dosing a hydrophilic drug quinolones should begin within 120 controlled studies of antimicrobial (e.g., an aminoglycoside) could result minutes before surgical incision be- prophylaxis in cardiac surgery found in excessive concentrations in serum cause of the prolonged infusion times a lower rate of infection in patients and tissue. Pediatric patients weigh- required for these drugs. Because with detectable concentrations of the ing more than 40 kg should receive these drugs have long half-lives, this drug in serum at the end of surgery weight-based doses unless the dose or early administration should not com- compared with patients in whom the daily dose exceeds the recommended promise serum levels of these agents drug was undetectable.99 In another adult dose.104 during most surgical procedures. study, higher levels of antimicrobial Conclusive recommendations for Although the recent data summarized in atrial tissue at the time of starting weight-based dosing for antimicrobial above suggest lower infection risk the pump for open-heart surgery prophylaxis in obese patients cannot with antimicrobial administration were associated with fewer infections be made because data demonstrating

208 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis clinically relevant decreases in SSI rates tients with lower BMI values. Tissue Obese patients are often under- from the use of such dosing strategies drug concentrations were lower than represented in clinical trials and are instead of standard doses in obese pa- a targeted concentration of 8 mg/mL not currently considered a special tients are not available in the published at all measurement times, except the population for whom FDA requires literature. time of skin closure in the patients separate pharmacokinetic studies In a small, nonrandomized, two- with the lowest BMIs. These results during antimicrobial research and phase study of morbidly obese suggest that a 1-g dose of cefazolin development by the drug manufac- adults undergoing gastroplasty and may be inadequate for obese patients turer. Obesity has been recognized normal-weight adults undergoing undergoing gastric bypass surgery. as a risk factor for SSI; therefore, upper abdominal surgery, blood and A weakness of the literature on drug optimal dosing of antimicrobial tissue concentrations of cefazolin af- dosing in morbidly obese patients is prophylaxis is needed in these pa- ter the administration of a 1-g preop- the practice of reporting results by tients.114 While a BMI of >30 kg/m2 erative dose were consistently lower BMI rather than weight. is commonly used to define obesity, in morbidly obese patients than in Doubling the normal dose of the body fat percentage (>25% in the normal-weight patients.101 The cephalosporins or making fewer ad- men and >31% in women) may bet- concentrations in morbidly obese justments based on renal dysfunction ter predict SSI risk, because the BMI patients also were lower than the may produce concentrations in obese may not reflect body composition. MICs needed for prophylaxis against patients similar to those achieved In a recent prospective cohort study gram-positive cocci and gram- with standard doses in normal- of 590 patients undergoing elective negative rods. In the second phase of weight patients.103 Considering the surgery, there was no significant dif- the study, adequate blood and tissue low cost and favorable safety profile ference in SSI rates in nonobese and cefazolin concentrations were of cefazolin, increasing the dose to 2 obese patients when the BMI was achieved in morbidly obese patients g for patients weighing more than 80 used to define obesity (12.3% versus receiving preoperative doses of kg and to 3 g for those weighing over 11.6%, respectively).115 However, cefazolin 2 g, and the rate of SSIs was 120 kg can easily be justified.41 For when the body fat percentage (de- significantly lower in these patients simplification, some hospitals have termined by bioelectrical impedance compared with morbidly obese pa- standardized 2-g cefazolin doses for analysis) was used as the basis for tients receiving 1-g doses during the all adult patients. identifying obesity (>25% in men first phase of the study. Gentamicin doses have been com- and >31% in women), obese patients While the optimal cefazolin dose pared for prophylaxis only in colorec- had a fivefold-higher risk of SSI than has not been established in obese tal surgery, where a single dose of did nonobese patients (OR, 5.3; 95% patients, a few pharmacokinetic stud- gentamicin 4.5 mg/kg in combination CI, 1.2–23.1; p = 0.03). These find- ies have investigated the cefazolin with metronidazole was more effective ings suggest that body fat percentage concentrations in serum and tissue in SSI prevention than multiple doses is a more sensitive and precise mea- during surgical procedures.13,105 Two of gentamicin 1.5 mg/kg every eight surement of SSI risk than is the BMI. small pharmacokinetic studies found hours.16,17 In obese patients who weigh Redosing. Intraoperative redosing that administering 1- or 2-g doses 20% above their ideal body weight, the is needed to ensure adequate serum of cefazolin may not be sufficient to dose of gentamicin should be calcu- and tissue concentrations of the produce serum and tissue concentra- lated using the ideal body weight plus antimicrobial if the duration of the tions exceeding the MIC for the most 40% of the difference between the ac- procedure exceeds two half-lives of common pathogens. In a small, single- tual and ideal weights.106 If gentamicin the antimicrobial or there is excessive center study, 38 adults undergoing will be used in combination with a blood loss (i.e., >1500 mL).17,41,94,116-121 Roux-en-Y gastric bypass surgery were parenteral antimicrobial with activity The redosing interval should be mea- classified by body mass index (BMI) against anaerobic agents for prophy- sured from the time of administration in one of three groups.13 All patients laxis, it is probably advisable to use of the preoperative dose, not from the were given cefazolin 2 g i.v. 30–60 min- 4.5–5 mg/kg as a single dose.16 This beginning of the procedure. Redos- utes before the incision, followed by a dose of gentamicin has been found ing may also be warranted if there second 2-g i.v. dose three hours later. safe and effective in a large body of are factors that shorten the half-life The mean serum drug concentration literature examining the use of single of the antimicrobial agent (e.g., ex- before the second dose of cefazolin daily doses of gentamicin for thera- tensive burns). Redosing may not be was lower than the resistance break- peutic indications.106-113 When used warranted in patients in whom the point in all three BMI groups. Serum as a single dose for prophylaxis, the half-life of the antimicrobial agent is drug concentrations were lower in risk of toxicity from gentamicin is prolonged (e.g., patients with renal inpatients with a high BMI than in pa- very low. sufficiency or renal failure). See Table

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1 for antimicrobial-specific redosing (cephalosporin-resistant Enterobac- a smaller, randomized, placebo- recommendations. teriaceae and VRE) compared with controlled study found no difference Duration. The shortest effective short-term prophylaxis (OR, 1.6; between groups.141 duration of antimicrobial administra- 95% CI, 1.1–2.6). More recently, implantable gen- tion for preventing SSI is not known; There are no data to support the tamicin collagen sponges failed to however, evidence is mounting that continuation of antimicrobial pro- show any efficacy in reducing SSIs in postoperative antimicrobial adminis- phylaxis until all indwelling drains a large prospective study of patients tration is not necessary for most pro- and intravascular catheters are undergoing cardiac surgery and cedures.6,7,41,122-124 The duration of an- removed.19,31,32,41,131-134 resulted in an increased infection timicrobial prophylaxis should be less rate in patients undergoing colec- than 24 hours for most procedures. Topical administration of tomy.143,144 The safety and efficacy Cardiothoracic procedures for which a irrigations, pastes, and washes of topical antimicrobials have not prophylaxis duration of up to 48 hours I.V. and oral antimicrobial ad- been clearly established; therefore, has been accepted without evidence ministration are the main focus of routine use of this route cannot be to support the practice is an area that these guidelines, and these routes recommended in cardiac or other remains controversial. The duration of administration are used for most procedures.145 of cardiothoracic prophylaxis in these surgical procedures addressed by guidelines is based on expert panel these guidelines, with the exception Preoperative screening and consensus because the available data of ophthalmic procedures, for which decolonization do not delineate the optimal duration topical administration is the primary S. aureus is the most common of prophylaxis. In these procedures, route of administration. Limited pathogen causing SSIs, accounting prophylaxis for the duration of the high-quality data are available re- for 30% of SSIs in the United States. procedure and certainly for less than garding the use of antimicrobial Colonization with S. aureus, primar- 24 hours is appropriate. irrigations, pastes, and washes that ily in the nares, occurs in roughly one A 1992 meta-analysis of studies are administered topically. Studies in four persons and increases the risk comparing first-generation cepha- published in the early 1980s dem- of SSI by 2- to 14-fold.146-152 A nation- losporins and antistaphylococcal onstrated that prophylactic topical al survey assessing nasal colonization antimicrobials (e.g., penicillins) with administration of antimicrobials in with S. aureus in the general popula- second-generation cephalosporins the surgical incision during various tion conducted from 2001 through in patients undergoing cardiotho- nonophthalmic procedures is supe- 2004 found that while the rate of racic surgery found a reduction in the rior to placebo but not superior to colonization with S. aureus decreased rate of SSI with second-generation parenteral administration, and topi- from 32.4% in 2001–02 to 28.6% in cephalosporins but no benefit from cal administration does not increase 2003–04 (p < 0.01), the rate of colo- continuing surgical prophylaxis be- the efficacy of parenteral antimicro- nization with MRSA increased from yond 48 hours.125 Reports published bials when used in combination for 0.8% to 1.5% (p < 0.05).75 in 1980,126 1993,127 1997,128 and prophylaxis.135-138 Additional high- Preoperative screening for S. aure- 2000129 involving seven studies that quality data on the safety and efficacy us carriage and decolonization strat- compared single-dose prophylaxis of topical antimicrobial administra- egies have been explored as means to or prophylaxis only during the option as an adjunct to i.v. administra- reduce the rate of SSIs. Anterior nasal eration with durations of one to four tion are needed to determine the role swab cultures are most commonly days failed to show any reduction of topical antimicrobial prophylaxis. used for preoperative surveillance, in SSIs with the longer durations of One area of interest for topical but screening additional sites (phar- prophylaxis. In a more-recent obser- administration of antimicrobials, ynx, groin, wounds, rectum) can in- vational four-year cohort study of mainly gentamicin and vancomycin, crease detection rates.153 Such preop- 2641 patients undergoing coronary is application to the sternum during erative surveillance swabs that can be artery bypass graft (CABG) surgery, cardiac procedures in combination cultured on selective or nonselective the extended use of antimicrobial with i.v. agents to prevent mediasti- media or sent for rapid polymerase prophylaxis (>48 hours) instead of nitis. This strategy has been evalu- chain reaction (PCR)-based screen- a shorter duration of prophylaxis ated in cohort and randomized con- ing can be used to identify colonized (<48 hours) failed to reduce the risk trolled studies.139-142 While the studies patients in the preoperative period. of SSI (OR, 1.2; 95% CI, 0.8–1.6).130 found a significantly lower rate of When properly used, all of these Moreover, prolonged prophylaxis SSI with topical antimicrobials com- techniques can identify MSSA and was associated with an increased risk pared with standard prophylaxis,140 MRSA. However, not all PCR-based of acquired antimicrobial resistance placebo,142 and a historical control,139 systems will identify both MRSA

210 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis and MSSA so verification with the aureus SSI among S. aureus carriers before the operation. While S. aureus laboratory is needed. While many (3.7% in the mupirocin group versus resistance to mupirocin has been de- studies have focused specifically on 5.9% in the control group).160 tected,148,162 raising concerns about MRSA screening in high-risk hospi- Another randomized controlled the potential for widespread prob- talized patients in an effort to prevent trial found no significant difference lems with resistance from routine MRSA SSI and hospital-acquired in the rate of postoperative S. aureus use of this agent, resistance has only infections, the risk of developing an SSIs among cardiac surgery patients rarely been seen in the preoperative SSI remains elevated for any S. aureus receiving intranasal mupirocin and setting. Low-level resistance is associ- carrier. While some authors advocate those receiving placebo, but the study ated with an increased rate of failure screening for MRSA carriage in the was limited by the small numbers of of decolonization and has been seen general population, the data sup- patients (n = 257) and reported SSIs in institutions that use standardized porting universal screening in the (n = 5).161 Among elective orthopedic mupirocin decolonization proto- surgical population are more contro- patients undergoing implantation cols.163 Therefore, when decoloniza- versial.154,155 Screening has been advo- and other procedures, a random- tion therapy (e.g., mupirocin) is used cated to both identify candidates for ized clinical trial demonstrated a as an adjunctive measure to prevent S. aureus decolonization and inform nonsignificant reduction in the rate S. aureus SSI, surveillance of suscep- the selection of optimal prophylactic of postoperative S. aureus SSIs in pa- tibility of S. aureus isolated from SSIs antimicrobials, such as the addition tients receiving mupirocin (n = 315, to mupirocin is recommended.164 of vancomycin for those colonized 3.8%) compared with those receiving While universal use of mupirocin is with MRSA. placebo (n = 299, 4.7%).150 discouraged, specific recommenda- FDA has approved intranasal A recent randomized, double- tions for the drug’s use can be found mupirocin to eradicate MRSA nasal blind, placebo-controlled, mul- in the cardiac and orthopedic sec- colonization in adult patients and ticenter study conducted in the tions of these guidelines. health care workers.156 It is noted Netherlands found that the use in the prescribing information that of mupirocin nasal ointment and Future research there are insufficient data to support chlorhexidine baths in identified Additional research is needed in use in prevention of autoinfection S. aureus carriers reduced the risk several areas related to surgical anti- of high-risk patients from their own of hospital-associated S. aureus in- microbial prophylaxis. The risks and nasal colonization with S. aureus. fections.162 In the study, a real-time benefits of continuing antimicrobial However, additional data have dem- PCR assay was used to rapidly iden- prophylaxis after the conclusion of onstrated that the use of intrana- tify S. aureus nasal carriers; all of the the operative procedure, including sal mupirocin in nasal carriers of S. aureus isolates were susceptible dosing and duration, need to be fur- S. aureus decreases the rate of S. aureus to methicillin. Deep SSIs occurred in ther evaluated. Insight is needed to infections.157,158 One meta-analysis of 0.9% of the mupirocin–chlorhexidine- make specific recommendations for seven studies focused on surgical pa- treated group (4 of 441 patients) ver- intraoperative repeat dosing, weight- tients only157; the other meta-analysis sus 4.4% of the placebo group (16 of based dosing in obese patients, and of nine studies included high-quality 367 patients) (relative risk, 0.21; 95% timing of presurgical antimicrobials studies in dialysis patients.158 CI, 0.07–0.62). The reduction in su- that must be administered over a Recent studies have confirmed perficial SSIs was less marked (1.6% prolonged period (e.g., vancomy- that S. aureus decolonization of the versus 3.5%; relative risk, 0.45; 95% cin, fluoroquinolones). Additional anterior nares decreases SSI rates in CI, 0.18–1.11). It is plausible that this clarification is needed regarding many surgical patients.159 The data approach would be beneficial in a targeted antimicrobial concentra- are most compelling in cardiac and setting of MRSA, but it has not been tions and intraoperative monitoring orthopedic surgery patients. There proven. of antimicrobial serum and tissue are fewer data in general surgery Most studies conclude that the use concentrations to optimize efficacy. patients. A large, randomized con- of preoperative intranasal mupirocin The role of topical administration of trolled trial of general, cardiac, and in colonized patients is safe and po- antimicrobial agents as a substitute neurosurgical patients (n = 3864) tentially beneficial as an adjuvant for or an adjunct to i.v. antimicrobial revealed that prophylactic intranasal to i.v. antimicrobial prophylaxis prophylaxis needs to be further eval- application of mupirocin did not to decrease the occurrence of SSIs. uated. Additional data are needed to significantly reduce the overall rate of However, the optimal timing and guide the selection of antimicrobial S. aureus SSIs (2.3% in the mupirocin duration of administration are agents for prophylaxis, particularly group versus 2.4% in the control not standardized. In most studies, combination regimens, for patients group) but did decrease the rate of S. mupirocin was used for five days with allergies to b-lactam antimicro-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 211 ASHP Report Antimicrobial prophylaxis bials. Data are also needed to devise as a bridge to cardiac or lung trans- increased risk of gram-positive SSI strategies to optimize antimicrobial plantation should be treated with in the glycopeptide group but a prophylaxis in patients and facilities a similar approach. If there is no lower frequency of SSIs caused by with a high risk or high prevalence history of colonization or previous resistant gram-positive pathogens.72 of resistant organisms implicated in infection, the general recommen- The routine use of vancomycin SSIs (e.g., MRSA). Optimal strate- dations for SSI antimicrobial pro- for the prevention of SSIs is not gies for screening for S. aureus and phylaxis for the specific procedure recommended, based on limited decolonization for certain proce- should be followed. For ECMO pa- evidence of efficacy and concerns of dures need to be identified. Finally, tients with a history of colonization increased glycopeptide resistance of outcomes studies are needed to assess or previous infection, changing the microorganisms.8,116 There is no clear the impact of using quality measures preoperative antimicrobial prophy- evidence to support the use of vanco- and pay-for-performance incentives laxis to cover these pathogens must mycin, alone or in combination with designed to reduce surgical morbid- be considered, weighing whether the other antimicrobials, for routine ity and mortality. pathogen is relevant to SSIs in the antimicrobial prophylaxis in institu- planned procedure. tions that have a high prevalence Cardiac procedures Organisms. Almost two thirds of MRSA.8,11,41,72,73,116,200 Vancomycin Background. Cardiac procedures of organisms isolated in both should be considered in patients who include CABG procedures, valve re- adult and pediatric patients un- are colonized with MRSA.41,116,201 pairs, and placement of temporary dergoing cardiac procedures are The accepted alternative antimicro- or permanent implantable cardiac gram-positive, including S. aureus, bial for b-lactam-allergic patients devices, including ventricular assist coagulase-negative staphylococcus, undergoing cardiac procedures is devices (VADs). SSIs, including medi- and, rarely, Propionibacterium acnes. vancomycin or clindamycin for gram- astinitis and sternal wound infection, Gram-negative organisms are less positive coverage.41,116,201,202 The ad- are rare but serious complications commonly isolated in these patients dition of an aminoglycoside, aztreo- after cardiac procedures. In patients and include Enterobacter species, nam, or a fluoroquinolone may be undergoing CABG, the mean fre- Pseudomonas aeruginosa, Escherichia prudent when gram-negative patho- quency of SSIs depending on NHSN coli, Klebsiella pneumoniae, Pro- gens are a concern.8,116 SSI risk index category ranges from teus mirabilis, and Acinetobacter Mupirocin. The proportion of 0.35 to 8.49 per 100 operations when species.93,139,146,183-192 infections related to S. aureus among donor sites are included.165 The Efficacy. The SSI rate in cardiac patients undergoing cardiac surgery mean frequency of SSIs depending procedures is low, but there are po- and the increase in MRSA as a cause on NHSN SSI risk index category tential consequences if infection of SSIs at some institutions have for patients undergoing CABG with occurs. Multiple studies have found led to investigations of methods for only chest incisions ranges from 0.23 that antimicrobial prophylaxis in car- preoperative eradication, particu- to 5.67 per 100 operations.165 Most diac procedures lowers the occurrence larly with intranasal mupirocin.203 of these infections are superficial in of postoperative SSI up to fivefold.125 Readers are referred to the Common depth. Patient-related and procedure- Choice of agent. Cephalosporins Principles section of these guidelines related risk factors for SSIs after car- have been the most studied antimi- for discussion of the use of intranasal diac procedures have been identified crobials for the prevention of SSIs mupirocin. Of note, the data dem- from several single-center cohort and in cardiac procedures. Both first- onstrated a 45% reduction in S. au- case–control studies.117,128,166-176 These generation (cefazolin) and second- reus SSIs with the use of preoperative include diabetes,166,169,171-175 hypergly- generation (cefamandole and cefu- mupirocin among patients known cemia,177-182 peripheral vascular dis- roxime) cephalosporins have been to be colonized with S. aureus who ease,171,172,174 chronic obstructive pul- shown to be effective in reducing undergo cardiac procedures.157,193 monary disease,166,174,175 obesity (BMI SSI in cardiac surgery; however, the Institutions should monitor for mu- of >30 kg/m2),166-168,171,173-176 heart superiority of one class over another pirocin resistance periodically. failure,171,172 advanced age,117,128,166,172 has not been proven.125,127,193-199 Topical administration. Additional involvement of internal mammary ar- A meta-analysis comparing ceph- information on topical administra- tery,168-172 reoperation,169-171 increased alosporins with glycopeptides (e.g., tion of antimicrobials can be found number of grafts,171 long duration of vancomycin) as antimicrobial pro- in the Common Principles section surgery,117,166,167,176 and S. aureus nasal phylaxis regimens for cardiac proof these guidelines. Use of topical colonization.146,160 cedures found a higher frequency antimicrobials, mainly gentamicin or Patients requiring extracorporeal of postoperative chest and deep- vancomycin, applied to the sternum membrane oxygenation (ECMO) chest SSIs and a trend toward an during cardiac procedures in com-

212 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis bination with i.v. agents to prevent gested the possibility of increased risk score of 2, and the performance of mediastinitis has been evaluated in efficacy with cardiac surgical pro- emergency procedures.20,31,221 both cohort139 and randomized con- phylaxis extending beyond 24 hours, The organisms of concern in trolled studies.140-142 While the stud- the authors noted that the findings pediatric patients are the same as ies found a significantly lower rate were limited by the heterogeneity of those in adult patients.20,21,31,221 How- of SSIs with topical antimicrobials antimicrobial regimens used and the ever, MRSA is rarely a concern in compared with standard prophy- risk of bias in the published stud- this population as a risk factor for laxis,140 placebo,142 and a historical ies.218 The comparisons of varying SSI.221 Pediatric patients considered control,139 a smaller randomized, durations were performed with dif- at high risk for MRSA infection placebo-controlled study found no ferent antimicrobials with differing are those with preoperative MRSA difference between groups.141 More efficacy and do not support longer colonization or a history of MRSA recent studies of gentamicin collagen durations. Consequently, this meta- infection, neonates younger than one sponges failed to show any efficacy in analysis does not provide evidence month of age, and neonates under a large prospective study of cardiac to support changing the currently three months of age who have been surgery.143 The safety and efficacy of accepted prophylaxis duration of in the hospital since birth or have a topical antimicrobials have not been less than 24 hours, particularly given complex cardiac disorder.21 Strategies clearly established and therefore can- the evidence from studies involving such as intranasal mupirocin and not be recommended for routine use noncardiac operations. The currently changes in antimicrobial prophylac- in cardiac procedures.139-142 accepted duration of prophylaxis tic agent to vancomycin led to de- Cardiopulmonary bypass. Cardio- for cardiac procedures is less than creased rates of MRSA carriage and pulmonary bypass (CPB) is a com- 24 hours, but prophylaxis should be the absence of MRSA infections in mon surgical technique in cardiac continued for the duration of the one time-series evaluation; however, procedures that alters the volume procedure.41,59,126-129,131,201 the overall clinical impact of these of distribution and bioavailability Two small studies did not support efforts is still unclear.21,221 of medications administered during the continuation of antimicrobial No well-controlled studies have the procedure.116,204,205 Several small prophylaxis until intravascular cath- evaluated the efficacy of antimicro- cohort or comparative studies128,204-213 eters or intraaortic balloon pumps bial prophylaxis in pediatric patients have evaluated the serum and tissue were removed, due to a lack of influ- undergoing cardiac procedures. concentrations of several routinely ence on infections or catheter coloni- Therefore, the efficacy of antimi- used antimicrobial prophylactic zation compared with short-course crobial prophylaxis is extrapolated agents (i.e., cefazolin, cefuroxime, (24 hours) cefazolin or cefurox- from adult studies and should be gentamicin, and vancomycin) in ime.219,220 The practice of continuing considered the standard of care for patients undergoing CPB during antimicrobial prophylaxis until all pediatric cardiac surgery patients.19 cardiac procedures. Until further invasive lines, drains, and indwell- No well-designed studies or con- clinical outcomes data and well- ing catheters are removed cannot be sensus has established the appropri- designed studies become available to supported due to concerns regarding ate doses for common antimicrobial inform alternative dosing strategies, the development of drug-resistant prophylactic agents for use in pediat- routinely used doses of common organisms, superinfections, and drug ric cardiac patients. Antibiotic doses antimicrobial agents should be used toxicity.41,131 have been extrapolated from guide- in patients undergoing CPB during Pediatric efficacy. The rate of SSI lines for the prevention of bacterial cardiac procedures. in pediatric cardiac procedures is endocarditis.11 In recent evaluations, Duration. The optimal duration sometimes higher than in adult pa- doses of cefazolin have ranged from of antimicrobial prophylaxis for tients.20,31,221 Significant risk factors in 25 to 50 mg/kg,19-21,31 and vancomy- cardiac procedures continues to be pediatric patients with a mediastinal cin doses have ranged from 10 to 20 evaluated. Data support a duration SSI included the presence of other in- mg/kg.19-21,31,222-226 Gentamicin doses ranging from a single dose up to 24 fections at the time of the procedure, used in studies have included 2.520 hours postoperatively.41,99,131,191,214-217 young age (newborns and infants), and 5 mg/kg22; however, the study No significant differences were found small body size, the duration of the authors22 felt that the higher dose in several small studies in patients procedure (including CPB time), was excessive. The expert panel rec- undergoing cardiac procedures be- the need for an intraoperative blood ognizes that the usual total daily dose tween these dosing strategies in transfusion, an open sternum postop- for pediatric patients older than six patients primarily receiving first- or eratively, the need for a reexploration months can be 6.5–7.5 mg/kg and second-generation cephalosporins. procedure, the length of stay in the that dosing schedules for younger Although a recent meta-analysis sug- intensive care unit, an NNIS/NHSN patients may be complicated.

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Recommendations. For patients tation, temporary pacing before im- cardioverter defibrillator, or cardiac undergoing cardiac procedures, the plantation, and early reintervention resynchronization device in a surgi- recommended regimen is a single for hematoma or lead replacement230; cal operating room.231 The expert preincision dose of cefazolin or corticosteroid use for more than one panel noted that the cefazolin dose cefuroxime with appropriate intra- month during the preceding year was not adjusted for patient weight. operative redosing (Table 2). Cur- and more than two leads in place Recently, AHA produced evidence- rently, there is no evidence to sup- compared with two leads232; and de- based guidelines that recommend the port continuing prophylaxis until velopment of pocket hematoma.231 In use of a single dose of a preoperative all drains and indwelling catheters all of the evaluations, antimicrobial antimicrobial.229 are removed. Clindamycin or vanco- prophylaxis was found to be protec- VADs are increasingly used to mycin is an acceptable alternative in tive against device-related infec- bridge patients to transplantation patients with a documented b-lactam tion.230-232 Limited data are available or to support individuals who do allergy. Vancomycin should be used on the efficacy and optimal dose and not respond to medical therapy for for prophylaxis in patients known duration of antimicrobial prophylaxis congestive heart failure. Very lim- to be colonized with MRSA. If or- in patients undergoing implantation ited data exist on infection rates, ganizational SSI surveillance shows of a new pacemaker, pacing system, or and there are no published studies that gram-negative organisms cause other cardiac device. that demonstrate the effectiveness of infections for patients undergoing A meta-analysis of 15 prospective, preoperative antimicrobial therapy. these operations, practitioners should randomized, controlled, mainly open- Using 2006–08 data from the In- combine clindamycin or vancomycin label studies evaluated the effective- teragency Registry for Mechani- with another agent (cefazolin if the ness of systemic antimicrobial pro- cally Assisted Circulatory Support, patient is not b-lactam allergic; az- phylaxis compared with controls (no Holman and colleagues234 reported treonam, aminoglycoside, or single- antimicrobials) on infection rates that most infections related to me- dose fluoroquinolone if the patient is after pacemaker implantation.227 chanical cardiac support devices b-lactam allergic). Mupirocin should Antibiotics included penicillins or were bacterial (87%), with the re- be given intranasally to all patients cephalosporins with a duration mainder associated with fungal (9%), with documented S. aureus coloniza- ranging from a single preoperative viral (1%), protozoal (0.3%), or un- tion. (Strength of evidence for pro- dose to four days postoperatively. A known (2%) causes. Driveline infec- phylaxis = A.) consistent and significant protective tions are primarily caused by staphy- effect of antimicrobial prophylaxis lococcal species from the skin. Fungal Cardiac device insertion was found and encouraged the rou- organisms also play an important procedures tine use of antimicrobial prophylaxis role in VAD infections, most notably Background. Antimicrobial pro- in patients undergoing permanent Candida species, and carry a high risk phylaxis is the standard of care for pacemaker implantation. A prospec- of mortality. A recent survey of anti- patients undergoing cardiac implant- tive, single-center cohort study found microbial surgical prophylaxis with able device insertion (e.g., pacemaker a low rate (1.7%) of SSI complications VADs illustrates the variability and implantation).227 Based on available with a single 2-g dose of cefazolin in lack of consensus with regimens, us- data and perceived infection risk, patients undergoing implantation of ing anywhere from one to four drugs antimicrobial prophylaxis is not a new pacemaker, pulse-generator for a duration of 24–72 hours.235 Im- routinely recommended for cardiac replacement, or upgrading of a pre- mediate postoperative infections are catheterization or transesophageal existing pacing system.233 A notable caused by gram-positive organisms. echocardiogram.228 limitation of the study was the ex- Complications from long-term in- NHSN has reported a mean SSI clusion of patients with temporary fections should not be confused with rate after pacemaker placement of percutanous cardiac stimulators who immediate postprocedure SSIs.236 0.44 per 100 procedures.165 This rate are at high risk of infection. Based on the consensus of the expert may underestimate the risk of late A large, randomized, double- panel, antimicrobial prophylaxis for SSI and complications.229 Risk fac- blind, placebo-controlled study replacement of a VAD due to ongo- tors for device-related infection found a significantly lower rate ing or recent infection should in- after implantation of cardioverter– of SSI with a single 1-g dose of corporate coverage directed at the defibrillator systems or pacemakers cefazolin (0.64%) compared with offending organism or organisms. identified in two large, prospective, placebo (3.28%) (p = 0.016) given While many centers use vancomycin multicenter cohort studies230,231 and immediately before device implanta- plus ciprofloxacin plus fluconazole, a large case–control study232 included tion or generator replacement in a this practice is not based on the pub- fever within 24 hours before implan- permanent pacemaker, implantable lished evidence.

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Recommendation. A single dose study of 988 lung resection patients ing the esophagus and exploratory of cefazolin or cefuroxime is rec- confirmed that the SSI rate was thoracotomies, compared a single ommended for device implanta- significantly lower (5.5%) in VATS dose of cefazolin 1 g i.v. and placebo tion or generator replacement in a patients than in open thoracotomy given 30 minutes before the proce- permanent pacemaker, implantable patients (14.3%).247 Furthermore, SSI dure.239 The study was stopped early cardioverter defibrillator, or cardiac correlated with the duration of sur- due to the significant difference in resynchronization device. (Strength gery, serum albumin, concurrent co- SSI rates between groups (1.5% with of evidence for prophylaxis = A.) morbidity, age, and forced expiratory cefazolin versus 14% with placebo, There is limited evidence to make volume in one second. Antimicrobial p < 0.01). No differences in the rates specific recommendations for VADs, prophylaxis recommendations in this of pneumonia and empyema were and each practice should tailor pro- section refer to both open thora- seen between groups, but these were tocols based on pathogen prevalence cotomy and VATS procedures. Based not endpoints of the study. and local susceptibility profiles. on available data and perceived infec- Choice of agent. There is no clear Clindamycin or vancomycin is an tion risk, antimicrobial prophylaxis is optimal choice for antimicrobial acceptable alternative in patients not routinely recommended for chest prophylaxis in thoracic procedures. with a documented b-lactam allergy. tube insertion. The need to consider pneumonia and Vancomycin should be considered Results of a prospective cohort empyema as well as SSIs after thorac- for prophylaxis in patients known to and case–control study revealed the ic procedures has been raised in the be colonized with MRSA. following independent risk factors literature.237,241-244 There are a limited for pneumonia after thoracic pro- number of small, single-center, ran- Thoracic procedures cedures: extent of lung resection, domized controlled or cohort studies Background. Noncardiac tho- intraoperative bronchial coloniza- that evaluated several antimicrobial racic procedures include lobectomy, tion, chronic obstructive pulmonary agents. One small, randomized con- pneumonectomy, thoracoscopy, lung disease, BMI of >25 kg/m2, induction trolled study and one cohort study resection, and thoracotomy. In addi- therapy (chemotherapy, radiothera- found that ampicillin–sulbactam tion to SSIs, postoperative nosoco- py, or chemoradiotherapy), advanced was significantly better than cephalo- mial pneumonia and empyema are of age (≥75 years old), and stage III or sporins (cefazolin and cefamandole) concern after thoracic procedures.237 IV cancer.243,244 for preventing pneumonia.242,243 No NHSN has reported that the rate Organisms. The organisms re- statistically significant difference of infection associated with tho- ported from SSIs in patients un- was found between cefuroxime and racic surgery ranges from 0.76% to dergoing thoracic procedures were cefepime in the rate of postoperative 2.04%.165 Studies have found that the S. aureus and S. epidermidis.237 SSI, pneumonia, or empyema in a reported rate of SSIs after thoracic Organisms isolated in patients with small, randomized controlled study procedures in patients receiving an- postoperative pneumonia includ- in patients undergoing elective tho- timicrobial prophylaxis ranged from ed gram-positive (Streptococcus racotomy.241 Lower rates of infections 0.42% to 4%.238-241 One study found and Staphylococcus species), gram- and susceptibility of all organisms an SSI rate of 14% when prophylaxis negative (Haemophilus influenzae, were noted with cefuroxime com- was not used.239 The reported rates of Enterobacter cloacae, K. pneumoni- pared with cefepime. Therefore, the pneumonia and empyema with anti- ae, Acinetobacter species, P. aeru- study authors concluded that cefu- microbial prophylaxis are 3–24% and ginosa, and Moraxella catarrha- roxime was marginally more effective 0–7%, respectively.237,239-244 lis), and fungal (Candida species) and was more cost-effective than Video-assisted thoracoscopic sur- pathogens.237,239-243 cefepime. gery (VATS) is commonly used for Efficacy. Antimicrobial prophy- Duration. No clear consensus thoracic procedures. In some set- laxis is the standard of care for on the duration of antimicrobial tings, VATS constitutes one third or patients undergoing noncardiac tho- prophylaxis has been established. more of all thoracic surgical proce- racic surgery, including pulmonary Studies have evaluated different dos- dures.245 Since VATS uses small inci- resection.11,201,237 One randomized, ing strategies for cephalosporins or sions, the rate of SSIs is lower com- double-blind, placebo-controlled, penicillins, with most studies using pared with the rate associated with single-center study of patients in single doses given preoperatively open thoracic surgical procedures.246 Spain undergoing pulmonary resec- within 60 minutes before surgical A prospective cohort study (n = 346) tion, persistent pneumothorax with- incision.237,239,240,242,244 Studies found confirmed a low rate of SSIs (1.7%) out thoracotomy tube before surgery, differing results when comparing after minimally invasive VATS pro- and nonpulmonary thoracic surgical agents given for 24 hours (cefepime, cedures.240 An additional prospective procedures, excluding those involv- ampicillin–sulbactam) and 48 hours

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(cefuroxime, cefamandole); how- could not be identified. Antireflux motility, gastric outlet obstruction, ever, these findings may be attribut- procedures and highly selective morbid obesity, gastric bleeding, or able to the different antimicrobials vagotomy are clean procedures in cancer.265 Similar to other types of tested.241,243 Additional discussion on contrast to essentially all other gas- surgical procedures, risk factors for dosing is provided in the Common troduodenal procedures that are SSIs related to gastroduodenal proce- Principles section of these guidelines. clean-contaminated. Other procedures include long procedure dura- Recommendations. In patients dures that are generally performed tion,252,266,267 performance of emer- undergoing thoracic procedures, a using laparoscopic or endoscopic gency procedures,250,261 greater than single dose of cefazolin or ampicillin– techniques (e.g., endoscopic retro- normal blood loss,251,252 American sulbactam is recommended (Appen- grade cholangiopancreatography) Society of Anesthesiologists (ASA) dix B). Clindamycin or vancomycin are not specifically discussed in this classification of≥ 3, and late adminis- is an acceptable alternative in pa- document. Natural orifice translu- tration of antimicrobials.268 tients with a documented b-lactam minal endoscopic surgery (NOTES) Organisms. The most common allergy. Vancomycin should be used is a developing operative technique organisms cultured from SSIs af- for prophylaxis in patients known using natural orifices (e.g., vagina, ter gastroduodenal procedures are to be colonized with MRSA. If or- anus, mouth, stomach) for entry into coliforms (E. coli, Proteus species, ganizational SSI surveillance shows the abdomen that leaves no visible Klebsiella species), staphylococci, that gram-negative organisms are as- scar.248 No studies on antimicrobial streptococci, enterococci, and oc- sociated with infections during these prophylaxis using NOTES have been casionally Bacteroides species.101,269-276 operations or if there is risk of gram- published. SSI rates reported in pa- Efficacy. Randomized controlled negative contamination of the surgi- tients not receiving antimicrobial trials have shown that prophylactic cal site, practitioners should combine prophylaxis were 6% after vagotomy antimicrobials are effective in de- clindamycin or vancomycin with an- and drainage, 13% after gastric ulcer creasing postoperative infection rates other agent (cefazolin if the patient procedures, 6.8–17% after proce- in high-risk patients after gastroduo- is not b-lactam allergic; aztreonam, dures for gastric cancer,249-253 8% for denal procedures. The majority of aminoglycoside, or single-dose fluo- pancreaticoduodenectomy,254 and available studies were conducted in roquinolone if the patient is b-lactam 23.9–26% after PEG insertion.255,256 single centers outside of the United allergic). (Strength of evidence for The stomach is an effective bar- States. Relative to other types of prophylaxis for VATS = C; strength rier to bacterial colonization; this is at gastrointestinal tract procedures, the of evidence for prophylaxis for other least partially related to its acidity. The number of clinical trials evaluating thoracic procedures = A.) stomach and the duodenum typically antimicrobial prophylaxis for gastro- contain small numbers of organisms duodenal procedures is limited. In Gastroduodenal procedures (<104 colony-forming units [CFU]/ placebo-controlled trials, infection Background. The gastroduode- mL), the most common of which are rates ranged from 0% to 22% for nal procedures considered in these streptococci, lactobacilli, diphtheroids, patients receiving cephalosporins guidelines include resection with and fungi.257,258 Treatment with agents or penicillins and from 1.7% to or without vagotomy for gastric or that increase gastric pH increases 66% for patients receiving place- duodenal ulcers, resection for gas- the concentration of gastric organ- bo.270,271,273-275,277-284 The difference was tric carcinoma, revision required to isms.259-261 Alterations in gastric and significant in most studies. repair strictures of the gastric outlet, duodenal bacterial flora as a result of Data support antimicrobial pro- percutaneous endoscopic gastros- increases in gastric pH have the po- phylaxis for patients undergoing tomy (PEG) insertion, perforated tential to increase the postoperative PEG insertion.264,285-287 A Cochrane ulcer procedures (i.e., Graham patch infection rate.262,263 review of systemic antimicrobial repair), pancreaticoduodenectomy The risk of postoperative infec- prophylaxis for PEG procedures that (Whipple procedure), and bariatric tion in gastroduodenal procedures included 11 randomized controlled surgical procedures (gastric bypass, depends on a number of factors, trials and 1196 patients found a gastric banding, gastroplasty, other including the gastroduodenal pro- statistically significant reduction in restrictive procedures, biliopancre- cedure performed. Patients who are peristomal infections with antimi- atic diversion). Studies specifically at highest risk include those with crobial prophylaxis (OR, 0.35; 95% addressing antimicrobial prophylaxis achlorhydria, including those receiv- CI, 0.23–0.48).288 Two meta-analyses for gastroesophageal reflux disease ing pharmacotherapy with histamine found statistically significant de- procedures (Nissen fundoplication) H2-receptor antagonists or proton- creases in SSIs with antimicrobial or highly selective vagotomy for ul- pump inhibitors,264 gastroduode- prophylaxis compared with place- cers (usually done laparoscopically) nal perforation, decreased gastric bo or controls, from 23.9–26% to

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6.4–8%, respectively.255,256 Most well- Furthermore, laparoscopic antireflux ciprofloxacin or gentamicin was the designed, randomized controlled procedures are associated with very most active regimen against bacteria studies found a significant decrease low SSI rates (0.3%) compared with recovered from bile in pancreatoduo- in postoperative SSIs or peristomal open antireflux procedures (1.4%), denectomy patients.302 infections with single i.v. doses of a just as laparoscopic gastric bypass Duration. The majority of studies cephalosporin or penicillin, ranging procedures are associated with lower evaluated a single dose of cephalo- from 11% to 17%, compared with rates than in open procedures (0.4% sporin or penicillin.256,279-284,288,290,297 from 18% to 66% with placebo or versus 1.2%).292 The available data indicate that no antimicrobials.279-282,288 Conflict- Choice of agent. The most single-dose and multiple-dose regi- ing results have been seen in studies frequently used agents for gastro- mens are similarly effective. Three evaluating the use of preoperative duodenal procedures were first- studies compared single- and mul- patient MRSA screening, decontami- generation271,273,277,278,284,293-297 and sec- tiple-dose regimens of cefaman- nation washes and shampoos, five- ond-generation269,270,274,275,280,293,294,298 dole,294 amoxicillin–cluvulanate,299 day preoperative treatment with in- cephalosporins. No differences in and ampicillin–sulbactam and ce- tranasal mupirocin, and single-dose efficacy between first- and second- fazolin.253 There were no significant teicoplanin preoperative prophylaxis generation cephalosporins were differences in SSI rates. Multiple-dose to decrease postoperative MRSA in- found. Amoxicillin–clavulanate regimens of first-generation (cefazo- fections during PEG insertion.289,290 279,282,283,299 and ciprofloxacin269,300 were lin) or second-generation (cefotiam) While there have been no well- also evaluated with similar results. cephalosporins of four days, operative designed clinical trials of antimicro- Relatively few studies have compared day only, and three days in duration bial prophylaxis for patients under- the efficacy of different agents in re- did not differ in overall SSI rates.295 going bariatric surgical procedures, ducing postoperative infection rates. Recommendations. Antimicrobial treatment guidelines support its use One meta-analysis recommended prophylaxis in gastroduodenal pro- based on morbid obesity and ad- using a single dose of an i.v. broad- cedures should be considered for pa- ditional comorbidities as risk factors spectrum antimicrobial for SSI tients at highest risk for postoperative for postoperative infections.264,291 prophylaxis in these patients,256 infections, including risk factors such There is no consensus on the appro- while another found no differences as increased gastric pH (e.g., patients priate antimicrobial regimen; how- between penicillin- or cephalosporin- receiving acid-suppression therapy), ever, higher doses of antimicrobials based regimens and three-dose or gastroduodenal perforation, de- may be needed for adequate serum single-dose regimens.255 In a com- creased gastric motility, gastric outlet and tissue concentrations in mor- parative study, oral or i.v. ciprofloxa- obstruction, gastric bleeding, morbid bidly obese patients.13,268,291 cin and i.v. cefuroxime were similarly obesity, ASA classification of≥ 3, and A notable risk factor for SSIs effective in upper gastrointestinal cancer. after esophageal and gastroduode- procedures, including gastrectomy, A single dose of cefazolin is rec- nal procedures is decreased gastric vagotomy, and fundoplication.300 No ommended in procedures during acidity and motility resulting from differences in efficacy were seen be- which the lumen of the intestinal malignancy or acid-suppression tween ceftriaxone and combination tract is entered (Table 2). (Strength of therapy.264,276 Therefore, antimicro- ceftriaxone and metronidazole for evidence for prophylaxis = A.) A sin- bial prophylaxis is indicated for pa- PEG insertion in pediatric patients.301 gle dose of cefazolin is recommended tients undergoing gastric cancer pro- An open-label study found a signifi- in clean procedures, such as highly cedures (including gastrectomy) and cant decrease in local peristomal and selective vagotomy, and antireflux gastroduodenal procedures related to systemic infection (i.e., pneumonia) procedures only in patients at high gastric and duodenal ulcer disease or after PEG insertion after a single 1-g risk of postoperative infection due to bariatric surgery or pancreaticoduo- i.v. dose of ceftriaxone was given the presence of the above risk factors. denectomy. Evaluations of practice 30 minutes before surgery when (Strength of evidence for prophylaxis for pancreaticoduodenectomy show compared with placebo (13.3% and = C.) Alternative regimens for pa- that antimicrobials are typically giv- 36.3%, respectively; p < 0.05).281 tients with b-lactam allergy include en due to concerns of bile contami- No differences were noted be- clindamycin or vancomycin plus nation. Prophylaxis for gastroduode- tween cefotaxime and piperacillin– gentamicin, aztreonam, or a fluoro- nal procedures that do not enter the tazobactam for PEG SSIs.288 quinolone. Higher doses of antimi- gastrointestinal tract, such as antire- Ampicillin–sulbactam and cefazolin crobials are uniformly recommended flux procedures, should be limited to had equal efficacy in gastrectomy.253 in morbidly obese patients undergo- high-risk patients due to lack of data One study found that piperacillin– ing bariatric procedures. Higher dos- supporting general use in all patients. tazobactam in combination with es of antimicrobials should be con-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 217 ASHP Report Antimicrobial prophylaxis sidered in significantly overweight Risk factors associated with post- the optimal antimicrobials for SSI patients undergoing gastroduodenal operative SSIs after biliary procedures prevention in biliary tract procedures. and endoscopic procedures. include performance of emergency Efficacy. Numerous studies have procedures,305 diabetes,305,306,311,315,317 evaluated the use of prophylac- Biliary tract procedures longer procedure duration (over tic antimicrobials during biliary Background. Biliary tract pro- 120 minutes),305,317,324 intraoperative tract procedures, with a focus on cedures include cholecystectomy, gallbladder rupture,305 age of >70 laparoscopic cholecystectomy. Lapa- exploration of the common bile duct, years,6,311,315,317,325 open cholecystecto- roscopic cholecystectomy has re- and choledochoenterostomy. These my,7,311 conversion of laparoscopic to placed open cholecystectomy as guidelines pertain only to patients open cholecystectomy,7 higher ASA the standard of practice because of undergoing biliary tract procedures classification ≥( 3),306,310,317 episode of the reduction in recovery time and with no evidence of acute biliary biliary colic within 30 days before the shorter hospital stay. The majority of tract infection and to patients with procedure,315,316 reintervention in less studies of antimicrobial prophylaxis community-acquired acute cholecys- than a month for noninfectious com- for laparoscopic cholecystectomy titis of mild-to-moderate severity. As plications,310 acute cholecystitis,6,7,306 were underpowered and varied in noted in the Common Principles sec- bile spillage,7 jaundice,6,7,306 preg- control groups used (placebo, active, tion, patients receiving therapeutic nancy,7 nonfunctioning gallbladder,6 or no treatment), follow-up (from antimicrobials for an infection before and immunosuppression.7 30 to 60 days, while some stud- surgery should be given additional The biliary tract is usually sterile. ies did not clearly define length of antimicrobial prophylaxis before Patients with bacteria in the bile time), and how SSIs were detected surgery. at the time of surgery may be at and reported.308,312-316,318,319,321,322 Some These guidelines do not address higher risk of postoperative infec- studies included patients who were patients requiring biliary tract pro- tion305,326,327; however, some studies converted from laparoscopic to open cedures for more-severe infections, have found no association between cholecystectomy and others did not. including community-acquired the presence of bacteria in the bile A large, multicenter, quality- acute cholecystitis with severe phys- and infection.305,315,316,319,321 Obesity assurance study in Germany assessed iological disturbance, advanced (a BMI of >30 kg/m2) was found to the effectiveness of antimicrobial age, or immunocompromised state; be a risk factor in some studies306 prophylaxis in laparoscopic and open acute cholangitis; and health-care- but not in others.315,319 Laparoscopic cholecystectomies.308 This study in- associated or nosocomial biliary cholecystectomy was associated cluded 4477 patients whose antimi- infections. These biliary tract infec- with a significantly decreased risk for crobial choice and dosage regimens tions are treated as complicated SSI.292,310,324,325 were at the discretion of the medical intraabdominal infections.303 All Organisms. The organisms most center and surgeon. Antimicrobials patients with a suspected biliary tract commonly associated with infec- used included first-, second-, and infection who undergo biliary tract tion after biliary tract procedures third-generation cephalosporins or surgery should receive preoperative include E. coli, Klebsiella species, penicillins alone or in combination i.v. antimicrobials. and enterococci; less frequently, with metronidazole, gentamicin, or The majority of published lit- other gram-negative organisms, both metronidazole and gentamicin. erature regarding SSIs in biliary tract streptococci, and staphylococci are The most common cephalosporin procedures focuses on cholecystecto- isolated.305,306,312,315,316,318,319,321,326,328-338 used was ceftriaxone, allowing its my. The overall reported rate of post- Anaerobes are occasionally reported, data to be separated from data for operative infection in open biliary most commonly Clostridium species. other antimicrobials. Antimicro- tract procedures with antimicrobial Recent studies have documented bial prophylaxis was administered to prophylaxis is 1–19%.292,304-311 Infec- increasing antimicrobial resistance 2217 patients (ceftriaxone [n = 787 tion rates after laparoscopic chole- in the causative pathogens in biliary laparoscopic and n = 188 open] and cystectomy range from 0% to ap- tract infections and other intra- other antimicrobials [n = 229 lapa- proximately 4% in patients without abdominal infections, with up to roscopic and n = 229 open]); none antimicrobial prophylaxis308,312-320 40% of E. coli isolates resistant to was given to 1328 laparoscopic and and from 0% to 7% with prophy- ampicillin–sulbactam and fluoro- 932 open cholecystectomy patients. laxis.292,304-323 Several studies found quinolones.339-341 Due to this increas- Significantly lower overall infectious that laparoscopic cholecystectomy ing resistance of E. coli to fluoroquin- complications occurred in patients SSI rates were significantly lower olones and ampicillin–sulbactam, receiving antimicrobial prophylaxis than those associated with open local population susceptibility pro- (0.8% ceftriaxone and 1.2% other cholecystectomy.292,306-311 files should be reviewed to determine antimicrobials), compared with 5%

218 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis of those who received no prophylaxis cholecystitis, common bile duct cal- Current data do not support (p < 0.05). The overall rates of infec- culi, jaundice, immune suppression, antimicrobial prophylaxis for low- tious complications were 0.6%, 0.8%, and prosthetic implants. A total of risk patients undergoing elective and 3.3% in patients undergoing 2961 patients were enrolled in the laparoscopic cholecystectomies or laparoscopic cholecystectomy receiv- studies, including 1494 who received those with incidental or accidental ing ceftriaxone, other antimicrobials, antimicrobial prophylaxis, primar- gallbladder rupture. Antimicrobial and no prophylaxis, respectively, and ily with cephalosporins, vancomycin, prophylaxis should be considered for 1.6%, 3.9%, and 7.4%, respectively, fluoroquinolones, metronidazole, patients at high risk of infection, infor patients undergoing open chole- and amoxicillin–clavulanate, and cluding those undergoing open cho- cystectomy. Significantly lower rates 1467 controls receiving placebo or no lecystectomy, as described above, or of SSIs and postoperative pneumo- treatment. No significant difference who are considered to be at high risk nia were noted in patients receiving was found in the rates of infectious for conversion to an open procedure. antimicrobials compared with those complications (2.07% in patients Choice of agent. The data do who did not receive prophylaxis receiving antimicrobial prophylaxis not indicate a significant difference (p < 0.05). SSI rates were significantly versus 2.45% in controls) or SSIs among first-, second-, and third- decreased in laparoscopic chole- (1.47% in patients receiving antimi- generation cephalosporins. First- cystectomy patients who received crobial prophylaxis versus 1.77% in generation,307,308,312,315,319,323,330,336,338,343,344 ceftriaxone (0.1%) or other anti- controls). The authors of the meta- second-generation,308,314,315,318,323, microbials (0.2%) compared with analysis concluded that antimicrobi- 327-329,331,332,335,344-352 and third-generation those who received no antimicrobial al prophylaxis was not necessary for 308,309,315-317,321,322,332,333,338,349,353,354 prophylaxis (1.6%). SSI rates were low-risk patients undergoing elective cephalosporins have been stud- significantly decreased in open cho- laparoscopic cholecystectomy. An ied more extensively than other lecystectomy patients who received additional meta-analysis of 9 ran- antimicrobials. Limited data are ceftriaxone (1.0%) or other anti- domized controlled trials (n = 1437) available for ampicillin with genta- microbials (2.6%) compared with also concluded that prophylactic micin,355 piperacillin,356 amoxicillin– those who received no antimicrobial antimicrobials do not prevent infec- clavulanate,305,338,351,354 ciprofloxa- prophylaxis (4.4%). The study au- tions in low-risk patients undergoing cin,320,333,352,357 and cephalosporins or thors concluded that antimicrobial laparoscopic cholecystectomy.342 penicillins alone or in combination prophylaxis should be administered A small, prospective, nonran- with metronidazole, gentamicin, to all patients undergoing cholecys- domized study compared the use of or both metronidazole and tectomy, regardless of approach. The cefotaxime 1 g i.v. during surgery gentamicin.308 study had several limitations, includ- with an additional two i.v. doses Several studies have compared ing lack of randomization, lack of given eight hours apart after surgery first-generation cephalosporins adequate controls, and lack of clear (n = 80) with no antimicrobial pro- with second- or third-generation definition of patient selection for the phylaxis (n = 86) in patients under- agents.315,336,338,344-347,353,358 With one antimicrobial regimens. The statisti- going elective laparoscopic cholecys- exception,347 there was no signifi- cal analysis was not clearly defined. tectomy with accidental or incidental cant difference in efficacy among The study appears to have compared gallbladder rupture and spillage of agents. Other studies found no only the use and lack of use of an- bile.317 Patients who had spillage of significant differences in efficacy be- timicrobials (with ceftriaxone and gallstone calculi or whose operations tween ampicillin and cefamandole,335 other antimicrobials combined for were converted to open operations ciprofloxacin and ceftriaxone,333 analysis) and did not specifically were excluded from the study. The amoxicillin–clavulanate and cefo- compare the laparoscopic and open rate of SSIs did not significantly taxime,354 amoxicillin–clavulanate approaches. differ between treatment groups and cefamandole,351 ceftriaxone and The findings of this study contrast (2.5% with antimicrobials versus ceftazidime,321 and oral and i.v. cip- with those of several other published 3.4% without antimicrobial prophy- rofloxacin and i.v. cefuroxime.352,357 studies. A meta-analysis of 15 ran- laxis). Based on results of multivari- One study found that i.v. ampicillin– domized controlled studies evaluated ate analysis, routine antimicrobial sulbactam was associated with sig- the need for antimicrobial prophy- prophylaxis was not recommended nificantly lower rates of infection laxis in elective laparoscopic chole- for these patients unless they were compared with cefuroxime306 and cystectomy for patients at low risk diabetic, were older than 60 years, or that patients treated with oral cef of infection.313 Low risk was defined had an ASA classification of≥ 3 or the tibuten had significantly lower infec- as not having any of the following: duration of the procedure exceeded tion rates than those who received acute cholecystitis, a history of acute 70 minutes. amoxicillin–clavulanate.338

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Duration. The effect of dura- tectomy who have an increased risk in 9–30% of patients with uncom- tion of prophylaxis on outcome has of infectious complications. Risk plicated appendicitis who do not been evaluated. A single dose of a factors include performance of emer- receive prophylactic antimicrobials, cephalosporin was compared with gency procedures, diabetes, antici- though some reports suggest lower multiple doses in several studies; pated procedure duration exceeding complication rates in children with no significant differences in efficacy 120 minutes, risk of intraoperative uncomplicated appendicitis.165,360-365 were found.327,329,330,348,349,353,359 The gallbladder rupture, age of >70 Mean SSI rates for appendectomy largest study compared one dose years, open cholecystectomy, risk of reported in the most recent NHSN of cefuroxime with three doses in conversion of laparoscopic to open report (2006–08) were 1.15% (60 of 1004 patients with risk factors for cholecystectomy, ASA classification 5211) for NHSN risk index catego- infection who were undergoing of ≥3, episode of biliary colic within ries 0 and 1 versus 3.47% (23 of 663) biliary tract surgery.327 There was 30 days before the procedure, rein- for NHSN risk index categories 2 and no significant difference in the rates tervention in less than a month for 3.165 Laparoscopic appendectomy has of minor or major SSIs between the noninfectious complications of prior been reported to produce lower rates single- and multiple-dose groups. In biliary operation, acute cholecystitis, of incisional (superficial and deep) the majority of studies, one dose of anticipated bile spillage, jaundice, SSIs than open appendectomy in an antimicrobial was administered at pregnancy, nonfunctioning gallblad- adults and children in multiple meta- induction of anesthesia,306,312,338,352,354 der, and immunosuppression. Be- analyses and several randomized within 30 minutes before incision,338 cause some of these risk factors can- clinical trials.292,310,366-371 However, the or 1315,316,320,321 or 2338 hours before not be determined before the surgical rate of organ/space SSIs (i.e., intra- incision. Additional doses were given intervention, it may be reasonable to abdominal abscesses) was signifi- as follows: one dose 12 hours after give a single dose of antimicrobial cantly increased with laparoscopic administration of the initial dose,352 prophylaxis to all patients undergo- appendectomy. two doses 12 and 24 hours after ing laparoscopic cholecystectomy. Organisms. The most common administration of the initial dose,338 (Strength of evidence for prophylaxis microorganisms isolated from SSIs two doses every 6338 or 8317,319 hours for high-risk patients = A.) after appendectomy are anaerobic after surgery, and one dose 24 hours and aerobic gram-negative enteric after surgery315 and five days after sur- Appendectomy procedures organisms. Bacteroides fragilis is the gery.352 In one study, a second dose of Background. Cases of appendici- most commonly cultured anaerobe, amoxicillin–clavulanate or cefotax tis can be described as complicated and E. coli is the most frequent aer- ime was administered for procedures or uncomplicated on the basis of the obe, indicating that the bowel flora lasting longer than 4 hours.354 pathology. Patients with uncompli- constitute a major source for patho- Recommendations. A single dose cated appendicitis have an acutely gens.59,372,373 Aerobic and anaerobic of cefazolin should be administered inflamed appendix. Complicated streptococci, Staphylococcus species, in patients undergoing open biliary appendicitis includes perforated or and Enterococcus species also have tract procedures (Table 2). (Strength gangrenous appendicitis, including been reported. P. aeruginosa has been of evidence for prophylaxis = A.) peritonitis or abscess formation. reported infrequently. Alternatives include ampicillin– Because complicated appendicitis Efficacy. Antibiotic prophylaxis is sulbactam and other cephalosporins is treated as a complicated intra- generally recognized as effective in (cefotetan, cefoxitin, and ceftriax- abdominal infection,303 it has not the prevention of postoperative SSIs one). Alternative regimens for pa- been addressed separately in these in patients undergoing appendecto- tients with b-lactam allergy include guidelines. All patients with a suspect- my when compared with placebo.374 clindamycin or vancomycin plus ed clinical diagnosis of appendicitis, Choice of agent. Randomized con- gentamicin, aztreonam, or a fluoro- even those with an uncomplicated trolled trials have failed to identify quinolone; or metronidazole plus case, should receive appropriate pre- an agent that is clearly superior to gentamicin or a fluoroquinolone. operative i.v. antimicrobials for SSI other agents in the prophylaxis of Antimicrobial prophylaxis is not prevention, which, due to the com- postappendectomy infectious com- necessary in low-risk patients un- mon microbiology encountered, re- plications. An appropriate choice for dergoing elective laparoscopic cho- quires similar antimicrobial choices SSI prophylaxis in uncomplicated lecystectomies. (Strength of evidence to those used to treat complicated appendicitis would be any single against prophylaxis for low-risk appendicitis. agent or combination of agents that patients = A.) Antimicrobial pro- Approximately 80% of patients provides adequate gram-negative phylaxis is recommended in patients with appendicitis have uncompli- and anaerobic coverage. The second- undergoing laparoscopic cholecys- cated disease.59 SSI has been reported generation cephalosporins with an-

220 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis aerobic activity and a first-generation Patients who received both cefazolin ward being beneficial, but the results cephalosporin plus metronidazole and metronidazole had a signifi- were not statistically significant.374 A are the recommended agents on the cantly lower infection rate compared retrospective chart review questioned basis of cost and tolerability. Given with the other groups.384 Consistent the routine need for antimicrobial the relatively equivalent efficacy be- with the antibacterial spectrum of the prophylaxis in children with simple tween agents, a cost-minimization agents, a prospective study of antimi- appendicitis, due to relatively low approach is reasonable; the choice of crobial prophylaxis for colorectal pro- infection rates in children not receiv- agents should be based on local drug cedures found that the combination ing prophylaxis.365 However, these acquisition costs and antimicrobial of metronidazole with aztreonam did and other study authors have sug- sensitivity patterns. not show adequate coverage of gram- gested antimicrobial prophylaxis may A wide range of antimicrobials positive organisms.385 The Common be considered due to the morbidity have been evaluated for prophy- Principles section of these guidelines associated with infectious complica- laxis in uncomplicated appendicitis. provides additional considerations tions (e.g., prolonged hospitalization, The most commonly used agents for weight-based dosing. readmission, reoperation) and due to were cephalosporins. In general, a Duration. In most of the studies of the inability to preoperatively identify second-generation cephalosporin second- or third-generation cephalo- appendicitis. with anaerobic activity (cefoxitin or sporins or metronidazole combina- As a single agent, metronidazole cefotetan) or third-generation ceph- tions, a single dose376-378,380,383 or two was no more effective than placebo alosporins with partial anaerobic or three doses364,379,382 were given. in two double-blind studies that in- activity (cefotaxime) were effective, Although direct comparisons were cluded children 10 years of age or with postoperative SSI rates of <5% not made, there was no discernible older360 and 15 years of age or older.363 in most studies.364,375-381 difference in postoperative SSI rates In a randomized study that included Piperacillin 2 g was comparable between single-dose and multidose pediatric patients, ceftizoxime and to cefoxitin 2 g in a well-controlled administration in most studies. A cefamandole were associated with study.381 Metronidazole used alone randomized trial specifically compar- significantly lower infection rates was less effective than cefotaxime, ing different durations of regimens and duration of hospitalization than with infection rates above 10%.376 found no statistical difference between placebo.391 Both cefoxitin and a com- However, when metronidazole was a single preoperative dose, three doses bination of gentamicin and metroni- combined with cefazolin, ampicil- (preoperative dose plus two additional dazole were associated with a lower lin,382 or gentamicin,378,383 the post- doses), or a five-day regimen.386 A large rate of postoperative infection in a operative SSI rates were 3–6%. cohort study found that single doses randomized study that included pedi- A double-blind, randomized, of metronidazole and gentamicin in atric patients younger than 16 years.378 controlled trial was conducted at patients undergoing open appendec- Second-generation cephalosporins two hospitals to evaluate the effect tomy were effective and sufficient in with anaerobic activity (cefoxitin of metronidazole, which is effec- decreasing the SSI rate.387 or cefotetan) and third-generation tive against most anaerobes, and Pediatric efficacy. In pediatric cephalosporins with anaerobic activ- cefazolin, which is effective against patients, as with adults, preoperative ity (cefotaxime) were effective, with many aerobic organisms, singly and determination of complicated versus postoperative infection rates of <5% in combination, on the rate of sepsis uncomplicated appendicitis is dif- in two studies that included pediatric after appendectomy.384 Patients were ficult. A comprehensive review is not patients younger than 12 years.364,378,379 randomized into one of four groups: provided here, but this topic has been A single dose of gentamicin with metronidazole and placebo, cefazo- addressed by SIS.388 clindamycin was found to be safe lin and placebo, metronidazole and Two pediatric studies demonstrat- and effective in children with simple cefazolin, or double placebo. Patients ed no difference in SSI rates between appendicitis.392 with generalized peritonitis were ex- placebo and several antimicrobials. Recommendations. For uncom- cluded for ethical reasons. Treatment The first study compared metroni- plicated appendicitis, the recom- was started before the procedure and dazole, penicillin plus tobramycin, mended regimen is a single dose of a continued every 8 hours for 24 hours. and piperacillin.389 The second study cephalosporin with anaerobic activ- All patients in the trial were followed compared single-dose metronidazole ity (cefoxitin or cefotetan) or a single for about two weeks after discharge and single-dose metronidazole plus dose of a first-generation cephalo- from the hospital, and their surgical cefuroxime.390 A meta-analysis in- sporin (cefazolin) plus metronida- sites were inspected. A total of 271 cluding both adult and pediatric stud- zole (Table 2). For b-lactam-allergic patients were assessed. Sepsis rates ies found that for pediatric patients, patients, alternative regimens include at the two hospitals were similar. antimicrobial prophylaxis trended to- (1) clindamycin plus gentamicin,

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 221 ASHP Report Antimicrobial prophylaxis aztreonam, or a fluoroquinolone and Antimicrobial prophylaxis is rec- B. fragilis, and Clostridium species in (2) metronidazole plus gentamicin or ommended for small bowel surgery, the upper abdominal surgery group.402 a fluoroquinolone (ciprofloxacin or based on inferring effectiveness Efficacy. Antibiotic prophylaxis levofloxacin). (Strength of evidence from other clean-contaminated is generally recognized as effective for prophylaxis = A.) procedures. No specific prospective in the prevention of postoperative randomized studies could be identi- SSIs in patients undergoing small Small intestine procedures fied that addressed antimicrobial bowel surgery when compared with Background. Small intestine pro- prophylaxis for small bowel surgery. placebo. However, there are no procedures, or small bowel surgery as Antimicrobial prophylaxis for small spective placebo-controlled trials to defined by NHSN, include incision bowel surgical procedures related definitively establish the efficacy of or resection of the small intes- to a diagnosis of complicated intra- prophylactic antimicrobials in this tine, including enterectomy with or abdominal infection is not addressed patient population. without intestinal anastomosis or separately in these guidelines, as an- Choice of agent. The antimicrobi- enterostomy, intestinal bypass, and timicrobial therapy for established als selected for prophylaxis must strictureoplasty; it does not include intraabdominal infection should be cover the expected pathogens for the small-to-large bowel anastomosis. initiated preoperatively. small intestine. The microbial ecol- The risk of SSI in small bowel Organisms. The most common ogy of the proximal small intestine surgery is variable. The Surgical microorganisms isolated from SSIs (i.e., jejunum) is similar to that of the Site Infection Surveillance Service after small bowel surgery are aerobic duodenum, whereas the microbial in England (data collected by 168 gram-negative enteric organisms. flora of the ileum are similar to those hospitals in 13 categories of surgical Among the species isolated from of the colon. In patients with small procedures between 1997 and 2002) patients with SSI after small intes- intestine obstruction, the microbial reported an SSI rate of 8.9% (94 of tine surgery are gram-negative ba- flora are similar to those of the colon. 1056).393 Mean SSI rates for small cilli of gastrointestinal enteric origin No randomized controlled trials bowel procedures reported in the (aerobic and anaerobic) and gram- have confirmed that one antimicro- most recent NHSN report (2006–08) positive species, such as strepto- bial agent is superior to other agents were 3.44% for NHSN risk index cat- cocci, staphylococci, and enterococci, for SSI prophylaxis in small bowel egory 0 versus 6.75% for NHSN risk which is consistent with similar stud- surgery. An appropriate antimicrobi- index categories 1, 2, and 3. A study ies.401 E. coli is the most frequently al choice for SSI prophylaxis in small of 1472 patients undergoing bowel identified aerobe, indicating that the bowel surgery is any single agent or surgery (small bowel and colon) at bowel flora constitute a major source combination of agents that provides 31 U.S. academic medical centers of pathogens. Aerobic and anaerobic adequate coverage for the small in- between September and December streptococci, Staphylococcus species, testinal microbes. In patients with 2002 found an SSI rate of 8.7% for all and Enterococcus species also have small bowel obstruction, additional wound categories. For patients with been reported. coverage of anaerobic bacteria is also clean-contaminated wounds, the SSI The microbiology of 2280 SSIs af- desirable. rate was 7.9%; for those with con- ter upper or lower abdominal surgery For small intestine procedures taminated or dirty-infected wounds, conducted from 1999 to 2006 was with no evidence of obstruction, the SSI rates were 12.0% and 20.4%, described in the Prevalence of Infec- a first-generation cephalosporin respectively.394 tions in Spanish Hospitals (EPINE) (cefazolin) is recommended. For In a study of 178 penetrating study.402 The most frequent microor- patients with small intestine obstruc- stomach and small bowel injuries, ganisms isolated were E. coli (28%), tion, a first-generation cephalosporin 94% of which were operated on Enterococcus species (15%), Strep- with metronidazole or a second- within six hours of presentation, tococcus species (8%), P. aeruginosa generation cephalosporin with SSIs occurred in nearly 20% of cases. (7%), and S. aureus (5%; resistant anaerobic activity (cefoxitin or When associated colon injuries were to methicillin, 2%). The microbiol- cefotetan) is the recommended agent. excluded, SSIs occurred in 16% of ogy of SSIs after upper abdominal The choice of agents should be based gastric injuries and 13% of small tract surgery did not show any sig- on local drug acquisition costs and bowel injuries. Although 74% of nificant differences compared with antimicrobial sensitivity patterns. The patients received antimicrobials, SSIs of the lower tract, though there Common Principles section of these the specific timing of antimicrobial were relatively more staphylococci, guidelines provides additional consid- administration was not provided.395 K. pneumoniae, Enterobacter species, erations for weight-based dosing. Other studies of small bowel injury Acinetobacter species, and Candida Duration. Preoperative dosing of confirm similar SSI rates.396-400 albicans isolates and fewer E. coli, antimicrobials for SSI prevention, with

222 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis additional intraoperative antimicro- A Cochrane meta-analysis of and a trend toward fewer infections bial dosing dependent on the duration 17 randomized trials (n = 7843; 11 requiring mesh removal.410 of the operation and no postoperative hernioplasty trials, 6 herniorrha- Organisms. The most common dosing, is recommended for patients phy trials) in elective open inguinal microorganisms isolated from SSIs undergoing small bowel surgery. hernia repair reported SSI rates of after herniorrhaphy and hernioplasty Pediatric efficacy. In pediatric 3.1% versus 4.5% in the antimicro- are aerobic gram-positive organisms. patients, as with adults, antimicrobial prophylaxis and control groups, Aerobic streptococci, Staphylococcus bial prophylaxis for SSI prevention in respectively (OR, 0.64; 95% CI, 0.50– species, and Enterococcus species are small bowel surgery is recommended. 0.82).404 The subgroup of patients common, and MRSA is commonly Recommendations. For small with herniorrhaphy had SSI rates of found in prosthetic mesh infections.411 bowel surgery without obstruction, 3.5% and 4.9% in the prophylaxis Efficacy. Antibiotic prophylaxis the recommended regimen is a first- and control groups, respectively (OR, is generally recognized as effective generation cephalosporin (cefazolin) 0.71; 95% CI, 0.51–1.00). The sub- when compared with placebo in the (Table 2). For small bowel surgery group of patients with hernioplasty prevention of postoperative SSIs in with intestinal obstruction, the rec- had SSI rates of 2.4% and 4.2% in patients undergoing herniorrhaphy ommended regimen is a cephalospo- the prophylaxis and control groups, and hernioplasty. rin with anaerobic activity (cefoxitin respectively (OR, 0.56; 95% CI, Choice of agent. Randomized con- or cefotetan) or the combination 0.38–0.81). trolled trials have failed to identify an of a first-generation cephalosporin A meta-analysis of nine random- agent that is clearly superior to other (cefazolin) plus metronidazole. For ized trials of open hernioplasty for agents for SSI prophylaxis in hernia b-lactam-allergic patients, alterna- inguinal hernia documented SSI rates repair. A first-generation cephalo- tive regimens include (1) clindamy- of 2.4% (39 of 1642) in the antimi- sporin is the recommended agent on cin plus gentamicin, aztreonam, crobial group and 4.2% (70 of 1676) the basis of cost and tolerability. The or a fluoroquinolone and (2) met- in the control group. Antibiotics Common Principles section of these ronidazole plus gentamicin or a showed a protective effect in prevent- guidelines provides additional con- fluoroquinolone (ciprofloxacin or ing SSI after mesh inguinal hernia siderations for weight-based dosing. levofloxacin). (Strength of evidence repair (OR, 0.61; 95% CI, 0.40–0.92). Duration. Based on the evidence for prophylaxis = C.) Antibiotic prophylaxis did reduce the to date, a single preoperative dose rate of SSI in hernia patients under- of antimicrobial is recommended Hernia repair procedures going mesh hernioplasty.405 in hernioplasty and herniorrhaphy, (hernioplasty and herniorrhaphy) Based on the results of these two with redosing as recommended in the Background. All patients who un- systematic reviews, preoperative Common Principles section of these dergo hernioplasty (prosthetic mesh antimicrobial prophylaxis for SSI guidelines (if the procedure duration repair of hernia) or herniorrhaphy prevention is recommended for both exceeds the recommended redosing (suture repair of hernia) should herniorrhaphy and hernioplasty. interval from the time of initiation receive appropriate preoperative i.v. Compared with open hernia repair, of the preoperative dose or if there is antimicrobials for SSI prevention. laparoscopic hernia repair has been prolonged or excessive bleeding). The risk of SSIs is higher in hernio- reported to produce lower rates of Recommendations. For hernioplasty compared with herniorrha- incisional (superficial and deep) SSIs plasty and herniorrhaphy, the rec- phy.403 There is a significant risk of in randomized clinical trials.406-408 In ommended regimen is a single dose requiring prosthetic mesh removal in a recent multicenter randomized trial of a first-generation cephalosporin hernioplasty patients who develop an of laparoscopic versus open ventral (cefazolin) (Table 2). For patients SSI, and determination of whether incisional hernia repair (n = 162), known to be colonized with MRSA, mesh placement will be required for SSI was significantly less common it is reasonable to add a single pre- hernia repair is not always possible in in the laparoscopic group than in operative dose of vancomycin to the the preoperative period. the open repair group (2.8% versus recommended agent. For b-lactam- Mean SSI rates for herniorrhaphy 21.9%; OR, 10.5; 95% CI, 2.3–48.2; allergic patients, alternative regimens reported in the most recent NHSN p = 0.003).409 A meta-analysis of eight include clindamycin and vancomycin. report (2006–08) were 0.74% (21 of randomized trials comparing laparo- (Strength of evidence for prophylaxis 2852) for NHSN risk index category scopic and open incisional or ventral = A.) 0, 2.42% (81 of 3348) for NHSN risk hernia repair with mesh revealed that index category 1, and 5.25% (67 of laparoscopic hernia repair was asso- Colorectal procedures 1277) for NHSN risk index catego- ciated with decreased SSI rates (rela- Background. SSIs have been re- ries 2 and 3.165 tive risk, 0.22; 95% CI, 0.09–0.54) ported to occur in approximately

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4–10% of patients undergoing colon Efficacy. Results from random- and was similarly effective as i.v. cef- procedures, 3–7% in small bowel ized controlled trials and a Cochrane triaxone plus i.v. metronidazole in procedures, and 3–27% in patients review of 182 studies of over 30,000 patients undergoing elective colorectal after rectal procedures, based on the patients support the routine use procedures.431 The addition of i.v. cef risk index.165 However, when patients of prophylactic antimicrobials in amandole to oral neomycin plus oral are followed carefully in clinical trials, all patients undergoing colorectal erythromycin did not improve effica- rates tend to be considerably higher procedures.426 cy.430 In one of these studies, oral neo- (17–26%).412 Other septic compli- Choice of agent. The agent cho- mycin and erythromycin were more cations, such as fecal fistula, intra- sen for antimicrobial prophylaxis in effective than i.v. cefoxitin for proce- abdominal abscesses, peritonitis, and colorectal procedures should have dures lasting longer than 4 hours.445 septicemia, are serious concerns but activity against the anaerobic and A randomized controlled study was are much less common.413 Infectious aerobic floras of the bowel. The stopped early due to the significantly complication rates range from 30% most appropriate regimen for anti- higher rate of infection in the oral neo- to 60% without antimicrobial pro- microbial prophylaxis for colorectal mycin and erythromycin group (41%) phylaxis59,414 and are <10% with ap- procedure (e.g., oral, i.v, oral–i.v. compared with the single-dose i.v. propriate antimicrobial prophylaxis. combination) and the optimal choice metronidazole and ceftriaxone group A pooled analysis of clinical trials of of antimicrobial agent have not been (9.6%) (p < 0.01).446 Similarly, a study antimicrobial prophylaxis in colon fully resolved. of oral metronidazole and kanamycin procedures demonstrated that anti- Oral regimens. The efficacy of oral compared with the same medica- microbial use significantly reduced prophylactic antimicrobial agents tions given intravenously found an mortality rates (11.2% for control has been established in studies only increased rate of postoperative sep- versus 4.5% for treatment) and SSI when used with mechanical bowel sis (36% versus 6.5%, respectively) rates.415 preparation (MBP). A variety of (p < 0.001), greater numbers of E. coli The type and duration of the oral agents administered after MBP resistant to kanamycin, more bacte- procedure can affect the risk of have been evaluated for prophylaxis rial overgrowth, and antimicrobial- infection. Rectal resection is associ- for colorectal procedures. The most associated pseudomembranous colitis ated with a higher risk of infection common combinations include an in the oral group.447 However, the oral than is intraperitoneal colon resec- aminoglycoside (neomycin and, less antimicrobials were not given on a tion.416-418 Other risk factors include often, kanamycin, which is only avail- schedule expected to be effective, as extended procedure duration (e.g., able in injectable form in the United they were discontinued 36 hours be- >3.5 hours),59,412,418,419 impaired host States) plus a medication with an- fore the procedure. The fact that oral defenses,418 age of >60 years,418 hy- aerobic activity, usually erythromy- antibiotics were given for three days poalbuminemia,419,420 bacterial or cin427-434 or metronidazole.432,433,435-439 rather than less than one day, as is the fecal contamination of the surgical In placebo-controlled studies, the oral current practice, was suggested as a site,418,420 inadvertent perforation or combination was significantly more possible reason for the resistance and spillage,412,421 corticosteroid therapy,419 effective than placebo in reducing colitis observed. perioperative transfusion of packed SSIs.427,433,434,439,440 Postoperative SSI I.V. regimens. A wide range of i.v. red blood cells,394,418 hypothermia,422 rates were 0–11% with neomycin antimicrobials have been evaluated hyperglycemia,423,424 and obesity.412,418 plus erythromycin427-432 and 2–13% for prophylaxis in colorectal proce- Organisms. The infecting organ- with neomycin and metronida- dures. Cephalosporins are the most isms in colorectal procedures are zole.436-438 Combinations of neomy- common agents, usually adminis- derived from the bowel lumen, where cin and tetracycline,440 neomycin and tered as a single agent. The major- there are high concentrations of or- clindamycin,436 and neomycin and ity of studies found that single-agent ganisms. B. fragilis and other obligate tinidazole441 have also been used suc- first-generation cephalosporins anaerobes are the most frequently cessfully, with postoperative SSI rates (cefazolin and cephalothin)445,448-451 isolated organisms from the bowel, of <10%. The use of metronidazole were ineffective, with postopera- with concentrations 1,000–10,000 as a single agent appears to be less tive SSI rates ranging from 12% times higher than those of aerobes.425 effective, with reported SSI rates of to 39%.448,449 The lack of efficacy is E. coli is the most common aerobe. 12–15%.442-444 likely due to their lack of B. fragilis B. fragilis and E. coli comprise ap- Oral antimicrobials have been com- activity. The combination of cef proximately 20–30% of the fecal pared with i.v. agents in a few studies. azolin and metronidazole provides mass. They are the most frequently Oral neomycin plus oral erythromycin adequate coverage of pathogens and isolated pathogens from infected was similarly effective as i.v. cefoxitin in may be a cost-effective prophylaxis surgical sites after colon procedures. one study429 but inferior in another445 strategy.6,41

224 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

Second-generation cephalospo- hours for 24 hours postoperatively.16 rash), gastrointestinal events, and rins with anaerobic activity, such as All patients underwent MBP before C. difficile infection were seen in the cefoxitin and cefotetan, have been surgery. Patients with a serum cre- ertapenem group. The study authors widely evaluated. In single-agent atinine concentration exceeding 1.7 concluded that ertapenem is an ac- therapy, SSI rates ranged from 0% to mg/L were excluded from the study. ceptable alternative to cefotetan and 17%91,417,445,452-459; however, more than No statistically significant differences cefoxitin. Routine use of ertapenem half of the studies found SSI rates of were seen in deep and superficial for surgical prophylaxis remains >10%. incisional SSI rates between groups. controversial due to theoretical con- Third-generation agents, cefo- Significantly fewer superficial SSIs cerns regarding increases in resistant taxime and ceftriaxone, have been were seen in the single-dose group organisms and a potential increase in evaluated in a few trials; post- compared with the multidose group adverse events.477 operative SSI rates were 8–19% in procedures lasting longer than 3.5 Alternative agents for patients with single-agent use.456,460,461 In hours (22.2% versus 55%, p = 0.021). with a high likelihood of past se- some studies, second- or third- A pharmacodynamic study of these rious adverse event or allergy to generation cephalosporins were patients found the gentamicin con- b-lactams include (1) clindamycin combined with other i.v. agents, most centration at the time of surgical-site plus an aminoglycoside, aztreonam, commonly metronidazole.452,459-462 closure as the strongest independent or a fluoroquinolone and (2) metro- However, in all but one of these factor for infection.17 Of note, the nidazole plus an aminoglycoside or studies, a combination of a second- infection rate was 80% in 10 patients a fluoroquinolone.41 or third-generation cephalosporin with gentamicin concentrations of Combination oral and i.v. regi- plus metronidazole was no more <0.5 mg/L. mens. Combinations of oral and i.v. effective than the cephalosporin Other i.v. agents that have been antimicrobials have been used in an alone. The use of third- or fourth- evaluated either alone or in combina- attempt to further reduce postop- generation cephalosporins for rou- tion include aminoglycosides,464,466-469 erative infection rates. Regimens tine antimicrobial prophylaxis is clindamycin,466 ampicillin,467,469-471 include oral neomycin and eryth- not recommended as use may lead penicillins plus b-lactamase inhibi- romycin plus i.v. administration of to development of resistant organ- tors,464,465,468,472,473 doxycycline,470,474-476 a cephalosporin,416,417,429,445,449,478,479 isms.6,41,444,463 However, in institu- piperacillin,91,473 imipenem,462 and metronidazole,480,481 and gentamicin tions where there is increasing gram- ciprofloxacin.300 plus clindamycin.466 Postoperative negative resistance from isolates to Ertapenem, a broad-spectrum SSI rates in these studies ranged from first- and second-generation cepha- carbapenem, is approved by FDA for 0% to 7%. With one exception,416 losporins, a single dose of ceftriaxone the prophylaxis of SSIs after elective there was no significant difference plus metronidazole may be preferred colorectal procedures.67 Cefotetan between oral neomycin–erythro- over routine use of carbapenems. is also FDA approved for surgical mycin plus an i.v. antimicrobial Three small studies, with un- prophylaxis in clean-contaminated and oral neomycin–erythromycin der 200 patients each, found procedures (e.g., gastrointestinal alone.429,449,466,478 When combination i.v. ampicillin–sulbactam or procedures) in adult patients un- oral and i.v. agents were compared amoxicillin–clavulanate to be as dergoing elective colon or rectal with i.v. agents alone, combination effective as i.v. combinations of procedures.62 A large, multicenter, therapy was favored in five of six gentamicin and metronidazole,464 randomized controlled study com- studies417,429,445,449,480,482; the difference gentamicin and clindamycin,465 and pared a single 1-g i.v. dose of erta was significant in three.417,449,482 The cefotaxime and metronidazole for penem with cefotetan 2 g i.v. infused most recent Cochrane review found preventing SSIs in elective colorectal within 60 minutes before surgical that the infection rate was signifi- procedures. incision.412 All patients received MBP cantly lower with the combination A randomized controlled study preoperatively. SSI rates were signifi- of oral plus i.v. prophylaxis when of adult patients undergoing elective cantly lower in the ertapenem group compared with i.v. alone (relative colon or rectal procedures evalu- versus cefotetan in the per-protocol risk, 0.55; p = 0.000084) or with ated the use of a single high dose of (18.1% and 31.1%, respectively) and oral prophylaxis alone (relative risk, gentamicin 4.5 mg/kg i.v. plus met- the modified intent-to-treat (17.1% 0.34; p = 0.024).426 A recent report ronidazole 500 mg i.v. in sequential and 50.9%) populations. Ertapenem of over 2000 patients recorded pro- order over 30 minutes compared was found to be superior to cefotetan spectively in the Michigan Surgical with multiple standard doses of gen- for SSI prevention. Although not sta- Quality Collaborative—Colectomy tamicin 1.5 mg/kg plus metronida- tistically significant, higher rates of Best Practices Project and analyzed zole given preoperatively and every 8 skin-related events (i.e., pruritis and retrospectively revealed a signifi-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 225 ASHP Report Antimicrobial prophylaxis cantly lower rate of postoperative between groups for rates of abdomi- single-dose cefazolin, single-dose infections when 370 colectomy nal pain, SSIs, or intraabdominal cefotetan, and cefazolin given as one patients received MBP and oral an- abscesses. An increased number of preoperative dose and a second dose timicrobial prophylaxis compared gastrointestinal adverse events was three hours later for procedures with with propensity-matched patients also reported in another comparative a duration of less than three hours.118 receiving i.v. prophylaxis alone.483 study in the combination oral and SSI rates were significantly higher A multicenter, randomized, con- i.v. group (2.9%) compared with the with a single dose of cefazolin for trolled study of 491 patients who i.v.-only group (2.1%), although the procedures with a duration of greater received MBP plus oral antimicrobi- results were not statistically signifi- than three hours. Using an agent with als (kanamycin and erythromycin) cant.484 Overall, the evidence suggests a longer half-life can decrease the with i.v. cefmetazole (not available that the combination of oral antimi- necessity to redose the antimicrobial in the United States but noted by the crobials with MBP in addition to i.v. during long procedures. expert panel to have a similar spec- prophylactic antimicrobials reduces Pediatric efficacy. No well- trum of activity as cefotetan) or i.v. the rate of postoperative infections controlled studies have evaluated cefmetazole alone found no differ- compared with i.v. antimicrobials the efficacy of antimicrobial prophy- ence in SSI between groups for colon alone without MBP, although the laxis in pediatric patients undergo- procedures.484 However, the combi- addition of oral antimicrobials in- ing colorectal procedures. However, nation of oral and i.v. antimicrobials creases gastrointestinal symptoms. there is no reason to suspect that was significantly better than i.v. alone Duration. Single and multiple prophylaxis efficacy would be differ- for rectal procedures, particularly doses were compared in several stud- ent. The safety, efficacy, tolerability, abdominoperineal excision. Another ies.454-456,461,471,475 However, only two of and cost-effectiveness of intestinal study found the postoperative SSI these studies compared single doses lavage have been demonstrated in rates after rectal resection were 23% with multiple doses of the same two studies of 20 and 21 pediatric and 11%, respectively, for patients re- antimicrobial.471,475 There was no sig- patients.488,489 ceiving i.v. cefoxitin and cefoxitin plus nificant difference in infection rates Recommendations. A single dose oral neomycin and erythromycin. 417 between single-dose and multidose of second-generation cephalosporin The safety and tolerability of oral administration. One study found a with both aerobic and anaerobic antimicrobials have been investigated single dose of cefotaxime plus met- activities (cefoxitin or cefotetan) in two studies. One case–control ronidazole was significantly more ef- or cefazolin plus metronidazole is study found an increased incidence fective than three doses of cefotaxime recommended for colon procedures of C. difficile colitis among patients alone.461 The most recent Cochrane (Table 2). In institutions where there with oral plus i.v. antimicrobi- review found no benefit to extend- is increasing resistance to first- and als and MBP compared with i.v. ing the duration of prophylaxis second-generation cephalosporins antimicrobials and MBP alone.485 (p = 0.58).426 Generally, antimicrobial among gram-negative isolates from However, another case–control study prophylaxis should be continued for SSIs, the expert panel recommends found a lower rate (not statistically no more than 24 hours and can typi- a single dose of ceftriaxone plus significant) of C. difficile infection cally be stopped when the procedure metronidazole over routine use of in patients who had received oral is completed and the surgical site is carbapenems. An alternative regi- antimicrobials compared with those closed.6,41,444 No evidence supports men is ampicillin–sulbactam. In most who had not (1.6% versus 2.9%, greater efficacy for doses given after patients, MBP combined with a com- p = 0.09).486 A randomized controlled the completion of the procedure. bination of oral neomycin sulfate study of 300 patients undergoing Additional discussion on this topic plus oral erythromycin base or oral elective colorectal procedures found is found in the Common Principles neomycin sulfate plus oral metroni- significantly higher rates of nausea section of these guidelines. dazole should be given in addition and vomiting among patients receiv- Consideration should be given to i.v. prophylaxis. The oral antimi- ing three doses of oral antimicrobials to an additional dose of the i.v. an- crobial should be given as three doses (neomycin and metronidazole, 44% timicrobial if an agent with a short over approximately 10 hours the and 31%, respectively) in combina- half-life is used and the procedure afternoon and evening before the option with i.v. cefoxitin and MBP duration exceeds the recommended eration and after the MBP. Alternative compared with regimens including redosing interval (starting from the regimens for patients with b-lactam one dose of oral antimicrobials (18% time of initiation of the preoperative allergies include (1) clindamycin plus and 11%, respectively) and no oral dose) and if intraoperative blood loss an aminoglycoside, aztreonam, or a antimicrobials (13% and 9%, respec- occurs.6,41,120,418,444,445 No significant fluoroquinolone and (2) metroni- tively).487 No difference was noted difference was seen in SSI rates with dazole plus an aminoglycoside or a

226 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis fluoroquinolone. Metronidazole plus postoperative SSI rates.496,497,501-504,508 undergoing adenoidectomy, tonsil- aztreonam is not recommended as an In patients with cancer, preoperative lectomy,522,523 and septoplasty,524 alternative because this combination radiation and chemotherapy as well and systematic reviews have not has no aerobic gram-positive activ- as the stage of the malignancy may recommended prophylaxis for these ity.385 (Strength of evidence for pro- also affect infection risk.497,498,502-504 procedures.7,525,526 phylaxis = A.) Procedure-related risk factors for The efficacy of antimicrobial pro- infection include radical or bilateral phylaxis is best established for head Head and neck procedures neck dissections501,508 and reconstruc- and neck cancer surgery. Several Background. Elective procedures tion with myocutaneous flaps or small randomized, controlled trials of the head and neck are predomi- microvascular-free flaps.497-499,508 found high infection rates in placebo nantly clean or clean-contaminated.490 Organisms. The normal floras of groups (24–78%) and markedly low- Clean procedures include thyroid- the mouth and the oropharynx are er infection rates in the prophylaxis ectomy and lymph node excisions. responsible for most infections that groups (5.8–38%) using a variety Clean-contaminated procedures in- follow clean-contaminated head and of regimens, including cefazolin, clude all procedures involving an neck procedures.6,8,496,498,499,506,509-519 An- third-generation cephalosporins, incision through the oral or pharyn- aerobic and aerobic bacteria are abun- and ampicillin plus cloxacillin. Al- geal mucosa, ranging from paroti- dant in the oropharynx. As a result, though these studies were small, the dectomy, submandibular gland exci- postoperative SSIs are usually polymi- results are concordant, and the high sion, tonsillectomy, adenoidectomy, crobial and involve both aerobic and infection rates allowed the studies to and rhinoplasty to complicated anaerobic bacteria. The predominant reach statistical significance despite tumor-debulking and mandibular oropharyngeal organisms include the small sample sizes. Similar results fracture repair procedures requiring various streptococci (aerobic and an- were reported in several additional reconstruction. The frequency of aerobic species), other oral anaerobes small, uncontrolled studies.500,527-529 SSIs reported for clean procedures including Bacteroides species (but not Choice of agent. Several random- without antimicrobial prophylaxis is B. fragilis), Peptostreptococcus species, ized, single-center studies have com- <1%.491,492 In contrast, infection rates Prevotella species, Fusobacterium spe- pared antimicrobial regimens for in patients undergoing complicated cies, Veillonella species, Enterobacte- clean-contaminated procedures. head and neck cancer surgery are riaceae, and staphylococci. Nasal flora In one study, 189 patients quite high, with infection occurring includes Staphylococcus species and undergoing head and neck cancer in 24–87% of patients without an- Streptococcus species. procedures were randomized to timicrobial prophylaxis.493-497 While Efficacy. Clean procedures. Sys- receive cefazolin 1 g (n = 92) or many of these head and neck cancer temic administration of prophylactic amoxicillin–clavulanate (n = 97), procedures are clean-contaminated, antimicrobials has not been proven both given within one hour of inci- these procedures can fall into differ- effective in reducing SSI rates in pa- sion and every eight hours post- ent wound classifications. Head and tients undergoing clean procedures operatively for three doses.511 The neck cancer patients often have many of the head and neck and are not postoperative SSI rates were 24% of the risk factors for infection men- recommended for routine use.6-8,497,520 with cefazolin and 21% with tioned below.498 One randomized, double-blind, mul- amoxicillin–clavulanate; there was Postoperative SSI rates are af- ticenter study of 500 patients under- no statistically significant difference fected by age, nutritional status, and going thyroid procedures for goiter in infection rates in this under- the presence of concomitant medical or carcinoma found no difference powered study. Two studies have conditions such as diabetes mellitus, in postoperative SSI rates in those compared ampicillin–sulbactam to anemia, and peripheral vascular who received antimicrobial prophy- clindamycin and yielded discordant disease.496,499-504 Use of tobacco,498,505 laxis (0.8%) and those who did not results. One study of 242 patients alcohol,505,506 or drugs of abuse507 has (0.4%).491 (169 evaluable) undergoing head and also been associated with a higher Clean-contaminated procedures. neck cancer procedures compared risk of postoperative infection, par- Based on the best available evidence, ampicillin–sulbactam 1.5 g (n = 119) ticularly in patients with mandibular current guidelines and review articles and clindamycin 600 mg (n = 123) fracture. The hospital course, includ- recommend the use of antimicrobial given within one to two hours of ing length of hospitalization before prophylaxis for the majority of clean- incision and every six hours postop- operation, duration of antimicrobial contaminated procedures.6-8,497,520,521 eratively for a total of four doses.510 use before operation, length of op- However, antimicrobial prophylaxis No difference in SSIs was found, with eration, presence of implants, and did not lower infection risk in ran- 15 infections reported in each group previous tracheotomy can also affect domized controlled trials of patients (13% for the ampicillin–sulbactam

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 227 ASHP Report Antimicrobial prophylaxis group and 12% for the clindamycin allergies is clindamycin. (Strength of or additional neurosurgical proce- group). There was no significant dif- evidence against prophylaxis without dures,538,541-543 concurrent (remote, ference in adverse events between prosthesis placement = B; strength of incision, or shunt) or previous shunt groups. There was a higher rate of evidence for prophylaxis with pros- infection,536,539,545,546 and emergency C. difficile-positive patients in the thesis placement = C.) procedures.542,545 clindamycin group (n = 7) than in the Clean-contaminated procedures. Organisms. Data from most ampicillin–sulbactam group (n = 1), Antimicrobial prophylaxis has not published clinical trials indicate with no reported statistical analysis. been shown to benefit patients un- that SSIs are primarily associat- Another study of 212 patients undergoing tonsillectomy or functional ed with gram-positive bacteria, dergoing clean-contaminated head endoscopic sinus procedures. The S. aureus, and coagulase-negative and neck oncology surgery found preferred regimens for patients un- staphylococci.6,8,537-545,547-554 Sev- significantly fewer infections in the dergoing other clean-contaminated eral cohort studies revealed high ampicillin–sulbactam group (13.3%) head and neck procedures are (1) cef rates (up to 75–80% of isolates) of compared with the clindamycin azolin or cefuroxime plus metroni- MRSA540-543,548-552 and coagulase- group (27.1%) (p = 0.02).530 A greater dazole and (2) ampicillin–sulbactam. negative staphylococci among pa- number of gram-negative pathogens Clindamycin is a reasonable alterna- tients undergoing a variety of neuro- were recovered from patients ran- tive in patients with a documented surgical procedures.539,540,543,549 Other domized to the clindamycin group. b-lactam allergy. The addition of an skin organisms such as P. acnes The combination of gentamicin and aminoglycoside to clindamycin may may be seen after CSF shunt place- clindamycin was superior to cefazolin be appropriate when there is an in- ment, craniotomy, and other proce- in one older clinical trial.531 creased likelihood of gram-negative dures.536,555,556 Gram-negative bacteria Duration. Studies of clean- contamination of the surgical site. have also been isolated as the sole contaminated head and neck proce- (Strength of evidence for prophy- cause of postoperative neurosurgical dures found no difference in efficacy laxis in cancer surgery patients = A; SSIs in approximately 5–8% of cases between regimens of 24 hours and strength of evidence for prophylaxis and have been isolated in polymicro- longer regimens of three, five, or seven for other clean-contaminated pro- bial infections.537-539,541-545,547-550,552,553 days.499-501,505,507,512,524,531-534 Limited data cedures except tonsillectomy and Efficacy. Clean procedures. An- exist on single-dose prophylaxis in functional endoscopic sinus proce- timicrobial prophylaxis is recom- these procedures. dures = B.) mended for adult and pediatric One study of patients undergo- patients undergoing craniotomy ing free-flap reconstruction after Neurosurgery procedures and spinal procedures.7,520 One meta- head and neck procedures found a Background. Nosocomial central analysis of six studies found de- significantly lower rate of acquisition nervous system (CNS) infections do creased odds of meningitis in pa- and infection with MRSA in patients not often occur but have potentially tients undergoing craniotomy who receiving short-term cefuroxime and serious consequences and poor out- received antimicrobial prophylaxis metronidazole (one dose during in- comes, including death.536 One of (1.1%) versus no prophylaxis (2.7%) duction of anesthesia and one dose the greatest risks for these infections (p = 0.03).557 Two cohort studies540,543 eight hours postoperatively) com- in children and adults is undergoing in patients undergoing craniotomy pared with long-term therapy (same a neurosurgical procedure. A clas- at the same institution found that antimicrobials with additional doses sification system for neurosurgery, antimicrobial prophylaxis with clox- every eight hours for up to five days) validated by Narotam et al.,537 divides acillin or amoxicillin–clavulanate, (p = 0.005 and p = 0.01, respectively, procedures into five categories: clean, clindamycin for b-lactam-allergic for acquisition and infection).535 clean with foreign body, clean- patients, and other antimicrobials Recommendations. Clean proce- contaminated, contaminated, and (not detailed) had a significantly dures. Antimicrobial prophylaxis is dirty. Risk factors for postoperative lower infection rate (5.8%) than no not required in patients undergoing infections after neurological proce- prophylaxis (9.7%) (p < 0.0001).543 clean surgical procedures of the head dures include an ASA classification A significantly lower infection rate and neck. If there is placement of of ≥2,538 postoperative monitoring of of 4.6% was seen in low-risk patients prosthetic material, a preoperative intracranial pressure538,539 or ventric- (clean craniotomy, no implant) with dose of cefazolin or cefuroxime is ular drains536,538 for five or more days, antimicrobial prophylaxis compared reasonable, though there are few data cerebrospinal fluid (CSF) leak,539-541 with those without prophylaxis supporting the efficacy of prophylaxis procedure duration of more than (4.6% versus 10%, p < 0.0001). A in this setting (Table 2). A reasonable two to four hours,540,542-544 diabetes,544 significantly lower rate of scalp infec- alternative for patients with b-lactam placement of foreign body,536 repeat tions, bone flap osteitis, and abscess

228 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis or empyema was seen with antimi- dergoing neurosurgery is generally monitors.134 An international survey crobial prophylaxis compared with recommened.6,7,520,540,543,547,548,557,563 of neurosurgeons and critical care no prophylaxis. Antimicrobial pro- Efficacy for CSF-shunting pro- medicine and infectious diseases phylaxis demonstrated no difference cedures. Antimicrobial prophylaxis specialists illustrates the difference in postoperative meningitis540,543 and is recommended for adults under- in practices. The majority of neuro- infection rates in high-risk patients going placement of a CSF shunt.7 surgeons used or recommended the (those undergoing emergency, clean- Prophylaxis in patients undergoing use of antimicrobial prophylaxis with contaminated, and dirty procedures ventriculostomy or intraventrical EVDs (73.5%) and other monitoring or reoperation or with operative prophylaxis at the time of ventriculo- devices (59%), compared with rates times exceeding four hours).543 peritoneal shunt insertion has shown of 46–59% for critical care medicine Prospective studies involving large some benefit in reducing infection specialists and 35% for infectious numbers of patients have also dem- but remains controversial due to lim- diseases specialists. The majority of onstrated lower neurosurgical post- ited evidence.6,7 specialists did not recommend or use operative infection rates when anti- Because CNS infections after antimicrobial-coated EVD catheters. microbial prophylaxis is used.558-561 shunting procedures are responsible Two randomized controlled One such study of patients undergo- for substantial mortality and morbid- studies comparing antimicrobial- ing craniotomy, spinal, or shunting ity, especially in children, the possible impregnated shunts to standard, procedures was stopped early be- role of prophylactic antimicrobials non-antimicrobial-impregnated cause of an excessive number of SSIs in such procedures has been studied shunts along with antimicrobial in the placebo group.562 in numerous small, well-conducted, prophylaxis with i.v. cephalosporin Choice of agent. Studies of clean randomized controlled trials.564-571 found a decrease in rates of shunt in- neurosurgical procedures report- Meticulous surgical and aseptic tech- fections549 and a significant decrease ed antimicrobial regimens includ- niques and short procedure times were in CSF infection with antimicrobial- ing clindamycin,540,543,557 vancomy- determined to be important factors impregnated shunts.545 At this cin,542,557 cefotiam (not marketed in lowering infection rates after shunt time, routine use of antimicrobial- in the United States),557 piperacill placement. Although the number of impregnated devices is not recom- in,557 cloxacillin,540,543,557 oxacill patients studied in each trial was small, mended; additional well-designed in,542,557 cefuroxime,547 cefotaxime,548 two meta-analyses of these data dem- studies are needed to establish their sulfamethoxazole–trimethoprim,548 onstrated that antimicrobial prophy- place in therapy.7,578 cefazolin,542,544 penicillin G,542 and laxis use in CSF-shunting procedures Choice of agent. In CSF-shunting amoxicillin–clavulanate.540,542,543 A reduced the risk of infection by ap- procedures, no single antimicro- meta-analysis found no significant proximately 50%.572,573 bial agent has been demonstrated difference in the rates of postcra- Intrathecal pump placement in- to have greater efficacy than oth- niotomy meningitis with various volves the implantation of a perma- ers.546,548,551-554,579 There is a lack of antimicrobial regimens (single-dose nent intrathecal catheter to allow data on the necessity of antimicro- regimens of clindamycin, vancomy- instillation of medication. CNS bials with CNS penetration relating cin, or cefotiam; three doses of piper- infections may occur after these to prevention of infection in CNS acillin; four doses of cloxacillin; and procedures, which are performed in shunting procedures. six doses of oxacillin).557 both pediatric and adult populations. Duration. The majority of stud- A randomized, open-label, mul- Several retrospective series have re- ies support the use of single-dose ticenter study of 613 adult patients ported infection rates of 4.5–9% after prophylaxis regimens or regimens undergoing elective craniotomy, intrathecal baclofen pump place- with a duration of 24–48 hours shunt, or stereotactic procedures ment.574-576 There are minimal pub- postoperatively.6-8,520,539,546,549-552,579 found no difference in single doses lished trial data regarding appropri- There is a lack of data evaluating of cefotaxime and trimethoprim– ate prophylaxis for intrathecal pump the continuation of EVDs with and sulfamethoxazole in postoperative procedures. It has been suggested without antimicrobial prophylaxis. abscess formation, SSIs, and shunt that prophylaxis for intrathecal The international survey mentioned infections.548 pump procedures be managed simi- above asked respondents to indicate Duration. The majority of stud- larly to prophylaxis for CSF-shunting their recommended duration for an- ies included single doses of antimi- procedures.577 timicrobial prophylaxis with EVDs as crobials; therefore, the use of single- There is no consensus on the use either periprocedural, for 24 hours, dose antimicrobial prophylaxis of antimicrobial prophylaxis in pa- for the first three days, for the entire given within 60 minutes before tients with extraventricular drains time the device is in place, or other.135 surgical incision in patients un- (EVDs) or intracranial pressure The respondents from the specialties

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 229 ASHP Report Antimicrobial prophylaxis of neurosurgery, neurocritical care, failed to demonstrate that the use Endometritis has been reported and critical care had similar results, of perioperative sulfamethoxazole– to occur in up to 24% of patients in with 28–31% using or recommending trimethoprim reduced the frequency elective cesarean delivery and up to periprocedural antimicrobials, 4–10% of shunt infection.564 approximately 60% of patients un- for 24 hours, 2–4% for the first three Other studies have demonstrated dergoing nonelective or emergency days, 43–64% for the entire time the efficacy for prophylactic antimicrobi- section.584,585 Risk factors for endo- device is in place, and 0–14% for als.566,582 A single-center, randomized, metritis include cesarean delivery, other. The infectious diseases special- double-blind, placebo-controlled prolonged rupture of membranes, ists reported rates of 62%, 19%, 4%, trial of perioperative rifampin plus prolonged labor with multiple vagi- 12%, and 4%, respectively. trimethoprim was performed in pe- nal examinations, intrapartum fever, One retrospective single-center diatric patients.582 Among patients re- and low socioeconomic status.585,586 cohort study of 308 patients with ceiving rifampin plus trimethoprim, Patients with low socioeconomic EVDs placed for three days or more the infection rate was 12%, compared status may have received inadequate received antimicrobial prophylaxis with 19% in patients receiving pla- prenatal care. for the duration of EVD use (n = cebo. The study was ended because The factor most frequently asso- 209) compared with patients receiv- of the high infection rates before sig- ciated with infectious morbidity in ing cefuroxime 1.5 g i.v. every eight nificance could be achieved. Infection postcesarean delivery is prolonged hours for three doses or less fre- rates at the study institution had been labor in the presence of ruptured quently periprocedurally (timing not 7.5% in the years before the study. An membranes. Intact chorioamni- clearly defined in article) (n = 99).580 open-label randomized study, includ- otic membranes serve as a protective The overall rate of bacterial ventricu- ing pediatric patients, demonstrated a barrier against bacterial infection. litis was 3.9%, with 8 patients (3.8%) lower infection rate in a group receiv- Rupture of the membrane exposes in the extended-use group and 4 ing oxacillin (3.3%) than in a control the uterine surface to bacteria from patients (4%) in the short-term group (20%).566 the birth canal. The vaginal fluid prophylaxis group, the difference of Recommendations. A single dose with bacterial flora is drawn into which was not significant. The study of cefazolin is recommended for the uterus when it relaxes between authors concluded that there was no patients undergoing clean neuro- contractions during labor. Women benefit to the use of a prolonged du- surgical procedures, CSF-shunting undergoing labor for more than six ration of antimicrobial prophylaxis. procedures, or intrathecal pump to eight hours in the presence of Pediatric efficacy for CSF- placement (Table 2). Clindamycin ruptured membranes should be con- shunting procedures. Antimicro- or vancomycin should be reserved sidered at high risk for developing bial prophylaxis is recommended for as an alternative agent for patients endometritis.587 Other risk factors for children undergoing a CSF-shunting with a documented b-lactam allergy SSIs after cesarean delivery include procedure.7 The efficacy of antimi- (vancomycin for MRSA-colonized systemic illness, poor hygiene, obe- crobial prophylaxis is extrapolated patients). (Strength of evidence for sity, and anemia.587,588 from adult studies. prophylaxis = A.) Organisms. The normal flora of A retrospective pediatric study of the vagina include staphylococci, 384 CSF-shunting procedures found Cesarean delivery procedures streptococci, enterococci, lactoba- a lower infection rate in patients Background. Approximately 1.2 cilli, diphtheroids, E. coli, anaerobic who received antimicrobials (2.1%) million infants are born by cesarean streptococci (Peptococcus species compared with those who did not delivery in the United States annu- and Peptostreptococcus species), Bac- (5.6%), but this difference failed to ally.583 The infection rate after cesar- teroides species (e.g., Bacteroides reach statistical significance.581 Two ean delivery has been reported to be bivius, B. fragilis), and Fusobacte- randomized, prospective studies 4–15%,583 though recent NHSN data rium species.584,587,589-592 Endometritis that included pediatric patients did showed an infection rate of 2–4%.165 infections are often polymicrobial not demonstrate a significant dif- Postpartum infectious complica- and include aerobic streptococcus ference in infection rates between tions are common after cesarean (particularly group B b-hemolytic the control group and the groups delivery. Endometritis (infection of streptococcus and enterococci), that received cefotiam571 (not avail- the uterine lining) is usually identi- gram-negative aerobes (particularly able in the United States) or methi fied by fever, malaise, tachycardia, E. coli), gram-negative anaerobic cillin.568 A randomized, double-blind, abdominal pain, uterine tenderness, rods (particularly B. bivius), and placebo-controlled study that in- and sometimes abnormal or foul- anaerobic cocci (Peptococcus species cluded pediatric patients undergoing smelling lochia.584 Fever may also be and Peptostreptococcus species). Ure- ventriculoperitoneal shunt surgeries the only symptom of endometritis. aplasma urealyticum has been com-

230 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis monly isolated from endometrial of Pediatrics (AAP), based on their and AAP.584,607 See the Common and surgical-site cultures. Additional efficacy, narrow spectrum of activity, Principles section of these guidelines commonly isolated organisms from and low cost.584 This recommendation for additional discussion on antimi- SSIs include Staphylococcus species is supported by a meta-analysis of 51 crobial timing. and enterococci. randomized controlled trials com- A meta-analysis of three ran- Efficacy. While the use of anti- paring at least two antimicrobial reg- domized controlled trials and two microbial prophylaxis in low-risk imens that concluded that ampicillin nonrandomized controlled studies procedures (i.e., those with no active and first-generation cephalosporins provided evidence that preoperative labor and no rupture of membranes) have similar efficacy.600 antimicrobial administration signifi- has been brought into question Newer prospective randomized cantly decreased the rate of endome- by the results of several random- controlled and cohort studies have tritis compared with administration ized, placebo-controlled studies that evaluated the addition of met- after cord clamping (3.9% and 8.9%, found no reduction in infectious ronidazole, azithromycin,601-603 or respectively; p = 0.012).605 A lower complications (fever, SSI, urinary doxycycline601 to a first- or second- SSI rate was also seen with preop- tract infection, or endometritis) with generation cephalosporin to extend erative antimicrobial administration the use of prophylaxis, the majority the spectrum of activity against (3.2% versus 5.4%), though this of these evaluations were underpow- common organisms isolated from difference was not significant. The ered and included administration endometrial and surgical-site cul- overall rate of infection-related mor- of antimicrobial prophylaxis at cord tures, specifically U. urealyticum and bidity was also significantly lower. clamping.593-599 However, the ef- Mycoplasma species. These studies No differences between the groups ficacy of antimicrobial prophylaxis found significantly lower rates of were seen in neonatal outcomes, in- in cesarean delivery has been shown postoperative infections (including cluding sepsis, sepsis workups, and in several studies and two meta- endometritis and SSI) and a shorter neonatal intensive care unit admis- analyses for both elective and non- duration of hospital stay compared sions. The largest study included in elective procedures. Therefore, prophy- with prophylaxis with a first- or this meta-analysis was a prospective, laxis is recommended for all patients second-generation cephalosporin randomized, controlled, double- undergoing cesarean delivery.584,592 alone.601-604 Antibiotic administration blind, single-center, double-dummy One meta-analysis that reviewed occurred either postoperatively or study of 357 patients comparing 7 placebo-controlled randomized after cord clamping in these stud- cefazolin 1 g i.v. given preoperatively trials in low-risk elective cesarean ies. Further study, particularly with and after cord clamping, which had delivery found that prophylaxis was preoperative antimicrobial admin- results consistent with the overall associated with a significant decrease istration, is needed to confirm these meta-analysis.606 in endometritis and fever.592 A larger preliminary findings and establish a In a recent randomized trial of meta-analysis of 81 randomized tri- place in therapy for this practice. more than 1100 women undergoing als with 11,937 women undergoing Timing. Historically, administra- cesarean section between 2004 and both elective and nonelective cesar- tion of antimicrobials in cesarean 2010, Witt and colleagues608 found ean delivery found that antimicrobial delivery was delayed until after cord no difference in SSI rates for patients prophylaxis was associated with a clamping.600,605,606 The principal rea- having antimicrobial administration significant reduction in risk of fever, sons were to avoid suppression of before surgical incision compared endometritis, SSI, urinary tract in- the neonate’s normal bacterial flora with those who received antimicro- fection, and serious infection.585 The that could promote the selection of bial prophylaxis at the time of cord relative risk for endometritis in elec- resistant organisms and concern that clamping. All patients received a tive cesarean section was 0.38 (95% the antimicrobials could potentially single dose of cefazolin 2 g. CI, 0.22–0.64) in those receiving an- mask neonatal infection, complicat- Duration. A meta-analysis of 51 timicrobial prophylaxis compared to ing evaluation of neonatal sepsis. studies found that multidose regimens those receiving no prophylaxis. However, more contemporary data provided no apparent benefit over Choice of agent. Although several support the administration of anti- single-dose regimens.600 The use of different antimicrobials used alone microbial prophylaxis before surgical single-dose prophylaxis is supported or in combination for antimicrobial incision to protect against bacte- by ACOG and AAP for procedures prophylaxis during cesarean delivery rial contamination of the surgical lasting less than two hours.584 Ad- have been evaluated, the use of first- site and decrease the risk of infection. ditional intraoperative doses may be generation cephalosporins (specifi- The practice of antimicrobial pro- warranted for patients with excessive cally cefazolin) has been advocated by phylaxis administration before sur- blood loss or for whom the duration ACOG and the American Academy gical incision is endorsed by ACOG of the procedure is extended.

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For additional discussion of dos- nal approach in 32.1%. Of hyster- nancy, prior radiation therapy, and ing, see the Common Principles sec- ectomies performed via the vaginal the presence of indwelling drainage tion of these guidelines. approach, 32.4% also used laparos- catheters.619,620 Recommendation. The recom- copy.609 The ACOG Committee on Organisms. The vagina is nor- mended regimen for all women un- Gynecologic Practice recommends mally colonized with a wide variety dergoing cesarean delivery is a single vaginal hysterectomy as the approach of bacteria, including gram-positive dose of cefazolin administered before of choice for benign disease, based and gram-negative aerobes and anaer- surgical incision (Table 2). (Strength on evidence of better outcomes and obes. The normal flora of the vagina of evidence for prophylaxis = A.) For fewer complications.613 Laparoscopic includes staphylococci, streptococci, patients with b-lactam allergies, an abdominal hysterectomy is an al- enterococci, lactobacilli, diphthe- alternative regimen is clindamycin ternative when the vaginal route is roids, E. coli, anaerobic streptococci, plus gentamicin. not indicated or feasible.613,614 Of Bacteroides species, and Fusobac- note, ACOG has stated that the su- terium species.589,624 Postoperative Hysterectomy procedures pracervical approach—removal of vaginal flora differs from preopera- Background. Hysterectomy is sec- the uterus with preservation of the tive flora; the amount of enterococci, ond only to cesarean delivery as the cervix—should not be recommended gram-negative bacilli, and Bacteroides most frequently performed major as a superior technique for hysterec- species increases postoperatively. gynecological procedure in the United tomy due to the lack of advantage in Postoperative changes in flora may States, with over 600,000 hysterecto- postoperative complications, urinary occur independently of prophylactic mies performed annually.609 Uterine symptoms, or sexual function and antimicrobial administration and fibroid tumors account for 40% of the increased risk of future trachelec- are not by themselves predictive of all presurgical diagnoses leading tomy to remove the cervical stump.615 postoperative infection.589,625,626 Post- to hysterectomy.609 Other common Infections after hysterectomy operative infections associated with diagnoses are dysfunctional uterine include superficial and organ/space vaginal hysterectomy are frequently bleeding, genital prolapse, endome- (vaginal cuff infection, pelvic cellu- polymicrobial, with enterococci, triosis, chronic pelvic pain, pelvic litis, and pelvic abscess) SSIs.589 The aerobic gram-negative bacilli, and inflammatory disease, endometrial reported SSI rates between January Bacteroides species isolated most fre- hyperplasia, and cancer. 2006 and December 2008 in the quently. Postoperative SSIs after ab- Hysterectomy involves the re- United States, based on NNIS risk in- dominal and radical hysterectomies moval of the uterus and, occasion- dex category, were 0.73–1.16 per 100 are also polymicrobial; gram-positive ally, one or two fallopian tubes, the procedures for vaginal hysterectomy cocci and enteric gram-negative ba- ovaries, or a combination of ovaries and 1.10–4.05 per 100 procedures cilli predominate, and anaerobes are and fallopian tubes.610 Radical hyster- for abdominal hysterectomy.165 A frequently isolated.626,627 ectomy entails removal of the uterus, multicenter surveillance study found Efficacy. A meta-analysis of 25 fallopian tubes, and ovaries and ex- a mean infection rate of 2.53% asso- randomized controlled trials dem- tensive stripping of the pelvic lymph ciated with all types of hysterectomy onstrated the efficacy of antimicro- nodes in patients with extension and a significantly lower mean rate bial prophylaxis, including first- and of their cancer. Hysterectomies are of infection with laparoscopic versus second-generation cephalosporins performed by a vaginal or abdominal abdominal hysterectomies (1.15% and metronidazole, in the preven- approach using a laparoscopic- or versus 3.44%, respectively).325 tion of infections after abdominal robot-assisted method. During a Risk factors for infection after hysterectomy.628 The infection rates vaginal hysterectomy, the procedure vaginal or abdominal hysterectomy were 21.1% with placebo or no is completed through the vagina with include longer duration of surgery, prophylaxis and 9.0% with any an- no abdominal incision. Abdominal young age, diabetes, obesity, pe- timicrobial. Another meta-analysis hysterectomy involves an abdominal ripheral vascular disease, collagen found that the rate of postoperative incision. Laparoscopic and robotic disease, anemia, transfusion, poor infection (surgical and pelvic sites) methods involve small incisions nutritional status, and previous his- in women undergoing vaginal hys- and require additional equipment, tory of postsurgical infection.590,616-622 terectomy who received placebo or increased operator experience, and The depth of subcutaneous tissue is no prophylactic antimicrobial ranged increased length of procedures.611,612 also a significant risk factor for infec- from 14% to 57%, which was sig- In the United States, between 2000 tion after abdominal hysterectomy.623 nificantly higher than the 10% rate and 2004, the abdominal approach Additional risk factors for infection reported with antimicrobials.629 for hysterectomy was used in 67.9% after radical hysterectomy for cervical Malignant disease as the reason of surgical procedures and the vagi- cancer include the presence of malig- for hysterectomy is a common ex-

232 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis clusion from studies of antimicro- 1 g (6.3%).617 A multicenter, ran- ferent antimicrobial have shown bial prophylaxis. Older, prospective, domized, double-blind, active- and the two regimens to be equally placebo-controlled studies found a placebo-controlled study compared effective in reducing the postop- lower rate of SSIs with antimicrobial single doses of ampicillin, cefazolin, erative infection rate in women prophylaxis after radical hysterecto- and placebo administered to women undergoing vaginal and abdominal my.619,630-633 The applicability of these undergoing elective total abdominal hysterectomies.635-643,645-650,655-663 The results is limited by small sample size hysterectomy at two centers in Thai- limited comparative trials involving and the inclusion of antimicrobials land.653 The study found a signifi- single-dose cefazolin637,654,655,664 or not available in the United States. cantly lower rate of infection, includ- ampicillin–sulbactam654,663 indicate Radical hysterectomy is primar- ing superficial and deep SSIs, urinary that a single dose of antimicrobial ily completed through an abdominal tract infections, vaginal cuff infec- is sufficient prophylaxis for SSIs for approach but can also be performed tion, and pneumonia, with cefazolin vaginal hysterectomy. Single doses of by a vaginal approach and using (10.3%) compared with placebo cefotetan, ceftizoxime, or cefotaxime laparoscopic or robotic methods.634 (26.9%) and ampicillin (22.6%). No appear to be as effective as multiple Therefore, antimicrobial prophylaxis difference was seen between ampi- doses of cefoxitin.644-649,665 A second would be warranted, regardless of cillin and placebo. The study authors dose of antimicrobial is warranted approach. No placebo-controlled concluded that cefazolin was more when the procedure lasts three hours studies have been conducted to effective than ampicillin for elective or longer or if blood loss exceeds evaluate the efficacy of antimicrobial total abdominal hysterectomy. 1500 mL.9,654 prophylaxis when used for laparo- A randomized controlled study of Recommendation. The recom- scopic hysterectomy. 511 patients undergoing laparoscop- mended regimen for women under- Choice of agent. Cephalosporins ic gynecological procedures at one going vaginal or abdominal hysterec- are the most frequently used and center in Italy compared single doses tomy, using an open or laparoscopic studied antimicrobials for proof amoxicillin–clavulanate 2.2 g and approach, is a single dose of cefazolin phylaxis in vaginal and abdominal cefazolin 2 g i.v. administered 20–30 (Table 2). Cefoxitin, cefotetan, or hysterectomies. Studies directly minutes before the procedure.654 A ampicillin–sulbactam may also be comparing different cephalosporins second dose was given if the surgery used. Alternative agents for patients have found no significant differ- lasted over three hours or there was with a b-lactam allergy include (1) ences in rates of infection in vaginal extensive blood loss (>1500 mL). No either clindamycin or vancomycin hysterectomy and have indicated significant differences in the rates of plus an aminoglycoside, aztreonam, that first-generation cephalosporins any postoperative infection, includ- or a fluoroquinolone and (2) met- (primarily cefazolin) are equivalent ing SSIs, were found between groups. ronidazole plus an aminoglycoside to second- and third-generation The statistical power of the study was or a fluoroquinolone. (Strength of agents.635-644 In abdominal hysterec- not stated. evidence for prophylaxis = A.) tomy, no significant differences in In light of the organisms encoun- the rates of serious infections were tered in the vaginal canal and com- Ophthalmic procedures noted between second- and third- parative studies conducted among Background. Ophthalmic proce- generation cephalosporin reg- different classes of cephalosporins, dures include cataract extractions, imens.641,645-649 Few comparisons cefazolin, cefotetan, cefoxitin, cefu- vitrectomies, keratoplasties, intra- have been made between second- roxime, and ampicillin–sulbactam ocular lens implantation, glaucoma generation cephalosporins and ce- have been supported as appropriate procedures, strabotomies, retinal fazolin. Cefazolin has been at least first-line choices for prophylaxis detachment repair, laser in situ ker- as effective in preventing infectious during vaginal or abdominal hys- atomileusis, and laser-assisted sub- complications as second- and third- terectomy.6,9,41 Alternative agents for epithelial keratectomy. Most of the generation cephalosporins.636,650-652 patients with a history of immediate available data regarding antimicro- However, one double-blind con- hypersensitivity to penicillin include bial prophylaxis involve cataract trolled study of 511 women undergo- either clindamycin or metronidazole procedures. The goal of prophylaxis ing abdominal hysterectomy found plus an aminoglycoside or a fluoro- is primarily to reduce acute post- that the risk of major SSIs requiring quinolone (ciprofloxacin, levofloxa- operative endophthalmitis, defined antimicrobial therapy was signifi- cin, or moxifloxacin) or aztreonam as severe intraocular inflammation cantly higher in the group receiving (with clindamycin only). due to infection, which can lead to preoperative cefazolin 1 g (11.6%; Duration. Studies comparing loss of vision if untreated.666 Since relative risk, 1.84; 95% CI, 1.03–3.29) single doses of one antimicrobial 2000, the reported frequency of than in those treated with cefotetan with multidose regimens of a dif- endophthalmitis after ophthalmic

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 233 ASHP Report Antimicrobial prophylaxis procedures is low worldwide, ranging and inner canthus (corner of the eye) postoperative endophthalmitis from 0% to 0.63%.667-680 The reported preoperatively and postoperatively among patients undergoing cata- time from procedure to diagnosis of are used. Many of the available studies ract procedure with intracameral endophthalmitis ranges from one are flawed with retrospective or un- cefazolin added to the previous day to six weeks, with the majority controlled design, inadequate follow- routine prophylaxis of preoperative of infections identified within one up, variations in surgical techniques eyelid cleansing with soap for three week. 666,669,671,673,674,681-683 (including disinfection, antimicrobial days670 and povidone–iodine eye area Potential risk factors for post- prophylaxis strategies, and methods preparation,670,674 topical antimicro- operative ophthalmic infections for performing procedures), and lim- bial, and corticosteroid preparations include preoperative factors such as ited reporting of clinical outcomes. given at the end of the procedure and diabetes,666 active ocular infection The large, randomized, partially- postoperatively. One study found a or colonization,666,684 lacrimal drain- masked, placebo-controlled, mul- significant decrease and a relative risk age system infection or obstruction, tinational, multicenter study con- reduction of 88.7% in postoperative age of >85 years,685 and immuno- ducted by the European Society of endophthalmitis with intracameral deficiency.684 Procedure-related risk Cataract and Refractive Surgeons cefazolin.670 The other found a de- factors include clear corneal inci- (ESCRS) compared the rate of crease from 0.63% to 0.055% in post- sions (as opposed to scleral tunnel postoperative endophthalmitis in operative endophthalmitis with in- incisions),680,686 any surgical com- over 16,600 patients undergoing tracameral cefazolin.674 No statistical plication, vitreous loss,684 posterior routine cataract procedures at 24 analysis was performed in this study. capsule tear,681,684,685 silicone intra- centers in Europe randomized to one A retrospective cohort study of ocular lens implantation,677,680 and the of four perioperative prophylaxis patients undergoing cataract proce- nonuse of facemasks in the operating groups.679,680,694 Patients received no dure at one center in Canada between theater.681 antimicrobial prophylaxis, intra- 1994 and 1998 found no significant Organisms. Among organisms cameral cefuroxime at the end of difference in the rate of postopera- isolated from patients developing the procedure alone, perioperative tive endophthalmitis with preopera- postoperative endophthalmitis after levofloxacin 0.5% ophthalmic solu- tive topical antimicrobials compared cataract procedure, approximately tion given within the hour before with none.668 A significant decrease in 25–60% were coagulase-negative the procedure, or both intracameral endophthalmitis was seen with sub- Staphylococcus species, primarily cefuroxime and perioperative levo- conjunctival administration of anti- S. epidermidis.668,670,671,673,674,678,683,684,686 floxacin. All patients had the eye area microbials at the end of the procedure Other gram-positive organisms iden- disinfected with povidone–iodine compared with no antimicrobials. tified included S. aureus, Streptococcus 5% preoperatively and received topi- Several prospective studies have species, Enterococcus species, P. acnes, cal levofloxacin postoperatively. The shown decreases in ocular flora, mea- and Corynebacterium species. Gram- study was stopped after an interim sured by bacterial isolate and CFU negative organisms isolated included analysis due to results of a multivari- counts, with preoperative antimicro- Serratia species, Klebsiella species, ate analysis indicating that patients bial irrigation,675 topical antimicrobi- P. mirabilis, and P. aeruginosa. These not receiving intracameral cefurox- als,687,688,691,692,698-700 and intracameral organisms represent the normal flora ime were approximately five times antimicrobials.682 These studies did isolated preoperatively in a number more likely to develop endophthal- not report rates of endophthalmitis, of studies.675,687-693 mitis. The study has been questioned limiting the application of the results. Efficacy. Data on antimicrobial for its high rate of endophthalmitis, Choice of agent. Along with careful prophylaxis efficacy in ophthalmic selection of cefuroxime due to gaps site preparation and disinfection, the procedures to prevent endophthal- in gram-negative coverage, un- ideal antimicrobial prophylaxis agent mitis are limited; however, prophy- known drug concentrations in the should be bactericidal against com- laxis is common.684 The low rate aqueous humor, risks of hypersen- mon pathogens of postoperative en- of postoperative endophthalmitis sitivity, the lack of a commercially dophthalmitis and be used safely in makes it difficult to complete an available preparation, the lack of a the eye.6,8,684 There is no consensus on adequately powered study to show subconjunctival cefuroxime treat- the agent of choice for antimicrobial efficacy of antimicrobial prophylaxis ment group, selection of topical levo- prophylaxis in ophthalmic proce- in ophthalmic procedures; therefore, floxacin, and methods for statistical dures, and no agent is FDA-approved surrogate markers of eradication of analysis.695-697 for this indication. There are limited normal flora bacteria and reduction Two single-center, historical- studies evaluating the efficacy of a of bacterial count on the conjunctiva, controlled studies in hospitals in particular choice of antimicrobial lower and upper eyelids, eyelashes, Spain reported decreases in acute prophylaxis for ophthalmic surger-

234 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis ies. The most efficacious antimicro- bination with an antiseptic agent treatment groups. Although not bial cannot be determined from the (chlorhexidine)682 showed no sig- statistically significant, logistic re- available data due to study flaws and nificant difference in the reduction gression found that cultures from pa- a lack of direct comparisons. Lo- of culture results compared with an tients treated with tobramycin were cal ocular flora resistance patterns antiseptic alone (povidone–iodine two times more likely to be positive should be monitored to aid in the or chlorhexidine)682,690 and no anti- than those treated with ofloxacin. selection of appropriate agents for microbial prophylaxis. The study had low power and did not prophylaxis.683,689,701 A randomized controlled study compare baseline and posttreatment Based on the available literature, compared the antimicrobial activity culture results for any treatment use of povidone–iodine as a preop- and safety of trimethoprim 0.1%– group. erative antiseptic agent is recom- polymyxin B sulfate 10,000 units/mL Fluoroquinolones have been mended to decrease ocular microbes ophthalmic solution and tobramycin found in studies to significantly and thereby prevent endophthal- 0.3% ophthalmic solution in patients decrease the ocular culture results mitis.6,684,702 Povidone–iodine 5% or undergoing cataract procedures.692 from baseline667,673,691,698,700,706; achieve 10% is instilled in the conjunctival All patients received one drop and aqueous humor, vitreal, and corneal sac and applied topically to the ocu- a subconjunctival injection of cor- tissue concentrations adequate to lar skin surface.703 The most effective ticosteroids and gentamicin post- prevent and treat common ocular protocol has not been established, as operatively followed by one drop of pathogens705,707-710; and result in im- povidone–iodine is frequently used study medication four times daily proved ocular measurements (i.e., vi- in combination with other antimi- for five to seven days. No significant sual acuity, epithelial cell counts, and crobials.670,674,675,678,687,704 Chlorhexi- differences were seen between groups epithelial healing).711-716 A retrospec- dine has been used as an effective for positive culture results from con- tive multicenter case series of 20,013 alternative to povidone–iodine, par- junctiva at baseline, at procedure, patients who underwent uncompli- ticularly in patients who are iodine or at postoperative days 5–7 or in cated cataract surgeries and received allergic.682,703 lid margin culture at baseline and fourth-generation fluoroquinolones Ophthalmic surgeons surveyed postoperative days 5–7. A higher rate preoperatively and postoperatively in the United Kingdom reported of positive cultures at procedure was reported the rates of postoperative that commonly used antimicrobial seen in the trimethoprim–polymyxin endophthalmitis.673 Endophthalmitis prophylactic agents included cepha- group (37 of 59 cultures, 63%) com- occurred in 9 (0.06%) of 16,209 sur- losporins, aminoglycosides, vanco- pared with 13 (41%) of 32 cultures geries in patients treated with gati- mycin, chloramphenicol, neomycin in the tobramycin group (p = 0.043). floxacin 0.3% ophthalmic solution alone or in combination with poly- Both medications eradicated the (95% CI, 0.03–0.1%) and in 5 (0.1%) myxin, and fluoroquinolones.695,703 majority of bacteria on the day of of 3,804 surgeries in patients treated A similar survey of members of procedure and postoperative days with moxifloxacin 0.5% ophthalmic the American Society of Cataract 5–7. Aqueous humor concentra- solution (95% CI, 0.05–0.3%). There and Refractive Surgery found that tions did not achieve the MICs of were no significant differences in ef- over 90% of respondents used S. aureus or S. epidermidis and were ficacy between agents. fluoroquinolones (mainly fourth- undetectable for polymyxin B sulfate. In a retrospective cross-sectional generation agents), vancomycin, and The adverse events of irritation and study conducted over a 10-year period cephalosporins.697 These antimicro- allergic reaction were experienced by with third- and fourth-generation bials have been recommended in three patients in the trimethoprim– fluoroquinolones, significantly lower practice guidelines.6 polymyxin group. The study authors rates of endophthalmitis were re- Cephalosporins, specifically cef concluded that there was no dif- ported for the fourth-generation azolin, cefuroxime, and ceftazidime, ference between trimethoprim and agents moxifloxacin and gatifloxacin have been shown to be safe and ef- tobramycin in ocular flora reduction. (0.56 per 1000 cataract surgeries) fective in decreasing postoperative A randomized controlled study than for the third-generation agents endophthalmitis when added to compared conjunctiva and contact ciprofloxacin and ofloxacin (1.97 per regimens of povidone–iodine and lens culture results after treatment 1000 surgeries) (p = 0.0011).671 topical antimicrobials.670,674,677,679,680,699 with tobramycin 0.3% versus ofloxa- Route. There is no consensus Vancomycin has been shown to de- cin 0.3% ophthalmic solutions in on the most effective route of an- crease cultures and reach adequate patients undergoing photorefractive timicrobial administration for the concentrations to prevent and treat keratectomy.693 No differences were prevention of endophthalmitis. The most corneal pathogens.675,705 Ami- seen among preoperative, postopera- routes of antimicrobial administra- noglycosides alone687 or in com- tive, or contact lens cultures between tion used in ophthalmic procedures

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 235 ASHP Report Antimicrobial prophylaxis include preoperative topical antimi- and 17,318 patients received intra- shown to be safe and effective in low- crobial ophthalmic drops, addition cameral cefuroxime 1 mg at the end ering rates of endophthalmitis,671,673 of antimicrobials to the irrigation of the procedure. There were two decreasing bacterial organisms and solution, instillation of antimicrobials groups of patients excluded from CFUs in conjunctiva,667,675,691,692,698,700 intracamerally at the end of surgery, the analysis: protocol violators and achieving adequate concentra- subconjunctival injection of antimi- who received no prophylaxis and tions to be effective against most crobials, and postoperative topical patients who were enrolled in the ocular pathogens,705,706,708-710,719 with application of antimicrobials.6,684,702,717 ESCRS study. The overall rate of en- no notable adverse events.711-714 The ESCRS randomized con- dophthalmitis in analyzed patients Duration and timing. There are a trolled study mentioned above found was 35 cases in 36,743 procedures lack of clear evidence and no consen- that patients not receiving intracam- (0.95 per 1,000 cases). Of these, 27 sus on the appropriate duration and eral cefuroxime were approximately occurred in the subconjunctival timing of antimicrobial prophylaxis six times more likely to develop post- cefuroxime group (1.39 per 1,000 in ophthalmic procedures.6,684 Com- operative endophthalmitis.679,680,694 cases), and 8 occurred in the intra- monly reported times of antimicrobial Surveys of the impact of the ESCRS cameral group (0.46 per 1,000 cases) prophylaxis include preoperatively, study findings found that there was (OR, 3.01; 95% CI, 1.37–6.63; p = intraoperatively, at the end of the an increase in the use of intracam- 0.0068). procedure, and postoperatively.684 eral over subconjunctival cefuroxime Several studies found a lower rate Few studies have investigated the based on preliminary study results.703 of endophthalmitis with the addi- differences between the timing and For respondents who had not adopt- tion of intracameral cephalosporins duration of antimicrobial prophy- ed this practice, the reported reasons (cefazolin and cefuroxime) at the laxis regimens. Many of the regimens for not using intracameral cefurox- end of the surgical procedure after are used in combination, making it ime included the need for further routine perioperative and postopera- difficult to determine the optimal study, concerns about risk and cost tive topical antimicrobial prophylaxis timing and duration. Preoperative of therapy, the lack of a subconjunc- regimens.670,674 A case–control study antimicrobial timing reported in tival comparator group, the high rate revealed a 5.7 times increased likeli- the literature has ranged from one of endophthalmitis in the control hood of developing postoperative to multiple drops within an hour groups, concerns about statistical endophthalmitis with topical antimi- preoperatively on the day of the analysis, and questions regarding crobial prophylaxis only (including procedure671,673,679,680,692-694,698,703,709,710,716 the selection of cefuroxime due to gentamicin 0.3% and chlorhexidine or one to three days before the gaps in ophthalmic pathogen cover- 0.05%) compared with the addition procedure.667,698,700,703,708,710,712,714 age.695,697 There is no commercially of intracameral cefuroxime 1 mg to Two topical moxifloxacin regi- available cefuroxime formulation for the regimen in cataract procedure.677 mens were compared for conjunc- intracameral administration, which Both intracameral cephalosporins tival bacterial flora and aqueous was reported as one of the main bar- and moxifloxacin have been shown humor concentrations in a random- riers to use of this route. Concerns as safe, with no adverse events and no ized controlled study of patients regarding compounded intracameral effects on visual acuity and endothe- undergoing cataract procedures.691,719 antimicrobials expressed by survey lial cell counts.670,674,699,715,716 In one regimen, patients were ad- respondents included inflammation, One study involving healthy adult ministered moxifloxacin 0.5% four dilution errors, corneal endothelial volunteers found that orally admin- times a day beginning one day before injury, and the risk for bacterial con- istered levofloxacin and moxifloxacin the procedure plus one drop two tamination and infection. achieved adequate aqueous humor hours before the procedure (total of A retrospective cohort study com- concentrations to provide activ- five drops before the procedure); the pared the efficacy of intracameral ity against gram-positive and most other group received moxifloxacin cefuroxime versus subconjunctival gram-negative ocular pathogens 0.5% two hours before surgery and cefuroxime in reducing the rate of without adverse events.707 every 15 minutes for the first hour of endophthalmitis after cataract pro- The addition of subconjunctival the procedure (total of five drops). cedures at one center in northeast antimicrobials to existing topical an- There were no cases of postoperative England.718 A total of 19,425 patients timicrobial prophylaxis regimens has endophthalmitis up to six months received antimicrobial prophylaxis also been shown to reduce the rate after the procedure in any patient. with preoperative povidone–iodine and risk of endophthalmitis in in- Administration of moxifloxacin on 5% in the conjunctival sac and sub- traocular procedures compared with the day of the procedure was found conjunctival injection of cefuroxime topical antimicrobials alone.668,681,686 to result in a significant decrease in 50 mg at the end of the procedure, Topical antimicrobials have been median CFU compared with baseline

236 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis and was found (based on change in administration of the preoperative including Staphylococcus species and log CFU) to be more effective than antimicrobial and before povidone– gram-negative organisms, particu- antimicrobial administration on iodine, immediately before the pro- larly Pseudomonas species. the day before the procedure. Mean cedure, and at the conclusion of the Preoperative antisepsis with aqueous humor concentrations of procedure. Mean CFU counts did povidone–iodine is recommended, moxifloxacin at the beginning of the not significantly differ five days pre- based on available evidence. Appro- procedure were significantly higher operatively and immediately before priate topical antimicrobials include in the group who received the drug the procedure but were significantly commercially available neomycin– on the day of the procedure. higher in the control group at all polymyxin B–gramicidin solution A small, randomized controlled other time points. Neither outcomes or fluoroquinolones (particularly study compared aqueous humor of endophthalmitis nor patient fourth-generation agents) given as concentrations of levofloxacin and compliance with antimicrobial use one drop every 5–15 minutes for five ciprofloxacin in patients undergoing was reported. The study’s authors doses within the hour before the start a cataract procedure with routine concluded that three days of topical of the procedure (Table 2). The ad- phacoemulsification given as (1) one ofloxacin was more effective than addition of subconjunctival cefazolin or two drops four times daily for two ministration just one hour before the 100 mg or intracameral cefazolin days before the procedure, with the procedure in reducing the number of 1–2.5 mg or cefuroxime 1 mg at the last dose given immediately before positive bacterial cultures at several end of the procedure is optional. bedtime on the night before the time points perioperatively. While some data have shown that procedure, (2) five doses (one or two Numerous studies have evalu- intracameral antimicrobials may be drops) delivered every 10 minutes ated the efficacy of intracameral more effective than subconjunctival in the hour before the procedure, and subconjunctival injections of antimicrobials, there are no com- or (3) a combination of both dos- antimicrobials given at the end mercially available antimicrobials ing strategies.706 Aqueous humor of surgery.6,674,677,679-682,697,699,703,716,718 approved for these routes of admin- concentrations of levofloxacin were The most commonly reported dose istration. (Strength of evidence for significantly higher than those of of intracameral cefuroxime was 1 prophylaxis = B.) ciprofloxacin. Significantly higher mg,677,679,680,682,699,718 and the most doses of drug were delivered to the commonly reported subconjuncti- Orthopedic procedures aqueous humor in the group receiv- val dose was 50 mg.718 Doses of 2.5 Background. Orthopedic proce- ing same-day prophylaxis than in or 1 mg of intracameral cefazolin dures considered in these guidelines patients receiving levofloxacin or were studied,670,674 as were 250- and include clean orthopedic proce- ciprofloxacin two days before sur- 500-mg doses of intracameral moxi- dures (not involving replacement or gery. No cases of endophthalmitis floxacin.715,716 Postoperative dosing implantations), spinal procedures or ocular or systemic toxicities were strategies reported in the literature with or without instrumentation, reported. include four times daily for 3–7 repair of hip fractures, implanta- A randomized controlled study days667,670,671,673-675,679,680,692,711,712,715 and tion of internal fixation devices compared the effectiveness of topi- for up to 15 days713,714 or until the (screws, nails, plates, and pins), and cal ofloxacin in the reduction or bottle was empty.716 total-joint-replacement procedures. elimination of conjunctival bacterial Despite the lack of well-controlled Grade III open fractures (extensive flora when given as one drop every trials, the consequences of bacterial soft tissue damage and crushing) five minutes for three applications endophthalmitis support the use of are often associated with extensive one hour before the procedure alone prophylactic antimicrobials. No de- surgical-site contamination and are (control group) or combined with finitive studies have clearly delineated routinely managed with empirical ofloxacin one drop four times daily superiority of antimicrobial route, antimicrobial treatment and surgical for three days (study group) before timing, or duration. debridement, for which guidelines cataract procedures.688 No differences Recommendation. Due to the have been published separately.720 in positive conjunctival cultures were lack of robust data from trials, spe- Available guidelines recommend that seen between groups five days before cific recommendations cannot be antimicrobial prophylaxis in grade topical antimicrobials or before the made regarding choice, route, or I (clean wound with ≤1-cm lacera- administration of ofloxacin on the duration of prophylaxis. As a general tion) and grade II (clean wound with day of the procedure. Significantly principle, the antimicrobial prophy- >1-cm laceration without extensive higher positive culture rates were laxis regimens used in ophthalmic soft tissue damage) open fractures seen in the control group than in procedures should provide coverage be handled similarly to other clean the study group one hour after the against common ocular pathogens, orthopedic procedures.721-724

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 237 ASHP Report Antimicrobial prophylaxis

Between 2006 and 2008, SSIs were There is increasing concern re- crobials after the surgical procedure, reported nationally, based on risk cat- garding the emergence of SSIs due which may have led to invalid re- egory, in approximately 0.7–4.15 per to resistant microorganisms, spe- sults. The low rate of infection and 100 procedures for patients undergo- cifically VRE and MRSA in surgi- absence of serious morbidity failed ing spinal fusion, 0.72–2.3 per 100 cal patients. Several studies have to justify the expense or potential procedures in patients undergoing investigated MRSA colonization for toxicity and resistance associated laminectomy, 0.67–2.4 per 100 pro- and SSIs and evaluated the effect with routine use of antimicrobial cedures in patients undergoing hip of decolonization, including the prophylaxis in the setting of clean prosthesis, and 0.58–1.60 per 100 pro- use of topical mupirocin, in or- orthopedic procedures. cedures in patients undergoing knee thopedic procedures.150,157,741,749-753 Recommendations. Antimicrobial prosthesis.165 Postoperative SSI is one Mupirocin decolonization protocols prophylaxis is not recommended for of the most costly complications of as an adjunct to i.v. cephalosporin patients undergoing clean ortho- orthopedic procedures due to hospi- prophylaxis in orthopedic patients pedic procedures, including knee, tal readmissions, extended hospital resulted in significant decreases hand, and foot procedures, arthros- length of stay, the need for additional in nasal MRSA carriage150,751 and copy, and other procedures without procedures (often removal and reim- overall SSIs.157,750-752 Preopera- instrumentation or implantation plantation of implanted hardware), tive decolonization with intrana- of foreign materials. (Strength of convalescent or nursing home care sal mupirocin may have utility in evidence against prophylaxis = C.) between procedures, and significant patients undergoing elective or- If the potential for implantation of increases in direct hospital costs thopedic procedures who are foreign materials is unknown, the (e.g., prolonged antimicrobial thera- known to be colonized or infected with procedure should be treated as with py).725,726 Studies have found that the either MRSA or MSSA.150,151,157,741,749-755 implantation. estimated economic impact of one Readers are referred to additional deep SSI was $100,000 in hospital discussion in the Common Prin- Spinal procedures with and costs alone after hip arthroplasty and ciples section of these guidelines. without instrumentation $60,000 after knee arthroplasty.727-731 Background. Data support the In light of the serious consequenc- Clean orthopedic procedures not use of antimicrobial prophylaxis for es, antimicrobial prophylaxis is well involving implantation of foreign orthopedic spinal procedures with accepted in procedures involving the materials and without instrumentation, in- implantation of foreign materials.8,732 Background. In clean orthope- cluding fusions, laminectomies, and Prophylaxis is also indicated in spinal dic procedures, such as knee, hand, minimally invasive disk procedures, procedures without instrumentation, and foot procedures, and those to decrease the rate of postoperative where an SSI would pose catastroph- not involving the implantation of spinal infection.8,543,563,732,733,739,763-766 ic risks.726,733-738 foreign materials, the need for an- SSIs after orthopedic spinal proce- Organisms. Skin flora are the timicrobial prophylaxis is not well dures, including minimally invasive most frequent organisms involved established.738,749,756 Antimicrobial disk procedures, are associated with in SSIs after orthopedic procedures. prophylaxis in patients undergoing high morbidity. Invasion of the ep- The most common pathogens in diagnostic and operative arthroscop- idural space in organ/space SSIs is orthopedic procedures are S. aureus, ic procedures is controversial.6,757-760 of particular concern after spinal gram-negative bacilli, coagulase- The risks of SSI and long-term se- procedures.8,145,767 negative staphylococci (including quelae are low for procedures not SSI rates vary with the complexity S. epidermidis), and b-hemolytic involving implantation. of the procedure. One retrospective, streptococci.739-743 Spinal procedures Efficacy. The efficacy of antimi- multicenter study of 1274 adult pa- may be complicated by polymicro- crobial prophylaxis in clean ortho- tients found an overall SSI rate of bial infection that includes gram- pedic procedures was first investi- 0.22% with antimicrobial prophy- negative bacteria.740 gated in the middle part of the 20th laxis after minimally invasive spinal A contributing factor to SSIs in century. A number of these studies procedures (i.e., any spinal proce- arthroplasty is the formation of and reviews have since been found dures performed through a tubular bacterial biofilm, particularly with to be flawed, as patients were not retractor-type system).768 Procedures S. aureus and S. epidermidis, on inert randomized to treatment groups included simple decompressive pro- surfaces of orthopedic devices. Bac- and the timing and duration of cedures (such as microscopic or terial biofilm confers antimicrobial antimicrobial prophylaxis were not endoscopic discectomy or forami- resistance and makes antimicrobial studied.761,762 Further, patients were notomy or decompression of steno- penetration difficult.744-748 administered prophylactic antimi- sis), minimally invasive arthrodeses

238 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis with percutaneous instrumentation, ness of antimicrobial prophylaxis.732 including those caused by gram- and minimally invasive intradural Antimicrobials studied included negative bacteria.563,769 procedures. The SSI rate in patients single-dose or multidose regimens of Clindamycin and vancomycin receiving antimicrobial prophylaxis <24 hours’ duration of cephaloridine have adequate activity against the undergoing spinal procedures with (a first-generation cephalosporin most common pathogens involved in instrumentation has ranged from no longer available in the United orthopedic procedures and would be 2.8% to 9.7%.165,764,765,769,770 Monoseg- States), vancomycin and gentamicin, acceptable alternatives under certain mental instrumentation has a report- cefazolin with and without genta- circumstances, such as prophylaxis ed SSI rate of <2%, compared with micin, piperacillin, and oxacillin. for patients with a b-lactam allergy. 6.7% for instrumentation at multiple The pooled SSI rate with antimicro- Vancomycin should be included with levels.771 bial prophylaxis was 2.2%, compared cefazolin or used as an alternative Several case–control studies of with 5.9% in controls (OR, 0.37; agent for routine antimicrobial pro- adults undergoing spinal procedures 95% CI, 0.17–0.78; p < 0.01). One phylaxis for patients who are known with and without instrumentation randomized controlled study of 1237 to be colonized with MRSA.6,8,41,733,781 have found the following notable adult patients undergoing spinal Duration. The majority of avail- patient-related risk factors for SSI: procedures to repair a herniated disk able studies of antimicrobial pro- prolonged preoperative hospitaliza- (hemilaminectomy, laminectomy, phylaxis in spinal procedures have tion,771 diabetes,767,772-775 elevated flavectomy, spondylosyndesis) found used single doses or regimens of serum glucose concentration (>125 no significant difference in the rate of <24 hours’ duration.732 There is no mg/dL preoperatively [within 30 SSIs between single-dose cefuroxime high-quality evidence supporting a days] or >200 mg/dL postopera- 1.5 g i.v. (1.3%) and placebo (2.9%) duration of >24 hours,782 and some tively),773 older age,767,776 smoking and given within 60 minutes before surgi- sources recommend only a single alcohol abuse,776 previous procedure cal incision. No significant difference preoperative dose.8,769,778 complicated by infection,774-776 and was seen between treatment groups Pediatric efficacy. While no stud- obesity.770-775,777 Procedure-related for incisional SSIs (0.98% and 1.12%, ies have evaluated the efficacy of an- risk factors include extended dura- respectively) or deep SSIs (0.33% and timicrobial prophylaxis in pediatric tion of procedure (defined in stud- 0.32%, respectively), but the differ- patients undergoing spinal proce- ies as two to five hours or greater ence in organ/space infections was dures with or without instrumenta- than five hours,775 greater than significant between groups (0% and tion, the incidence and risk factors three hours,771 and greater than five 1.44%, respectively; p < 0.01).778 for SSIs in this population have been hours776), excessive blood loss (>1 Choice of agent. There is no clearly reported. The frequencies of SSIs in L),771,775 staged procedure,776 multilev- superior antimicrobial agent or regi- pediatric patients undergoing spinal el fusions,777 foreign-body placement men for spinal procedures.563,769 The fusion were 3.5% (<18 years old),783 (e.g., screw, rod, plate),767 combined antimicrobials most often studied for 3.8% (<19 years old),784 4.4% (ages anterior and posterior fusion,776 prophylaxis in orthopedic procedures 1–22 years old), and 5.2% (<17 years and suboptimal antimicrobial tim- are first-generation cephalosporins, old)764 for varying conditions, in- ing (>60 minutes before or after particularly cefazolin. Cefazolin has cluding Scheuermann’s kyphosis,784 incision).773 A significant decrease in been noted as a suitable agent for myelodysplasia,764 idiopathic scolio- SSIs was seen with procedures at the spinal procedures with its spectrum sis,783,785 neuromuscular scoliosis,785 cervical spine level772,773 or with an of activity (e.g., against Staphylococ- kyphosis,783 and spondylolisthesis.783 anterior surgical approach.775 cus species and gram-negative bacilli The majority of patients in studies Efficacy. Despite the lack of com- such as E. coli) and adequate tissue121 reporting antimicrobial prophylaxis parative studies evaluating prophy- and disk concentrations.779,780 received cefazolin, vancomycin, or laxis for spinal procedures with and Second- and third-generation clindamycin.764,783,785 without instrumentation (implanta- cephalosporins offer no major ad- Risk factors for SSIs after spinal tion of internal fixation devices), vantages over first-generation agents. procedures with instrumentation antimicrobial prophylaxis is recom- Their routine use is not recom- in a pediatric population include mended due to the associated mor- mended due to their higher cost myelodysplasia,764 procedure at the bidity and assumed costs of SSIs.771 and potential to promote resistance, sacral spine, obesity,785 ASA classifica- A meta-analysis of six studies with particularly among health-care- tion of >2, a complex medical condi- 843 patients undergoing spinal pro- associated gram-negative bacilli.8 tion (including spinal bifida, cerebral cedures (types of procedures were Broader coverage may be considered palsy, Marfan syndrome, achondro- not differentiated in the analysis) for instrumented fusion due to the plasia, osteogenesis imperfecta, other demonstrated an overall effective- risk of polymicrobial infections, unspecified genetic disease, muscular

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 239 ASHP Report Antimicrobial prophylaxis dystrophy, spinal muscular atrophy, Hip fracture repair Second- and third-generation cepha- or other debilitating myopathies),783 Background. Data support the use losporins have not been shown to and previous spinal procedures. One of antimicrobial prophylaxis for hip offer clear advantages over first- study found a decreased risk of infec- fracture repair to reduce the rate of generation agents. These agents are tion with hypothermia (core body SSIs, particularly in procedures that not recommended for routine use temperature of <35.5 °C for the du- involve internal fixation (e.g., nails, due to their higher cost, potential to ration of the procedure).785 screws, plates, wires). SSIs after hip promote resistance, and association Two studies found suboptimal an- fracture repair can result in extensive with adverse events (e.g., C. difficile- timicrobial prophylaxis as a risk fac- morbidity, including prolonged and associated diarrhea).8,790,792 tor for SSIs in spinal procedures.764,783 repeated hospitalization, sepsis, per- Alternative regimens may be Optimal antimicrobial prophylaxis sistent pain, device replacement, and needed for institutions with highly was defined as cefazolin 20 mg/kg possible death.726,739,786-790 resistant organisms, such as MRSA or (up to 2 g) given within 30 minutes764 Efficacy. The efficacy of anti- C. difficile. Success in decreasing rates or 60 minutes783 before surgical inci- microbial prophylaxis in hip frac- of C. difficile-associated disease and sion, vancomycin 10 mg/kg (up to 1 ture repair has been illustrated in mortality was seen in a single-center g) given within 60 minutes783 or 150 two meta-analyses.787,788 One meta- study with the antimicrobial pro- minutes764 before surgical incision, analysis of 15 hip fracture procedure phylaxis regimen change from three or clindamycin 10 mg/kg (up to 600 trials (the majority of procedures doses of cefuroxime790,792 to a single mg) given within 60 minutes before involved closed, proximal femoral, preoperative dose of cefuroxime surgical incision.783 Intraoperative or trochanteric fractures with inter- plus gentamicin.792 In another study, redosing was defined as appropriate nal fixation) demonstrated that any C. difficile-associated disease de- for cefazolin if administered for pro- dose and duration of prophylaxis creased after the prophylaxis regimen cedures lasting more than four hours are superior to no prophylaxis with was changed from cefuroxime to and for vancomycin or clindamycin respect to preventing SSIs (deep amoxicillin–clavulanate.790 for procedures lasting more than and superficial SSIs were analyzed Clindamycin and vancomycin six hours in one study783 and for together).787 The rate of SSIs was have adequate activity against the cefazolin administered every eight 10.4% in controls versus 5.39% in most common pathogens involved in hours in the other study.764 A third treatment groups. A second meta- orthopedic procedures and would be study found that use of clindamycin analysis of 22 studies reiterated the acceptable alternatives under certain as the perioperative antimicrobial efficacy of antimicrobial prophylaxis circumstances, such as prophylaxis increased the risk of SSI.785 in fracture procedures.788 The analy- for patients with a b-lactam allergy. Recommendations. Antimicro- sis included the same hip fracture Vancomycin should be included with bial prophylaxis is recommended for studies examined in the first meta- cefazolin or used as an alternative orthopedic spinal procedures with analysis, with additional studies of agent for routine antimicrobial pro- and without instrumentation. The long-bone fracture repair (i.e., closed phylaxis for patients who are known recommended regimen is cefazolin ankle fracture and other closed to be colonized with MRSA.6,8,41,733,781 (Table 2). (Strength of evidence for fractures, some noted with internal Duration. For effective prophy- prophylaxis in orthopedic spinal fixation). This second meta-analysis laxis, the MIC of the antimicrobial procedures = A.) Clindamycin and reviewed 10 studies of 1896 patients needs to be exceeded at the target site vancomycin should be reserved as receiving a preoperative and two or from the moment of incision until alternative agents as described in the more postoperative doses of a par- surgical-site closure.788 Two meta- Common Principles section. If there enteral antimicrobial compared with analyses demonstrating the efficacy are surveillance data showing that a placebo or with no treatment. The of antimicrobial prophylaxis in long- gram-negative organisms are a cause authors found a relative risk of deep bone and hip fracture procedures also of SSIs for the procedure, practi SSIs of 0.36 (95% CI, 0.21–0.65) and showed that multiple perioperative tioners may consider combining a relative risk of superficial SSIs of doses did not offer an advantage over clindamycin or vancomycin with an- 0.48 (95% CI, 0.28–0.81) associated a single preoperative dose.787,788 These other agent (cefazolin if the patient with antimicrobial use. studies support a duration of antimi- is not b-lactam allergic; aztreonam, Choice of agent. The antimicro- crobial prophylaxis of ≤24 hours. gentamicin, or single-dose fluoro- bials most often studied for pro- Recommendations. The recom- quinolone if the patient is b-lactam phylaxis in orthopedic procedures mended regimen in hip fracture re- allergic). Mupirocin should be given are first-generation cephalosporins pair or other orthopedic procedures intranasally to all patients known to due to their ease of administration, involving internal fixation is cefazo- be colonized with S. aureus. low cost, and safety profile.787,788,791 lin. Clindamycin and vancomycin

240 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis should be reserved as alternative Common risk factors for prosthet- or revision. The SSIs were defined agents, as described in the Com- ic joint infection748 include advanced as visible purulent exudates at the mon Principles section. If there are age; obesity; diabetes mellitus; corti- surgical site (deep or superficial) in surveillance data showing that gram- costeroid use; malignancy; rheuma- the included studies. Seven studies negative organisms are a cause of SSIs toid arthritis; previous arthroplasty (n = 3065 patients) pooled to com- for the procedure, practitioners may on the same joint; arthroplasty un- pare antimicrobial prophylaxis with consider combining clindamycin or dertaken to treat a fracture; type of placebo found a relative risk reduc- vancomycin with another agent (ce- joint replaced (e.g., risk is greater for tion of SSIs of 81%. fazolin if the patient is not b-lactam the knee than the hip); perioperative Choice of agent. There are no data allergic; aztreonam, gentamicin, or surgical-site complications, includ- supporting superiority of one class of single-dose fluoroquinolone if the ing superficial SSI; hematoma; and antimicrobials over another for an- patient is b-lactam allergic). Mupi- persistent surgical-site drainage. timicrobial prophylaxis in total joint rocin should be given intranasally to Operative risk factors include ASA replacement. A meta-analysis of stud- all patients with documented colo- classification of≥ 3, duration of pro- ies, mainly in total hip or total knee nization with S. aureus. (Strength of cedure exceeding the 75th percentile replacement, found no difference in evidence for prophylaxis = A.) for the procedure or exceeding three SSIs between cephalosporins with tei- hours, surgical site classified as con- coplanin (not available in the United Total joint replacement taminated or dirty, and no systemic States) in five studies with 2625 Background. In 2005, more antimicrobial prophylaxis. Excluding patients, cephalosporins and peni- than 750,000 hip or knee replace- the presence of a systemic antimi- cillin derivatives in three studies of ments were performed in the United crobial, patients with these operative 386 patients, and first- and second- States.793 The reported frequency of risk factors are at the greatest risk of generation cephalosporins in eight SSIs complicating hip, knee, elbow, developing an SSI. studies of 2879 patients.801 Selection ankle, or shoulder replacement A contributing factor to SSIs in should be based on cost, availability, ranges from 0.6% to 12%.743,786,794-797 arthroplasty is the formation of bacte- and local resistance patterns. First- SSI rates as high as 11% after hip rial biofilm, particularly with S. aureus generation cephalosporins are the replacement and 12% after elbow and S. epidermidis, on inert surfaces agents most commonly studied and replacement have been reported.786,797 of orthopedic devices to confer anti- used for antimicrobial prophylaxis in However, for hip and knee replace- microbial resistance and difficulty in joint replacement procedures. ments, the most common joint ar- antimicrobial penetration.744-748 Clindamycin and vancomycin throplasties, infection rates are typi- Efficacy. The majority of stud- have adequate activity against the cally less than 2%.165 ies that have evaluated antimicro- most common pathogens involved in The introduction of antimicrobial prophylaxis in joint replacements orthopedic procedures and would be bial prophylaxis, stringent infection- have been conducted in patients acceptable alternatives under certain control protocols, and the use of undergoing total hip or total knee ar- circumstances, such as prophylaxis ultraclean operating rooms has led throplasty.801 There is a lack of efficacy for patients with a b-lactam allergy. to a substantial reduction in SSI rates data involving elbow, shoulder, and Vancomycin should be included (to ≤1%).734,786,796,798,799 Postoperative ankle arthroplasty; however, the same with cefazolin or used as an alterna- prosthetic joint infection is an organ/ antimicrobial prophylaxis principles tive agent for routine antimicrobial space SSI that occurs early (within 3 can be applied. In light of the serious prophylaxis in institutions that have months postoperatively), is delayed potential consequences, antimicro- a high prevalence of MRSA SSIs and (3–12 months postoperatively), or bial prophylaxis is well accepted in for patients who are known to be col- occurs late (>12 months after sur- procedures involving the implanta- onized with MRSA.6,8,41,733,781 Readers gery).748 These infections frequently tion of foreign materials.8,543,732,733 are referred to the section on implan- require removal of the prosthesis, a A meta-analysis supports the use tation of internal fixation devices for prolonged course of antimicrobials, of antimicrobial prophylaxis for SSI further discussion of antimicrobial and one- or two-stage reimplanta- reduction in patients undergoing prophylaxis choice. tion of the prosthesis and may result total joint replacement.801 Of the Antimicrobial-laden bone cement. in permanent disability.796,800 Studies 26 randomized controlled studies The use of antimicrobial-laden bone have shown an estimated economic examined, 24 included patients un- cement in conjunction with i.v. an- impact of one deep SSI of $100,000 dergoing total hip or total knee ar- timicrobial prophylaxis is common in hospital costs alone after hip arthroplasty. The meta-analysis noted worldwide, particularly for the pre- throplasty and $60,000 after knee that the studies did not clearly state vention of infection in primary hip arthroplasty.727-731 if the arthroplasties were primary and knee arthroplasties.802-806 FDA

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 241 ASHP Report Antimicrobial prophylaxis has approved premixed aminogly- Recommendations. The recom- antimicrobial prophylaxis in uro- coside (i.e., gentamicin and tobra- mended regimen for patients under- logic procedures.817,826-828 Additional mycin) in bone cement products for going total hip, elbow, knee, ankle, urologic operation-specific risk fac- use in hip, knee, or other joints in or shoulder replacement is cefazolin. tors include length of postoperative second-stage revision of total joint Clindamycin and vancomycin should catheterization,829 mode of irrigation arthroplasty.807 The products are not be reserved as alternative agents, as (closed versus open), and postopera- approved for prophylaxis in primary described in the Common Principles tive pyuria.821 joint replacement procedures. While section. If there are any surveillance Organisms. E. coli is the organism antimicrobial bone cement has not data showing that gram-negative most commonly isolated in patients been shown to be superior to i.v. organisms are a cause of SSIs for the with postoperative bacteriuria; how- antimicrobials,808,809 there is evidence procedure, practitioners may consid- ever, other gram-negative bacilli and that supports the combination of user combining clindamycin or vanco- enterococci may also cause infec- ing antimicrobial-laden bone cement mycin with another agent (cefazolin tion.818,821,827,830-839 Organisms such together with systemic antimicrobial if the patient is not b-lactam allergic; as S. aureus, coagulase-negative prophylaxis. aztreonam, gentamicin, or a single- Staphylococcus species, and group A Although the evidence for the dose fluoroquinolone if the patient is Streptococcus species are also a con- prophylactic use of antimicrobial- b-lactam allergic). Mupirocin should cern in procedures entering the skin laden bone cement in primary joint be given intranasally to all patients with or without entering the urinary arthroplasty looks favorable, a recent with documented colonization with tract.818,827,830-832,838,840,841 There is also multicenter evaluation of risk fac- S. aureus. (Strength of evidence for some concern with biofilm-forming tors for SSI in patients undergoing prophylaxis = A.) bacteria (S. epidermidis and P. aeru- total hip arthroplasty did not find ginosa) in patients with prosthesis that use of antimicrobial-laden bone Urologic procedures implantation.842 cement reduced the risk for infec- Background. The goals of anti- Efficacy. The efficacy of antimi- tion.95 In addition, questions remain microbial prophylaxis in urologic crobial prophylaxis in select urologic regarding the risk for antimicrobial procedures are the prevention of procedures has been investigated in resistance and allergy, as well as the bacteremia and SSIs and the preven- several clinical trials. Of note, many increased cost.41,802-807,810-813 Readers tion of postoperative bacteriuria.59 of these placebo-controlled studies are referred to reviews of this topic Postoperative urinary tract infections have excluded patients with risk fac- for additional information about tis- (UTIs) are the main concern for tors for infection, those requiring sue penetration, clinical application, morbidity in patients after urologic antimicrobial prophylaxis for another and safety.805,810-815 procedures.817,818 Bacteriuria, defined indication (e.g., infective endocardi- Duration. The duration of prophy- as >103 or >104 CFU/mL in symp- tis), and those with preoperative UTI laxis in joint replacement procedures tomatic UTI and >105 CFU/mL in or bacteriuria. has been controversial. More recent asymptomatic bacteriuria, within 30 The efficacy of antimicrobial pro- data and clinical practice guidelines days postoperatively is a frequent pri- phylaxis in clean procedures among do not support prophylaxis beyond mary outcome in urologic procedure patients at low risk of complications 24 hours.6,41,133,723 Studies involving studies.819-825 The benefits of prevent- has been variable. One randomized, total hip replacement have used an- ing postoperative bacteriuria are not placebo-controlled study of oral anti- timicrobials for 12 hours to 14 days clearly known.825 microbials in 2083 patients undergo- postoperatively.726,734-737,816 A duration In addition to general risk factors ing flexible cystoscopy found a posi- of 24 hours was supported in a ran- discussed in the Common Prin- tive urine culture (bacteriuria with domized trial of 358 patients under- ciples section of these guidelines, >105 CFU/mL) in 9.1% of patients going total hip arthroplasty, total knee urologic-specific risk factors include receiving placebo, 4.6% of patients arthroplasty, or hip fracture repair anatomic anomalies of the urinary receiving trimethoprim, and 2.8% that compared prophylaxis that lasted tract,818 urinary obstruction,826 uri- of patients receiving ciprofloxacin.839 24 hours versus 7 days of either naf nary stone,817,825,826 and indwelling The rates of bacteriuria compared cillin or cefazolin started 20 minutes or externalized catheters.817,818,822,826 with baseline were significantly higher before the procedure.816 The differ- Preoperative UTI, particularly if re- with placebo and significantly lower ence in SSI rates between groups was current, is recognized as a high-risk with use of antimicrobials compared not significant. There is no evidence factor for postoperative infection, with placebo. A randomized, placebo- of benefit of antimicrobial admin- which is typically treated before pro- controlled study of 517 patients istration until all drains or catheters cedures and is a common exclusion undergoing prostate brachytherapy are removed.32,41,133 criterion from studies of efficacy of found no significant difference in

242 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis postimplantation epididymitis with trimethoprim) compared with pla- been extrapolated from other major or without antimicrobial prophylaxis cebo (30%) (p = 0.009).822 intraabdominal procedures. (0.4% and 1.5%, respectively).843 A Three randomized, placebo- Choice of agent. No single antimi- meta-analysis of eight randomized, controlled studies of patients un- crobial regimen appears superior for placebo-controlled or no-treatment- dergoing transrectal needle biopsy urologic procedures. A wide range controlled studies with 995 patients of the prostate found significant dif- of antimicrobial regimens, including undergoing urodynamic studies ferences in infectious complications cephalosporins,658,835,836,843,849-855 ami- found a decrease in bacteriuria with (including bacteriuria, positive urine noglycosides,856,857 piperacillin– antimicrobial prophylaxis (OR, 0.39; cultures, and UTI) in patients treated tazobactam,849,858,859 trimethoprim– 95% CI, 0.24–0.61).820 The number with single doses of oral antimi- sulfamethoxazole,822,838,860 trimeth needed to treat was 13 to prevent one crobial prophylaxis compared with oprim,839 nitrofurantoin,861 and episode of asymptomatic bacteriuria placebo.819,837,838 These three studies fluoroquinolones,819,821,822,824,831, using a pooled rate of 13.7% for support the routine use of antimicro- 835-837,839,840,843,848,851,853-855,862,863 have bacteriuria. One study found that bial prophylaxis in all patients under- been evaluated in urologic proce- not using antimicrobial prophylaxis going transrectal needle biopsy of the dures. The efficacy of fluoroquino- was a significant risk factor for bac- prostate. Of note, all patients under- lones for antimicrobial prophylaxis teriuria caused by urinary dynamic going transrectal needle biopsy of the in urologic surgical procedures has studies.821 prostate received a cleansing enema been well established. One study Antimicrobial prophylaxis has before the procedure.819,837,838 Use of found better reduction of bacteriuria been studied in urologic procedures MBP has been reported in urologic with either ciprofloxacin or trim- involving entry into the gastrointesti- procedures that involve entering the ethoprim compared with placebo,839 nal tract, with the majority of the liter- gastrointestinal tract (e.g., urinary while other studies found no differ- ature on transurethral resection of the diversion).844,846 ence in efficacy between a fluoro- prostate (TURP) and prostate biopsy. The use of antimicrobial pro- quinolone and sulfamethoxazole– Two large meta-analyses have sug- phylaxis in patients undergoing ex- trimethoprim, both of which were gested prophylactic antimicrobials tracorporeal shock wave lithotripsy better than placebo.822,838 No differ- may be effective in all patients under- (ESWL) and ureterorenoscopy is ences were found in studies between going TURP, including low-risk pa- supported by the results of a meta- oral or i.v. fluoroquinolones (cipro- tients and those with preoperatively analysis847 and a small randomized floxacin or ofloxacin) compared with sterile urine.844,845 One meta-analysis controlled trial.848 The meta-analysis i.v. or intramuscular cephalosporins of 32 trials with 4260 patients found included eight randomized con- (ceftriaxone, cefotaxime, or cefazo- that prophylactic antimicrobials trolled trials with 885 patients and lin) and intramuscular penicillin decreased the combined bacteriuria six clinical case series involving 597 (piperacillin–tazobactam) in various (>105 CFU/mL) event rate from 26% patients undergoing ESWL.845 The urologic procedures.835,836,851,854,855,858 to 9.1%, for a relative risk reduction overall rate of UTI in the random- In several studies, fluoroquinolones of 65% (95% CI, –55 to –72), and ized controlled trials ranged from were administered orally, which ap- the combined clinical septicemia 0% to 7.7% with antimicrobial pro- pears to be feasible in patients un- episode rate from 4.4% to 0.7% in phylaxis and from 0% to 28% in the dergoing procedures not involving TURP patients, including low-risk control groups (relative risk, 0.45; opening the urinary or gastrointes- patients.846 Another meta-analysis 95% CI, 0.22–0.93). A randomized, tinal tract, when the i.v. route would of 28 trials that included a total of placebo-controlled study of 113 be preferred.822,836,838,851,855,858 Recently, 4694 patients found prophylactic patients undergoing ureterorenos- resistance to fluoroquinolones has antimicrobials decreased the post- copy found a rate of postoperative been emerging; the fact that most of TURP rate of bacteriuria, fever, and bacteriuria of 1.8% with antimicro- the literature was published before bacteremia, as well as the need for bial prophylaxis and 12.5% without resistance became prevalent should additional postoperative antimicro- (p = 0.0026).848 No patients had be considered, since resistance may bials.847 An additional multicenter, symptomatic UTI or inflammation decrease the relevance of these stud- open-label, randomized, active- and complications of the urogenital ies.836,846,847,858,864 Local resistance pat- placebo-controlled trial in patients tract postoperatively. terns to fluoroquinolones, particu- with sterile urine undergoing TURP There are no studies of antimi- larly with E. coli, should be evaluated found a decreased rate of bacteriuria crobial prophylaxis in major open to help guide antimicrobial selection. (≥5 CFU/mL) with antimicrobial or laparoscopic procedures (cystec- Broad-spectrum antimicrobials, prophylaxis (21% with levofloxacin tomy, radical prostatectomy, and such as third-generation cephalo- and 20% with sulfamethoxazole– nephrectomy); therefore, data have sporins and carbapenems, are no

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 243 ASHP Report Antimicrobial prophylaxis more effective than first- or second- bacteriuria or UTI should be treated ditions.868 As a result, antimicrobial generation cephalosporins, aminogly- before the procedure, when possible, prophylaxis is widely used in proce- cosides, or oral agents (trimethoprim– to reduce the risk of postoperative in- dures that involve implantation of sulfamethoxazole, nitrofurantoin, or fection. For patients undergoing low- prosthetic material and procedures fluoroquinolones) and should be re- er urinary tract instrumentation with for which there is greater risk of served for patients with active infec- risk factors for infection, the use of a infection, such as aneurysm repair, tion or who require additional cover- fluoroquinolone or trimethoprim– thromboendarterectomy, and vein age for intestinal organisms.6,826,827 sulfamethoxazole (oral or i.v.) or bypass.6,41,867,869 Patients undergoing Their routine use is not recom- cefazolin (i.v. or intramuscular) is brachiocephalic procedures (e.g., mended due to their higher cost recommended (Table 2). For patients carotid endarterectomy, brachial and potential to promote resistance, undergoing clean urologic proce- artery repair) without implantation particularly among health-care- dures without entry into the urinary of prosthetic graft material do not associated gram-negative bacilli.8 tract, cefazolin is recommended, with appear to benefit from routine anti- Duration. While longer durations of vancomycin or clindamycin as an al- microbial prophylaxis.6,41,867,870 postoperative prophylaxis (up to ternative for those patients allergic to Risk factors for postoperative three weeks) have been stud- b-lactam antimicrobials. For patients SSI in patients undergoing vascular ied,856,858,860,861 more-recent data sup- undergoing clean urologic proce- procedures include lower-extremity port the use of shorter durations dures with entry into the urinary sites, delayed procedures after hos- (i.e., a single dose or less than tract, cefazolin is recommended, with pitalization, diabetes mellitus, and a 24 hours’ duration) in urologic alternative antimicrobials to include history of vascular or aortocoronary procedures.658,817,818,823,824,826,831, a fluoroquinolone, the combination bypass procedures.871,872 Currently, 832,834,836,846,853,857,859,862,865,866 Based on of an aminoglycoside plus metroni- prospective data from well-designed bioavailability, oral antimicrobi- dazole, or an aminoglycoside plus studies on prophylaxis for endovas- al prophylaxis should be admin- clindamycin. For clean-contaminated cular stenting do not exist. However, istered 1–2 hours before surgi- procedures of the urinary tract (often if prophylaxis is desired, the same cal incision or start of the proce- entering the gastrointestinal tract), antimicrobials and short duration dure.817,819-822,824,826,836,838,840,848,851,855 antimicrobials as recommended of therapy used for open vascular Pediatric efficacy. Limited data on for elective colorectal surgery are procedures should be given. Risk antimicrobial prophylaxis are avail- recommended. This would gener- factors that warrant consideration of able for pediatric patients undergo- ally include the combination of prophylaxis in patients undergoing ing urologic procedures. One pro- cefazolin with or without metroni- endovascular stenting include prospective, open-label, nonrandomized dazole, cefoxitin, or, for patients with longed procedures (more than two study of boys undergoing hypospa- b-lactam allergy, a combination of hours), reintervention at the surgical dias repair with tabularized incision either a fluoroquinolone or amino- site within seven days, vascular stent plate urethroplasty allocated patients glycoside given with either metroni- placement in the groin through a to receive cefonicid (no longer avail- dazole or clindamycin. The medical hematoma or sheath, procedures in able in the United States) with one literature does not support con- immunosuppressed patients, and i.v. dose before the procedure only or tinuing antimicrobial prophylaxis the presence of another intravascular the addition of oral cephalexin three until urinary catheters have been prosthesis.873-877 times daily starting on postopera- removed. See the colorectal proce- Organisms. The predominant tive day 1 until 2 days after catheter dures section of these guidelines organisms involved include S. aureus, removal (median, 8.3 days).833 More for recommendations pertaining to S. epidermidis, and enteric gram- patients in the single-dose group had procedures entering the gastrointes- negative bacilli. MRSA is an emerg- bacteriuria and complications (ure- tinal tract. (Strength of evidence for ing organism of concern. throcutaneous fistula and meatal ste- prophylaxis = A.) Several studies evaluated the nosis); however, the rate of infection rate of colonization, carriage, and and infection-related complications Vascular procedures infection with MRSA in patients did not significantly differ between Background. Infection after vas- undergoing various vascular proce- groups. cular procedures occurs with low fre- dures.878-884 Independent risk factors Recommendations. No antimicro- quency but can be associated with ex- for MRSA infection included MRSA bial prophylaxis is recommended for tensive morbidity and mortality.867,868 colonization, open abdominal aortic clean urologic procedures in patients Postoperative infections involving aneurysm, tissue loss, and lower- without risk factors for postoperative vascular graft material can result in limb bypass.878 Patients who have infections. Patients with preoperative limb loss and life-threatening con- or develop MRSA infections before

244 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis vascular procedures have increased tients undergoing permanent vascu- clusters or in patients with b-lactam risk of inhospital death, intensive lar access placement demonstrated an allergy.6,8,41 Clindamycin may be an care unit admission, repeat surgeries, upper-extremity prosthetic polytet- acceptable alternative to vancomycin, increased length of stay, and delayed rafluoroethylene graft infection rate though local antimicrobial resis- wound healing, compared with pa- of 6% with placebo compared with tance patterns should be taken into tients without infections.880-883 1% with vancomycin (p = 0.006).869 account. Efficacy. Prophylactic antimi- Choice of agent. Cefazolin remains An aminoglycoside may be added crobials decrease the rate of infec- the preferred and most cost-effective to vancomycin for the addition of tion after procedures involving the prophylactic agent for use in vascular aerobic gram-negative bacilli cover- lower abdominal vasculature and procedures.6,8,41,872,886,887 There was age if the procedure involves the procedures required to establish di- no significant difference in infection abdominal aorta or a groin incision, alysis access. The follow-up time for rates between cefazolin and cefu- due to the potential for gastrointesti- patients with late surgical-site com- roxime in patients undergoing ab- nal flora. See the Common Principles plications was at least once after hos- dominal aortic and lower-extremity section of these guidelines for further pital discharge (not further defined) peripheral vascular procedures,886 be- discussion of the use of vancomy- for most studies,829,865,871,885-887 at one tween cefazolin and cefamandole (no cin. Alternative antimicrobials for month,869,871,888,889 at six months,872 longer available in the United States) b-lactam-allergic patients receiving and at three years.138 in patients undergoing aortic or in- vancomycin may include a fluoro- A meta-analysis of 10 randomized frainguinal arterial procedures,887 or quinolone or aztreonam.6 controlled trials in patients undergo- between cefazolin and ceftriaxone in Duration. A meta-analysis of ing peripheral arterial reconstruction patients undergoing arterial recon- three randomized controlled stud- with biological or prosthetic graft struction involving infraclavicular ies involving vascular procedures, procedures found an overall consis- sites.872 including lower-limb reconstruction tent reduction in SSIs with systemic A multicenter, randomized, and open arterial procedures, found antimicrobial prophylaxis compared double-blind, prospective trial of no additional benefit of continuing with placebo (relative risk, 0.25; 95% 580 patients undergoing arterial prophylactic antimicrobials for over CI, 0.17–0.38; p < 0.00001).890 An procedures involving the groin who 24 hours postoperatively compared overall reduction was found among received either two doses of cipro- with no more than 24 hours (relative 5 studies evaluating early graft in- floxacin 750 mg orally or three doses risk, 1.28; 95% CI, 0.82–1.98).890 fection (relative risk, 0.31; 95% CI, of cefuroxime 1.5 g i.v. on the day A randomized, double-blind 0.11–0.85; p = 0.02), though no of the procedure found an SSI rate study compared infection rates of individual study found a significant of 9.2% (27 patients) and 9.1% (26 a one-day and a three-day course reduction in SSIs. patients), respectively, within 30 days of cefuroxime with placebo in 187 The largest study included in the of the procedure889 Although oral patients undergoing peripheral vas- meta-analysis above was a random- ciprofloxacin was shown to be as ef- cular procedures.888 The infection ized, prospective, double-blind, fective as i.v. cefuroxime, this study rates were 16.7%, 3.8%, and 4.3% in placebo-controlled study of patients did not address concerns about resis- the placebo, one-day, and three-day undergoing peripheral vascular pro- tance with routine use of fluoroquin- groups, respectively. The difference cedures (n = 462). The infection rate olones.891 Therefore, i.v. cefazolin in the infection rates between the was significantly lower with cefazolin remains the first-line agent for this one- and three-day groups was not than with placebo (0.9% and 6.8%, indication. The efficacy of oral agents significant. respectively).885 Four deep graft infor prophylaxis needs to be further A randomized controlled study fections were observed in the placebo evaluated. compared one day and five days of group; none occurred in the patients There are limited data regarding amoxicillin–clavulanate 1.2 g in 100 who received cefazolin. No infections the choice of an antimicrobial for patients undergoing 108 lower-limb were observed in patients who un- b-lactam-allergic patients undergo- reconstruction procedures.892 No dif- derwent brachiocephalic (n = 103), ing vascular procedures. The main ference was seen in the postoperative femoral artery (n = 56), or popliteal alternative agents are vancomycin SSI rate between groups (9 patients (n = 14) procedures. and clindamycin, since prophy- [16%] and 12 patients [23%], respec- Patients undergoing vascular laxis is largely directed against gram- tively). The study authors selected access procedures for hemodialysis positive cocci. Vancomycin can also the agent based on extended spec- may benefit from the administration be used for prophylaxis in institu- trum of activity and good tissue pen- of antistaphylococcal antimicrobials. tions with MRSA or methicillin- etration. However, they concluded A placebo-controlled study of 408 pa- resistant S. epidermidis (MRSE) that due to the high rate of infection

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 245 ASHP Report Antimicrobial prophylaxis observed, the use of antimicrobial plant recipients are at high risk for surgical prophylaxis based on the prophylaxis might not be as effective infections due to the complexity of best available literature. Antimicro- as once thought. the surgical procedures, donor- or bial surgical prophylaxis practice will A randomized controlled study recipient-derived infections, reacti- vary considerably among transplan- compared ticarcillin–clavulanate 3.1 vation of recipient-associated latent tation centers throughout the United g given as a single dose at induction infections, preoperative recipient States, based on the organ involved, of anesthesia with multiple doses colonization, exposure to commu- preexisting recipient and donor given at induction and every 6 hours nity pathogens, and opportunistic infections, and local antimicrobial postoperatively until venous access infections due to immunosuppres- susceptibilities.894-897 lines were removed or a maximum sion.894-897 Infections occur more Heart transplantation. Back- of 20 doses (total of five days) in frequently in the first year after trans- ground. Heart transplantation is an patients undergoing open arte- plantation, due to aggressive immu- option for selected patients with rial procedures.893 Significantly more nosuppression. Transplant recipi- end-stage cardiac disease. In 2007, SSIs occurred in the single-dose ents with infections are commonly the United Network for Organ Shar- group (28 [18%] of 153 patients) asymptomatic or have nonspecific ing (UNOS) reported that 2209 heart compared with the multidose group symptoms or sequelae of infection, transplants were performed in the (15 [10%] of 149 patients) (relative which makes detection and diagnosis United States, including 327 in chil- risk, 2; 95% CI, –1.02 to 3.92; p = of infections difficult.855,857,894 Postop- dren (<18 years of age).898 The mean 0.041). Ticarcillin–clavulanate has a erative infections caused by bacterial, graft survival rate 10 years after heart short duration of action and is not viral, and fungal pathogens, includ- transplantation is approximately recommended as a routine agent for ing SSIs, UTIs, bloodstream infec- 49%. Infection continues to be an antimicrobial prophylaxis. Practice tions, and pneumonia, are of greater important cause of morbidity and guidelines recommend single-dose concern within the first month after mortality after heart transplantation prophylaxis in vascular procedures transplantation.895-897 Opportunistic and is a primary cause of death in ap- or a maximum duration of therapy infections that result from immu- proximately 14% of patients within of 24 hours postoperatively, re- nosuppression typically occur after the first year after transplantation.899 gardless of the presence of invasive the first month of transplantation. Despite the large number of heart drains.6,41 It is routine for transplant recipients transplantation procedures per- Recommendations. The recom- to receive antimicrobial prophy- formed, few studies have specifically mended regimen for patients under- laxis to prevent opportunistic infec- examined postoperative SSI rates in going vascular procedures associated tions.894-897 A discussion of the pro- this population. General cardiotho- with a higher risk of infection, includ- phylactic strategies for prevention of racic procedures have been associat- ing implantation of prosthetic mate- cytomegalovirus (CMV) infection, ed with SSI rates ranging from 9% to rial, is cefazolin (Table 2). (Strength herpes simplex virus infection, pneu- 55% in the absence of antimicrobial of evidence for prophylaxis = A.) mocystis, UTI in kidney transplant prophylaxis.214,900,901 Studies of gener- Clindamycin and vancomycin should recipients, Aspergillus infection in al cardiothoracic procedures, includ- be reserved as alternative agents as lung transplant recipients, and other ing heart transplantation, found SSIs, described in the Common Principles opportunistic infections outside of particularly mediastinitis, in 3–6% of section of these guidelines. If there are the immediate posttransplantation patients who received antimicrobial surveillance data showing that gram- period is beyond the scope of these prophylaxis.170,902 The frequency was negative organisms are a cause of SSIs guidelines. highest in heart transplant recipients. for the procedure, practitioners may Few well-designed, prospective, The SSI rates reported in patients consider combining clindamycin or comparative studies of antimicrobial undergoing heart transplantation vancomycin with another agent (ce- prophylaxis have been conducted who received antimicrobial pro- fazolin if the patient is not b-lactam with patients undergoing solid-organ phylaxis ranged from 5.8% to 8.8%, allergic; aztreonam, gentamicin, or transplantation, and no formal rec- including mediastinitis in 3–7% of single-dose fluoroquinolone if the ommendations are available from ex- patients.903,904 patient is b-lactam allergic), due to pert consensus panels or professional Several independent risk factors the potential for gastrointestinal flora organizations; however, there are for SSIs after cardiac and thoracic exposure. reviews that provide guidance.8,41,894 procedures have been identified (see The recommendations given for the cardiac and thoracic sections of Heart, lung, and heart–lung each of the solid-organ transplant this article). Heart transplantation transplantation procedures are intended to provide has been identified as an indepen- Background. Solid-organ trans- guidelines for safe and effective dent risk factor for SSIs.170 Other

246 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis independent risk factors for SSIs in the actual perioperative prophy- other cardiac surgical procedures has heart transplantation include age,905 laxis regimen as well as the dura- made it the standard of practice dur- receipt of ciprofloxacin alone for tion of therapy beyond the period ing transplantation.896 prophylaxis,906 positive wire cul- of prophylaxis. No randomized controlled tri- tures,907 a BMI of >30 kg/m2, female Patients requiring ECMO as a als have specifically addressed the sex,908 previous cardiac procedures, bridge to heart transplantation use of antimicrobial prophylaxis in previous left VAD placement, and should be treated with a similar ap- heart transplantation. In an open- hemodynamic instability requiring proach. If there is no history of colo- label noncomparative study, the SSI inotropic support.903,904 Unfavor- nization or previous infection, then rate was 4.5% among 96 patients able functional outcomes were seen the general recommendations for administered cefotaxime plus floxa- in patients who developed infec- SSI antimicrobial prophylaxis for the cillin preoperatively and for 72 hours tions within the first year after heart specific procedure should be followed. after cardiac procedures.912 This rate transplantation associated with lung, In ECMO patients with a history of of infection was similar to that seen bloodstream, and CMV infections.909 colonization or previous infection, in other cardiothoracic, nonheart Independent predictors of mortality changing the preoperative antimicro- transplantation procedures in which in heart transplant recipients includ- bial prophylaxis to cover these patho- antimicrobial prophylaxis was used. ed serum creatinine levels, amyloid gens must be considered, weighing Choice of agent. Antimicrobial etiology, history of hypertension, whether the pathogen is relevant to prophylaxis for heart transplanta- pulmonary infection, and CNS infec- SSIs in the planned procedure. tion should be similar to that used tion. Additional predisposing factors Because heart transplantation is for other types of cardiothoracic for infection in heart transplantation similar to other cardiac and thoracic procedures.911 First- and second- include exposure to pathogens from procedures, similar considerations generation cephalosporins are con- the donor or transplant recipient, the regarding the need for antimicro- sidered to be equally efficacious time from organ recovery to reperfu- bial prophylaxis apply (see the car- and are the preferred agents. There sion, and the immunosuppressive diac and thoracic sections).911 These appear to be no significant differ- regimens used.897,904,910 Similar risk guidelines do not address antimicro- ences in efficacy among prophylac- factors for infection are noted in pe- bial prophylaxis for infective endo- tic regimens using agents such as diatric transplant recipients, with the carditis. Readers are referred to the cefazolin and cefuroxime.914 The use addition of a naive immune system current guidelines for prevention of of antistaphylococcal penicillins, to several pathogens, most notably infective endocarditis from AHA.11,228 either alone or in combination with viruses, as well as incomplete pri- Organisms. As with other types aminoglycosides or cephalosporins, mary immunization series.897 of cardiothoracic procedures, gram- failed to demonstrate superior Patients with an indwelling VAD positive organisms, mainly Staphy- efficacy to that of cephalosporin at the time of heart transplanta- lococcus species, are the primary monotherapy (see the cardiac and tion have additional prophylaxis pathogens that cause SSI after heart thoracic sections) in other cardio- concerns. Recipients who do not transplantation.902,905-907,912,913 MRSA thoracic procedures. have a driveline infection and have was reported in 12–21% of SSIs Several cohort studies examined no history of either colonization or in several cohort studies.903,905,906 antimicrobial prophylactic agents infection should receive prophylaxis Vancomycin-resistant Enterococ- used for patients undergoing heart as described for recipients without a cus faecalis was noted in 15% of transplantation but did not evalu- VAD in place. Patients with a history infections in one cohort study.903 ate efficacy.902,903,905,906 Ciprofloxacin of colonization or previous infection Other gram-positive pathogens alone was found to be an indepen- should have the antimicrobial sensi- (e.g., coagulase-negative staphylo- dent risk factor for incisional SSIs.906 tivities of that organism considered cocci, Enterococcus species)903,905-907,913 Duration. There is no consensus when choosing the SSI prophylactic and gram-negative organisms (e.g., on the optimal duration of antimi- regimen administered, though the Enterobacteriaceae, P. aeruginosa, crobial prophylaxis in cardiotho- duration should still be less than 24 Stenotrophomonas maltophilia) are racic procedures, including heart hours. Heart transplant recipients also a concern for SSIs in heart transplantation. Cohort evalua- with an active VAD driveline infec- transplant recipients, as are Candida tions of patients undergoing heart tion at the time of heart transplan- species.903,906 transplantation reported durations tation should be given appropriate Efficacy. Despite the paucity of lit- of antimicrobial prophylaxis with antimicrobials specifically for the erature on antimicrobial prophylaxis cefazolin or vancomycin of 24 or 48 treatment of that infection. This for the prevention of SSIs in heart hours postoperatively.902,903,905 Data intervention will usually determine transplantation, the efficacy noted in from cardiothoracic procedures

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 247 ASHP Report Antimicrobial prophylaxis also support a range of prophylaxis laxis is indicated for all patients un- 24.8% of lung and 18.3% of heart– durations, from a single dose to 24 dergoing heart transplantation (see lung transplant recipients.899 Among or 48 hours postoperatively.41,131 The cardiac and thoracic sections). The the top 10 primary causes of death currently accepted duration for these recommended regimen is a single within the first year after lung and procedures, which do not include dose of cefazolin (Table 2). There is heart–lung transplantations were transplantation, is 24–48 hours no evidence to support continuing sepsis, pneumonia, fungal infection postoperatively.41,59,131,201 The dura- prophylaxis until chest and medi- (lung only), and CMV infection.899 A tion of antimicrobial prophylaxis for astinal drainage tubes are removed. study of two cohorts of patients un- patients who do not have their chest Alternatives include vancomycin dergoing heart, lung, and heart–lung primarily closed is unclear; most or clindamycin with or without transplantations who received anti- centers continue prophylaxis until gentamicin, aztreonam, or a single microbial prophylaxis evaluated the the chest is closed, but there is no fluoroquinolone dose. (Strength of rate of SSIs and mediastinitis.904,908 evidence to support this practice. evidence for prophylaxis = A.) The The rate of SSI among all transplant Pediatric efficacy. No randomized optimal duration of antimicrobial recipients was 12.98%, with the controlled studies have specifically prophylaxis for patients who do not majority of infections (72%) being addressed antimicrobial prophylaxis have their chest primarily closed organ/space infections, followed by for heart transplantation in pediatric is unclear. No recommendation is deep incisional infections (17%) patients. Infants are at risk for me- made for these patients. Patients who and superficial incisional infections diastinitis caused by gram-negative have left VADs as a bridge and who (10%).908 The overall rate of medias- as well as gram-positive organisms. are chronically infected might also tinitis in a similar cohort was 2.7%, Pediatric patients undergoing heart benefit from coverage of the infecting with rates of 5.2% in heart–lung transplantation should be treated microorganism. transplant recipients and 3.2% in according to recommendations for Lung and heart–lung transplanta- bilateral lung transplant recipients.904 other types of cardiothoracic proce- tion. Background. Lung transplan- Pneumonia was reported in 26.4% of dures. The recommended regimen for tation is an accepted option for a transplantation patients overall, with pediatric patients undergoing cardio- variety of end-stage, irreversible lung rates of 20.7% in lung transplant thoracic procedures is cefazolin 25–50 diseases. The most common diseases recipients and 40% in heart–lung mg/kg i.v. within 60 minutes before for which lung transplantation is transplant recipients.908 A cohort of surgical incision and every 8 hours for performed are idiopathic pulmonary lung transplant recipients reported up to 48 hours. Cefuroxime 50 mg/kg fibrosis, chronic obstructive pul- a rate of 2.2 episodes of pneumonia i.v. within 60 minutes before surgical monary disease, emphysema, cystic per patient during a median follow- incision and every 8 hours for up to 48 fibrosis, a-1-antitrypsin deficiency, up period of 412 days (range, 1–1328 hours is an acceptable alternative. Van- and idiopathic pulmonary arterial days).920 comycin 10–20 mg/kg i.v. over 60–120 hypertension.915,916 UNOS reported Bronchial anastomotic infections, minutes, with or without gentamicin that in the United States in 2007, especially fungal infections, can be 2 mg/kg i.v., should be reserved as an 1468 lung transplantations and 31 serious and are potentially fatal in alternative on the basis of guidelines heart–lung transplantations were lung transplant recipients.921,922 The from HICPAC for routine antimicro- conducted in adults, and 52 lung lung allocation score (LAS) is a rat- bial prophylaxis in institutions that transplantations and 3 heart–lung ing system adopted by the Organ have a high prevalence of MRSA, transplantations were performed Procurement and Transplant Net- for patients who are colonized with in children.898,917 Ten-year survival work and UNOS in 2005 to improve MRSA, or for patients with a true rates were reported as 29.7% of organ allocation and transplantation b-lactam allergy.8 Additional doses double-lung, 17.5% of single-lung, outcomes. The LAS is based on the may be needed intraoperatively for and 25.8% of heart–lung transplant risk of death while on the waiting list procedures >4 hours in duration, for recipients.899 The reported three-year for transplantation and the expected patients with major blood loss, or for survival rate for pediatric lung trans- 1-year survival after transplantation. extended use of CPB depending on plant recipients was 57%.897 Patients with a low LAS are unlikely the half-life of the prophylactic anti- Infections are the most common to undergo transplantation. A study microbial. Fluoroquinolones are not complications after lung and heart– of lung transplant recipients age 12 routinely recommended in pediatric lung transplantations.899,915,918,919 In an years or older revealed a higher rate patients. analysis of UNOS data over an 18- of infection and other morbidities Recommendations. Based on data year period, infection was the num- and a lower 1-year survival rate in for other types of cardiothoracic ber one cause of death within the first patients with a high LAS at the time procedures, antimicrobial prophy- year of transplantation, occurring in of transplantation than in patients

248 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis with a low LAS at the time of trans- in mediastinitis and pneumonia in complications associated with lung plantation.923 Thus, the potential for patients undergoing lung transplan- transplantation, no randomized con- bronchial anastomotic infection and tation.894,904,908 The most frequent trolled trials regarding antimicrobial a poor posttransplantation outcome organisms found in SSIs or medi- prophylaxis for lung or heart–lung needs to be considered in patients astinitis in two cohort studies were transplantation have been published; undergoing lung transplantation. P. aeruginosa,904,908 Candida species, however, antimicrobial prophylaxis Among lung transplantation pa- S. aureus (including MRSA),908 is considered standard practice in tients, risk factors for nosocomial enterococci, coagulase-negative these patients.896 Antimicrobial pro- infections included a-1-antitrypsin staphylococci (e.g., S. epidermidis), phylaxis is routinely administered to deficiency and repeat transplanta- Burkholderia cepacia,904 E. coli, and patients undergoing lung or heart– tion. Risk factors for pneumonia Klebsiella species. lung transplantation, with the aim included colonized or infected do- Patients undergoing lung trans- of preventing pneumonia as well as nor bronchus and perfusate and plantation are also at risk for bacte- SSIs. The rate of pneumonia within preoperative colonization with gram- rial or fungal pneumonia due to the first two weeks postoperatively negative rods. Risk factors for mor- colonization or infection of the lower has reportedly been decreased from tality among the transplant recipi- and upper airways of the donor, 35% to approximately 10% by rou- ents were cystic fibrosis, nosocomial recipient, or both.915 Organisms re- tine antimicrobial prophylaxis.927-929 infection, and ventilation before ported to cause pneumonia in lung Improvements in surgical technique transplantation.908 Risk factors for transplantation patients include and postoperative patient care are mediastinitis after heart, lung, and P. aeruginosa,894,896,904,908,920 S. aureus also important factors in the appar- heart–lung transplantation were (including MRSA),894,896,904,908 B. cepa- ently lower rates of pneumonia after degree of immunosuppression, im- cia,896,904,908 Enterobacter species,908 lung transplantation. paired renal function, previous S. maltophilia, Klebsiella species,904,908 Choice of agent. No formal stud- sternotomy, and reexploration due S. epidermidis,904 E. coli, Aspergillus ies have addressed optimal pro- to bleeding.904 There was a positive species,920 and VRE.894 Similarly, or- phylaxis for patients undergoing association between pretransplan- ganisms frequently seen in pediatric lung transplantation. Antimicrobial tation colonizing microorganisms lung infections are nonfermenting prophylaxis for lung and heart–lung from suppurative lung disease pa- gram-negative bacteria, such as Pseu- transplantation should generally be tients and pneumonia after trans- domonas species, Stenotrophomonas similar to that used for other cardio- plantation.920 Transplantation alters species, Alcaligenes species, and thoracic procedures (see the cardiac the physiological function of lungs, fungi, including Aspergillus species.897 and thoracic sections). First- and including the impairment of muco- The donor lung appears to be second-generation cephalosporins ciliary clearance and interruption of a major route of transmission of are considered equally efficacious and the cough reflex, leading to a higher pathogens; 75–90% of bronchial are the preferred agents for these pro- risk of pulmonary infections.896 washings from donor organs are cedures. However, prophylactic regi- In patients requiring ECMO as a positive for at least one bacterial mens should be modified to include bridge to lung transplantation who organism.920,924,925 Organ recipients coverage for any potential bacterial have no history of colonization or may also be the source of infection pathogens, including gram-negative previous infection, the general rec- of the transplanted organ. This is and fungal organisms, that have been ommendations for SSI antimicro- particularly true in patients with isolated from the recipient’s airways bial prophylaxis for the procedure cystic fibrosis because of the frequent or the donor lung through preopera- should be followed. In ECMO pa- presence of P. aeruginosa in the upper tive cultures.894,896,904,908,915,920 Patients tients with a history of colonization airways and sinuses before trans- with end-stage cystic fibrosis should or previous infection, changing the plantation.896,919 These pathogens are receive antimicrobials on the basis preoperative antimicrobial prophy- often multidrug resistant, likely due, of the known susceptibilities of laxis to cover these pathogens must in large part, to frequent administra- pretransplant isolates, particularly be considered, weighing whether the tion of broad-spectrum antimicro- P. aeruginosa, B. cepacia complex, pathogen is relevant to SSIs in the bials during the course of the dis- and Aspergillus species. planned procedure. ease. Multidrug-resistant strains of Antimicrobial prophylaxis regi- Organisms. While gram-positive B. cepacia and S. maltophilia may be mens reported in cohort evalua- and gram-negative organisms are a problem in cystic fibrosis patients tions of thoracic transplantation, of concern in heart transplantation, in some transplantation centers.919,926 including lungs, have varied.904,908,920 there is increased concern regarding Efficacy. Although much has been One study used ceftazidime, floxa- gram-negative and fungal pathogens published about general infectious cillin, tobramycin, and itraconazole

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 249 ASHP Report Antimicrobial prophylaxis in these patients.908 In addition, all Treatment may include additional tion is a lifesaving procedure for patients received nebulized am- antibacterial agents or antifungal many patients with end-stage hepatic photericin B and oral itraconazole agents. disease for whom there are no other as antifungal prophylaxis. Another Recommendations. Based on data medical or surgical options.932,933 In cohort study used cefepime for lung from other types of cardiothoracic 2007, UNOS reported that 6494 liver transplant recipients without known procedures, all adult patients under- transplantations were performed in colonization; for those with known going lung transplantation should the United States, 96% of which had a colonization, the selection of agents receive antimicrobial prophylaxis, cadaveric donor and 4% had a living- was based on organism susceptibil- because of the high risk of infection. related donor source.934 These liver ity.920 A third cohort reported use Patients with negative pretransplan- transplantations were performed in of metronidazole and aztreonam as tation cultures should receive anti- 5889 adults and 605 pediatric (<18 prophylaxis for patients with a septic microbial prophylaxis as appropriate years old) patients. Reported 1-year lung (positive sputum culture).904 for other types of cardiothoracic patient survival rates for adults Antifungal prophylaxis should procedures. ranged from 76.9% to 95%932,935-938 be considered, especially when pre- The recommended regimen is a and from 80% to 91.7% for pediatric transplantation cultures reveal fungi single dose of cefazolin (Table 2). patients.934,939-942 Survival at 3 and 5 in the donor lung915 or the recipient’s There is no evidence to support years ranged from 68.5% to 80.9%934 airway. There is no consensus on continuing prophylaxis until chest and from 61.6% to 76.5%932,933 in the appropriate antifungal agent for and mediastinal drainage tubes are adult patients, respectively. In pedi- lung transplant recipients.894,896,930 removed. Alternatives include van- atric patients, 3- and 5-year survival Selection is recommended based on comycin with or without gentamicin, ranged from 73.2% to 86%897,934,941 patient risk factors for infection (e.g., aztreonam, and a single fluoroquino- and from 69.2% to 80.1%,934 re- cystic fibrosis) and colonization, pre- lone dose. (Strength of evidence for spectively. One-year graft survival transplantation and posttransplanta- prophylaxis = A.) The optimal dura- rates ranged from 74.2% to 94% in tion cultures, and local fungus epi- tion of antimicrobial prophylaxis adults934-936,938 and from 72.1% to demiology.894,896,897,930 Because of the for patients who do not have their 86.1% in pediatric patients.934,941,942 serious nature of fungal infections chest primarily closed is unclear. No Graft survival at 3 and 5 years ranged in the early posttransplantation pe- recommendation is made for these from 58.9% to 75.5% and from riod and the availability of antifungal patients. 51.6% to 70.5%, respectively, in agents, prophylaxis should be con- The prophylactic regimen should adults and from 62.5% to 77.6% and sidered when Candida or Aspergillus be modified to provide coverage from 68.4% to 71.4%, respectively, in species are isolated from the donor against any potential pathogens, pediatric patients.934,941 No significant lung915 or recipient’s airway. including gram-negative (e.g., differences were noted in graft or pa- Duration. No well-conducted P. aeruginosa) and fungal organ- tient survival between cadaveric and studies have addressed the optimal isms, isolated from the donor lung living-related donors in adult and pe- duration of antimicrobial prophy- or the recipient pretransplantation. diatric liver transplant recipients.934 laxis for lung or heart–lung trans- The prophylactic regimen may also Infection remains a major cause of plantation. In the absence of posi- include antifungal agents for Candida morbidity and mortality in liver tive cultures from the donor or the and Aspergillus species based on pa- transplant recipients. Infections may recipient, prophylactic regimens of tient risk factors for infection (e.g., occur in 31–83% of patients within 48–72 hours and no longer than 7 cystic fibrosis) and colonization, three months of transplantation days have been reported.896,904,905,931 In pretransplantation and posttrans- and are the cause of death in 4–53% patients with positive pretransplan- plantation cultures, and local fungus of patients.934,936,940,943-950 These rates tation cultures from donor or recipi- epidemiology. Patients undergoing are highly variable and do not seem ent organs or patients with positive lung transplantation for cystic fi- to have changed despite advances cultures after transplantation, post- brosis should receive treatment for in surgical technique and medical operative antimicrobial treatment at least seven days with antimicrobi- management. SSIs within 30 days for 7–14 days or longer has been als selected according to pretrans- after transplantation ranged from reported, particularly for patients plantation culture and susceptibil- 4% to 48% with antimicrobial pro- with cystic fibrosis and previous P. ity results. (Strength of evidence for phylaxis in several cohort and con- aeruginosa and multidrug-resistant prophylaxis = B.) trolled studies.935-938,941,942,948,949,951-964 infections.896,915,919 Such antimicrobial Superficial SSIs are seen most often administration is viewed as treat- Liver transplantation within the first two to three weeks ment and not as surgical prophylaxis. Background. Liver transplanta- postoperatively, whereas organ/space

250 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis infections and deep infections are gens. Infections due to P. aerugi- timicrobial regimens.939,940,943,945 The seen after three to four weeks. nosa may also occur but are much frequency of these infections varies Liver transplantation is often less common in the early postopera- from 10% to 55% despite antimi- considered to be the most techni- tive period.936,937,939,940,942,945,947,948,952,959,969 crobial prophylaxis.939,940,943,945,979 It is cally difficult of the solid-organ Enterococci are particularly common difficult to assess the efficacy of pro- transplantation procedures. Surgi- pathogens and may be responsible phylactic regimens in reducing the cal procedures lasting longer than for 20–46% of SSIs and intraabdom- rate of infection, because prophylaxis 8–12 hours have been consistently inal infections.894,933,935,937,938,940,943, has been routinely used in light of the identified as one of the most impor- 945-947,951,952,955,964,965,969 S. aureus (fre- complexity of the surgical procedure; tant risk factors for early infectious quently MRSA) and coagulase- therefore, reliable rates of infection complications, including SSIs, in- negative staphylococci are also in the absence of prophylaxis are traabdominal infections, and biliary common causes of postopera- not available. No controlled studies tract infections.896,938,939,945,947,957 Other tive SSIs.936-938,940,942,943,945-949,955,957- have compared prophylaxis with no important risk factors for infectious 961,964,965,970,971 Candida species com- prophylaxis. complications related to liver trans- monly cause both early and late Choice of agent. Antimicrobi- plantation surgery include previous postoperative infections.933,936,937,940,942, al prophylaxis should be directed hepatobiliary surgery,896,939,945,947,952,963 943,945-947,949,951,969 against the pathogens most com- previous liver or kidney transplanta- Several studies have noted monly isolated from early infections tion,937,951,952,965 and surgical compli- increasing concern about antimi- (i.e., gram-negative aerobic ba- cations such as anastomotic leak- crobial resistance based on detection cilli, staphylococci, and enterococci). age.896,938,939,945,947,951,952 Patient-related of resistant organisms, includ- Traditional prophylactic regimens risk factors for infection after liver ing E. coli,935,937 Enterococcus spe- have therefore consisted of a third- transplantation include antimicro- cies,933,937,964,965 Enterobacter species,964 generation cephalosporin (usually bial use within three to four months Klebsiella species,933,937 coagulase- cefotaxime, because of its antistaph- before transplantation,935,954 low negative staphylococci,937,964 and ylococcal activity) plus ampicil- pretransplantation serum albumin S. aureus.937,948,957-961,970 General infor- lin.936,937,943,944,946-948,951,952,954,962,965,967,979 concentration,938,958,963 high pretrans- mation on antimicrobial resistance is The use of cefoxitin and ampicillin– plantation serum bilirubin concen- provided in the Common Principles sulbactam, cefotaxime and ampicil- tration,939,945,947 ascites,938 obesity,963 section of these guidelines. Of spe- lin–sulbactam and gentamicin,957-959 diabetes, and hemochromatosis.966 cific concern to the transplantation cefuroxime and metronidazole,971 Procedure-related risk factors for community is the emergence of ceftriaxone and metronidazole,980 infection include transfusion of >4 multidrug-resistant A. bauman- cefotaxime and metronidazole,953 units of red blood cells,896,951 bacte- nii,972 carbapenem-resistant Entero- ceftriaxone and ampicillin,949 cefti- rial contamination due to entry into bacteriaceae,973,974 K. pneumoniae zoxime alone,955 cefotaxime and the gastrointestinal tract,963 surgi- carbapenemase-producing organ- tobramycin,956 cefoxitin alone,960,961 cal incision method,963 and use of isms,975 and C. difficile.976-978 cefazolin alone,951 amoxicillin– muromonab-CD3 within the first Efficacy. Although there remains a clavulanate and gentamicin,970 week after transplantation.938 high rate of infection directly related amoxicillin–clavulanate alone,951 Organisms. The pathogens most to the liver transplantation proce- glycopeptides and antipseudo- commonly associated with ear- dure, there are few well-controlled monal penicillin,951 quinolone and ly SSIs and intraabdominal in- studies concerning optimal antimi- amoxicillin–clavulanate or gly- fections are those derived from crobial prophylaxis. In evaluating the copeptide,951 vancomycin and the normal flora of the intesti- efficacy of prophylactic regimens, it aztreonam,951,981 and piperacillin– nal lumen and the skin. Aerobic is important to differentiate between tazobactam964,970 has also been re- gram-negative bacilli, including early infections (occurring within ported. Alternative prophylaxis regi- E. coli,935,937,939,940,942,945,947-949,951,967,968 14–30 days after surgery) and late mens for b-lactam-allergic patients Klebsiella species,933,936,937,939,940,945, infections (occurring more than 30 have included cefuroxime and met- 947-949,967-969 Enterobacter species,936,939, days after surgery). Infections occur- ronidazole,970 clindamycin and gen- 940,942,945,947,952,959,964,967,968 Acinetobacter ring in the early postoperative period tamicin or aztreonam,948,960-962 cipro- baumannii,935-937,942,951 and Citrobac- are most commonly associated with floxacin and metronidazole,970 and ter species,939,940,945,947,952,959,967,968 are biliary, vascular, and abdominal sur- vancomycin or ciprofloxacin.936 Imi- common causes of SSIs and intraab- geries involved in the transplantation penem alone was used in one study dominal infections and account for procedure itself and are thus most for patients with renal failure.956 The up to 65% of all bacterial patho- preventable with prophylactic an- efficacy of these regimens compared

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 251 ASHP Report Antimicrobial prophylaxis with cefotaxime plus ampicillin is Universal antifungal prophylaxis is recent studies have limited the dura- difficult to assess due to different probably not necessary, since the tion of prophylaxis to 72 hours,981 48 definitions of infection used in the risk of invasive candidiasis is low hours,936,943,945,952,955,956,960,961,967,970,979,980,991 available studies and variability of in uncomplicated cases. Instead, 36 hours,981 24 hours,935,948,962,970 and study design (many single-center prophylaxis is generally reserved for a single dose,963 with no apparent cohort studies) in different countries. patients with two or more of the fol- differences in early infection rates. A One prospective nonrandomized lowing risk factors: need for reopera- prospective, nonrandomized, con- study found no difference in the tion, retransplantation, renal failure, trolled study found no difference in frequency of SSIs in orthotopic liver choledochojejunostomy, and known bacterial infections within the first transplant recipients with cefazolin colonization with Candida species.15 three months after liver transplanta- alone and amoxicillin–clavulanate Risk is also increased with prolonged tion in patients receiving cefotaxime alone, both given one hour before initial procedure or transfusion of and ampicillin as short-term an- surgical incision, with a second dose >40 units of cellular blood products, timicrobial prophylaxis for two to given in cases of significant bleeding but this cannot be predicted before three days, compared with long-term or surgery lasting over six hours, as the procedure. prophylaxis for five to seven days.954 antimicrobial prophylaxis.935 The Selective bowel decontamina- Of note, 5 of the 11 patients in the study did find a significantly higher tion to eliminate aerobic gram- long-term prophylaxis group had rate of A. baumannii in the cefazo- negative bacilli and yeast from detectable C. difficile toxin B in the lin group than the amoxicillin– the bowel before the transplanta- feces and developed enteritis. No clavulanate group. The routine use of tion procedure has been evaluated patients in the short-term group had vancomycin as antimicrobial prophy- in several studies and a meta- detectable C. difficile. Two recent re- laxis is not recommended because of analysis.936,943,949,955,956,967,968,980,990,991 view articles noted that antimicrobial the risk of developing vancomycin- These studies used combinations of prophylaxis duration should be less resistant organisms,8,950 but vancomy- nonabsorbable antibacterials (ami- than three days.896,950 cin may be reserved for centers with noglycosides, polymyxin B or E), Pediatric efficacy. There are few an MRSA or MRSE cluster.8,950,957-959 antifungals (nystatin, amphotericin data specifically concerning antimi- No randomized controlled studies B), and other antimicrobials (cefu- crobial prophylaxis in liver trans- have been conducted to compare roxime in suspension) administered plantation in pediatric patients. The the efficacy of other antimicrobial orally and applied to the oropha- combination of cefotaxime plus prophylactic regimens in the preven- ryngeal cavity in combination with ampicillin has been reportedly used tion of early postoperative infections. systemically administered antimicro- in children undergoing living-related For patients known to be colonized bials. Results are conflicting, with no donor liver transplantation; the ef- with MRSA, VRE, or resistant gram- differences in patient outcomes (e.g., ficacy of this regimen appeared to negative pathogens, it is reasonable infection rates, mortality) or cost and be favorable.946 A small, retrospec- to consider prophylaxis specifically concerns of increasing gram-positive tive, single-center cohort study targeted at these organisms. See the infections with potential resistance reported outcomes of children un- Common Principles section for fur- in several studies939,955,956,980,991 and dergoing liver, heart, small bowel, or ther discussion. others with positive results.936,949 Two lung transplantation receiving Postoperative infections with randomized controlled studies found piperacillin–tazobactam 120–150 Candida species after liver trans- significantly fewer bacterial infec- mg/kg/day beginning before surgical plantation are common, particularly tions with early enteral nutrition incision and continuing for 48 hours in the abdomen, and are frequently plus lactobacillus and fibers.971,980 postoperatively and found favorable considered organ/space SSIs. For this Based on currently available data, the results, with a superficial SSI rate of reason, the use of antifungal prophy- routine use of selective bowel decon- 8% and no deep SSIs.992 laxis in the perioperative period has tamination or lactic acid bacteria and Recommendations. The recom- become common. Efficacy has been fibers in patients undergoing liver mended agents for patients under- demonstrated for fluconazole,964-984 transplantation is not recommended. going liver transplantation are (1) lipid complex amphotericin B,985-987 Duration. No studies have as- piperacillin–tazobactam and (2) and caspofungin.988 Finally, one sessed the optimal duration of cefotaxime plus ampicillin (Table meta-analysis found a decreased risk antimicrobial prophylaxis in liver 2). (Strength of evidence for proof fungal infection and death associ- transplantation. Although antimi- phylaxis = B.) For patients who are ated with fungal infection, though crobials have been administered in allergic to b-lactam antimicrobials, not overall mortality, among pa- studies for five days937,944,946,949,957-959 clindamycin or vancomycin given tients given antifungal prophylaxis.989 and seven days,964 the majority of in combination with gentamicin,

252 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis aztreonam, or a fluoroquinolone is a the first 30 days to three months af- ducted, several open-label, noncom- reasonable alternative. The duration ter transplantation.1000-1002,1005,1008,1009 parative, single-center studies have of prophylaxis should be restricted to UTIs are also a significant concern suggested that antimicrobial pro- 24 hours or less. For patients at high during the same time frame, with phylaxis substantially decreases the risk of Candida infection, flucon- rates ranging from 10.6% to 49% in rate of superficial and deep SSIs after azole adjusted for renal function may pancreas transplant recipients who pancreas or SPK transplantation. SSI be considered. (Strength of evidence received antimicrobial prophylaxis, rates were 7–33% with various pro- for prophylaxis = B.) and are much more common in re- phylactic regimens,995,1000-1002,1004,1005 cipients with bladder drainage com- compared with 7–50% for historical Pancreas and pancreas–kidney pared with enteric drainage.1000-1008 controls in the absence of prophy- transplantation Pancreas and SPK transplantation laxis.1009,1010 The reason for the wide Background. Pancreas transplan- patients may be at increased risk of disparity in infection rates observed tation is an accepted therapeutic SSIs and other infections because of with prophylaxis is not readily ap- intervention for type 1 diabetes the combined immunosuppressive parent but may include variations mellitus; it is the only therapy that effects of diabetes mellitus and the in SSI definitions, variations in anti- consistently achieves euglycemia immunosuppressive drugs used to microbial prophylaxis, immunosup- without dependence on exogenous prevent graft rejection.995,1000 Other pression protocols, and variations in insulin.993-997 Simultaneous pancreas– factors associated with increased surgical techniques.999-1002,1005,1007,1008 kidney (SPK) transplantation is an SSI rates include prolonged operat- Choice of agent. Because of the accepted procedure for patients with ing and ischemic times (>4 hours), broad range of potential pathogens, type 1 diabetes and severe diabetic organ donor age of >55 years, and several studies have used multidrug nephropathy. In 2007, UNOS re- enteric rather than bladder drainage prophylactic regimens, including ported that 469 pancreas transplan- of pancreatic duct secretions.895,995,1000 imipenem–cilastatin plus vanco- tations and 862 SPK transplantations Prolonged organ preservation time mycin995; tobramycin, vancomycin, were performed in the United States, (>20 hours) was shown to increase and fluconazole1010; cefotaxime, of which 60 and 4 patients, respec- the risk of complications, includ- metronidazole, and vancomycin1012; tively, were under age 18 years.998 ing duodenal leaks and decreased cefotaxime, vancomycin, and fluco- Pancreas graft 1-year survival rates graft survival in cadaveric pancreas nazole1008; ampicillin and cefotaxi- ranged from 70.2% to 89%, and the transplant recipients.1003 Risk factors me1007; and piperacillin–tazobactam 3-year rates ranged from 48% to for UTI are reviewed in the kidney and fluconazole.1006 85.8%.998-1002 Patient survival with transplant section. HICPAC recommendations for pancreas transplantation has been Organisms. A majority of su- SSI prevention include limiting the reported between 75% and 97% at 1 perficial SSIs after pancreas or SPK use of vancomycin unless there is year and between 54% and 92.5% at transplantation are caused by Staph- an MRSA or MRSE cluster or as 3 years.998 Allograft survival is higher ylococcus species (both coagulase- an alternative for b-lactam-allergic in recipients of SPK transplanta- positive and coagulase-negative) patients, though transplantation tions, with allograft survival rates of and gram-negative bacilli (par- procedures were not specifically cov- 86.1–95.1% at 1 year and 54.2–92.5% ticularly E. coli and Klebsiella spe- ered in the guidelines.8 Limited data at 3 years. Reported patient survival cies).993-997,1000-1002,1004-1006,1009-1011 Deep are available on the use of vanco- rates in SPK are 91.7–97.6% at 1 year SSIs also are frequently associ- mycin as antimicrobial prophylaxis and 84.4–94.1% at 3 years. During ated with gram-positive (Enterococ- in kidney or pancreas transplanta- pancreas transplantation, surgical cus species, Streptococcus species, tion, or both. A small, randomized, complications with portal-hepatic and Peptostreptococcus species) and active-controlled, single-center study drainage significantly decreased the gram-negative organisms (Entero- evaluated the impact of vancomycin- 1-year and 3-year survival rates to bacter species, Morganella species, containing antimicrobial prophylaxis 48% and 44%, respectively, in one and B. fragilis), as well as Candida regimens in kidney and pancreas cohort study.999 species.993-997,1000-1002,1004-1006,1009-1011 Al- (alone or SPK) transplant recipients Infectious complications are a though anaerobes are occasion- on the frequency of gram-positive major source of morbidity and ally isolated, the necessity for specific infections.1004 Renal transplantation mortality in patients undergoing treatment of anaerobes in SSIs after patients received either vancomycin pancreas or SPK transplantation; the pancreas transplantation remains and ceftriaxone or cefazolin, and frequency of SSI is 7–50% with an- unclear. pancreas transplantation patients timicrobial prophylaxis.993-997,1000-1009 Efficacy. Although no placebo- received either vancomycin and gen- The majority of SSIs occurred within controlled studies have been con- tamicin or cefazolin and gentamicin.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 253 ASHP Report Antimicrobial prophylaxis

There was no statistically significant as a risk factor for postoperative United States; of these, 796 patients difference in the risk of developing fungal infections, many institutions were younger than 18 years.998 The gram-positive infections between use fluconazole for prophylaxis with rate of postoperative infection after antimicrobial prophylaxis regimens bladder-drained organs as well. In this procedure has been reported to with and without vancomycin. The settings with a high prevalence of range from 10% to 56%, with the study was not powered to detect a non-albicans Candida species, a two most common infections be- difference in efficacy between the lipid-based formulation of ampho- ing UTIs and SSIs.1004,1014-1024 Graft antimicrobial regimens. For patients tericin B has been recommended in loss due to infection occurs in up known to be colonized with MRSA, infectious diseases guidelines from to 33% of cases.1017,1023 One study of VRE, or resistant gram-negative the American Society of Transplan- adult and pediatric kidney trans- pathogens, it is reasonable to con- tation and the American Society of plant recipients (both living-related sider prophylaxis targeted specifically Transplant Surgeons.15 and cadaveric donor sources) found for these organisms. See the Com- Duration. Studies evaluating the patient survival rates at 7 years after mon Principles section for further use of antimicrobial prophylaxis regi- transplantation of 88.9% and 75.5%, discussion. mens in pancreas and SPK transplan- respectively, and graft survival of An evaluation of the surgical com- tation, summarized above, ranged 75% and 55.5%, respectively.1025 No plications of pancreas transplant re- from a single preoperative dose of patients developed an SSI. Mortality cipients with portal-enteric drainage cefazolin to multidrug regimens of associated with postoperative infec- found an intraabdominal infection 2–5 days’ duration.995,1005,1009,1010,1012 tions is substantial and ranges from rate of 12% in the 65 patients under- More recent studies reported mono- approximately 5% to 30%.1015,1017,1019, going SPK transplantation and no therapy regimens with cefazolin 1022,1026,1027 cases in those undergoing pancreas or vancomycin,999 amoxicillin– The frequency of SSIs in kidney transplantation alone.999 All patients clavulanate,1001,1002 and piperacillin– transplant recipients has ranged received either cefazolin 1 g i.v. every tazobactam1000-1002 1–7 days in dura- from 0% to 11% with antimicro- eight hours for one to three days, tion, with the majority using the bial prophylaxis1023-1025,1028,1029 to 2% or vancomycin if the patient had a regimen 48–72 hours after transplan- to 7.5% without systemic prophy- b-lactam allergy. tation. The duration of fluconazole laxis.1030,1031 The majority of these One study evaluated SSI rates in ranged from 7 to 28 days.1002 infections were superficial in nature SPK transplantation after single- Recommendations. The recom- and were detected within 30 days agent, single-dose prophylaxis with mended regimen for patients under- after transplantation.1023,1028-1030 Risk cefazolin 1 g i.v. to donors and re- going pancreas or SPK transplanta- factors for SSI after kidney trans- cipients, as well as cefazolin 1-g/L tion is cefazolin (Table 2). (Strength plantation include contamination of bladder and intraabdominal irriga- of evidence for prophylaxis = A.) For organ perfusate1027; pretransplantation in the recipient.1009 Superficial patients who are allergic to b-lactam tion patient-specific factors, such as SSIs developed in 2 patients (5%), antimicrobials, clindamycin or van- diabetes,1029,1030 chronic glomerulo- and deep SSIs associated with blad- comycin given in combination with nephritis,1030 and obesity1027,1030,1032; der anastomotic leaks or transplant gentamicin, aztreonam, or a fluoro- procedure-related factors, such as pancreatitis occurred in 4 additional quinolone is a reasonable alternative. ureteral leakage and hematoma patients (11%). This study reported The duration of prophylaxis should formation1027; immunosuppressive similar SSI rates as with multidrug, be restricted to 24 hours or less. The therapy1024,1027,1029; and postoperative multidose regimens. use of aminoglycosides in combina- complications, such as acute graft Based on the regularity of isola- tion with other nephrotoxic drugs rejection, reoperation, and delayed tion of Candida species from SSIs may result in renal dysfunction and graft function.1030 In one study, the after pancreas transplantation and should be avoided unless alterna- frequency of SSI was 12% in pa- the frequent colonization of the tives are contraindicated. (Strength tients receiving immunosuppression duodenum with yeast, fluconazole of evidence for prophylaxis = C.) with azathioprine plus prednisone is commonly added to prophylactic For patients at high risk of Candida but only 1.7% in patients receiving regimens. Although never studied infection, fluconazole adjusted for cyclosporine plus prednisone.1033 in a randomized trial, a lower fungal renal function may be considered. A significant difference in SSI rates infection rate was found in one large was noted after kidney transplanta- case series with the use of fluconazole Kidney transplantation tion between immunosuppression (6%) compared with no prophylaxis Background. In 2007, UNOS regimens including mycophenolate (10%).1013 Although enteric drainage reported that 16,628 kidney trans- mofetil (45 [3.9%] of 1150 patients) of the pancreas has been identified plantations were performed in the versus sirolimus (11 [7.4%] of 144

254 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis patients).1029 Sirolimus-containing ney transplantation. These have bial prophylaxis were not statistically immunosuppression was found to included at least one randomized different.1024 be an independent risk factor for controlled trial1014 and many pro- Choice of agent. The available SSIs. These recommendations refer spective and retrospective studies data do not indicate a significant to kidney transplant recipients; comparing infection rates with difference between single-drug recommendations for living kidney prophylaxis and historical infection and multidrug antimicrobial regi- donors can be found in the discus- rates at specific transplantation cen- mens.1014,1018,1021 In addition, there sion of nephrectomy in the urologic ters.1015-1018,1021,1033-1035 Based on the appears to be no significant differ- section. available literature, the routine use ences between single-agent regi- Organisms. Postoperative SSIs of systemic antimicrobial prophy- mens employing antistaphylococ- in kidney transplant recipients are laxis is justified in patients undergo- cal penicillins and first-, second-, caused by gram-positive organisms, ing kidney transplantation. or third-generation cephalospo- particularly Staphylococcus species Two studies that evaluated a rins.1016,1017,1033-1035,1037 Studies have (including S. aureus and S. epider- triple-drug regimen consisting of an directly compared antimicrobial midis) and Enterococcus species, aminoglycoside, an antistaphylococ- regimens in a prospective, controlled gram-negative organisms, E. coli, En- cal penicillin, and ampicillin found fashion. Single-agent prophylaxis terobacter species, Klebsiella species, infection rates of <2%, compared with both cefazolin and ceftriaxone P. aeruginosa, and yeast with Candida with 10–25% with no antimicrobial has been reported to result in SSI species.1004,1014-1021,1023,1024,1026,1028,1030,1034 prophylaxis.1018,1019 More specifically, rates of 0%.1016,1024,1037 One study site in Brazil reported infection rates in patients without A survey of 101 kidney transplant a high level of antimicrobial resis- antimicrobial prophylaxis (45 cadav- centers in 39 countries reported tance.1030 Organisms recovered from eric and 44 living-related donors) that 65% of the centers used single infections included MRSA (77%), were 10.1% in total (8.9% and 11.4%, antimicrobial prophylaxis regimens, methicillin-resistant coagulase- respectively), compared with 1.5% in 20.8% used two-drug regimens, and negative Staphylococcus (53.5%), total (1.5% and 0%, respectively) 3% used three drugs; no prophy- extended-spectrum b-lactamase- with antimicrobial prophylaxis.1018 laxis was used in 11% of centers.1036 producing K. pneumoniae (80%), Infection rates were as high as 33% Cephalosporins were used in 68 cen- and carbapenem-resistant P. aeru- in living-related patients with no ters (55 alone, 7 in combination with ginosa (33.3%). Another center in antimicrobial prophylaxis and 0–1% penicillin, and 6 with other antimi- Brazil reported a significant differ- in both cadaveric and living-related crobials). Penicillins were used by 28 ence in resistance to broad-spectrum transplant recipients with antimicro- centers (13 alone, 7 with cephalospo- antimicrobials in pathogens isolated bial prophylaxis.1021 Piperacillin plus rin, and 8 with other antimicrobials). in UTIs from cadaveric kidney trans- cefuroxime was also shown to be ef- Other antimicrobials (specifics were plant recipients (n = 21, 19.1%) ficacious; infection rates were 3.7%, not reported) were used in 2 centers compared with living-related donor compared with 19% in cadaveric as the single agent. kidney transplant recipients (n = 2, transplant recipients not receiving As noted above, HICPAC rec- 3.7%) (p = 0.008).1024 One center in prophylaxis.1018 Several studies have ommendations for SSI prevention the United States reported 94% sus- shown that single-agent prophylaxis include limiting the use of vanco- ceptibility to vancomycin of Entero- with an antistaphylococcal penicil- mycin to situations in which there is coccus species within the first month lin,1029,1034 a first-generation cepha- an MRSA or MRSE cluster or as an after transplantation, while E. coli, losporin,1016,1017,1023,1024,1029 a second- alternative for b-lactam-allergic pa- cultured most commonly more than generation cephalosporin,1028,1035,1036 tients.8 Transplantation procedures six months after transplantation, was or a third-generation cephalospo- were not specifically covered in the 63% resistant to sulfamethoxazole– rin (e.g., cefoperazone, cefotaxime, guidelines. trimethoprim.1023 This resistance ceftriaxone)1024,1029,1033,1037 can reduce Duration. Studies have used vari- may be related to the routine use of postoperative infection rates to ous prophylactic regimens, ranging sulfamethoxazole–trimethoprim in 0–8.4%. All studies included cadav- from a single-drug cephalosporin prophylaxis of Pneumocystis carinii eric transplant recipients, whereas regimen, administered as a single pneumonia and UTI. living-related transplant recipients preoperative dose or for up to 24 Efficacy. A number of studies were also included in select stud- hours postoperatively, to multi- have clearly demonstrated that an- ies.1017,1024,1028,1036 Where compared drug regimens of two to five days’ timicrobial prophylaxis significantly directly, infection rates between duration.981,1004,1014-1018,1021,1023,1024,1028, decreases postoperative infection cadaveric and living-related trans- 1029,1033,1036,1038 Cefazolin for 24 hours rates in patients undergoing kid- plant recipients receiving antimicro- was equivalent to seven days of surgi-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 255 ASHP Report Antimicrobial prophylaxis cal prophylaxis in living-related kid- dures.1041 The primary goal of these found that antimicrobial prophylax- ney transplant donors.1039 There ap- procedures is to restore function to is does not significantly decrease the pear to be no significant differences the affected area, with a secondary risk of infection. These studies have in SSI rates between single-dose, goal of improving appearance. The evaluated head and neck procedures 24-hour, and multidose regimens; scope of procedures ranges from (facial bone fracture, tumor excision therefore, the duration of antimi- simple primary surgical-site closure, and reconstruction, radical neck crobial should be restricted to 24 skin grafts, and skin flaps to compos- dissection, rhinoplasty),1049 flexor hours. ite tissue transplantations. Composite tendon injury repairs,1051 augmen- Pediatric efficacy. Although pe- tissue transplantation for tissue re- tation mammoplasty using peri- diatric patients were included in construction of the knee joint, larynx, areolar submuscular technique,1052 studies demonstrating the efficacy of uterus, abdominal wall, hand, face, carpal tunnel,1069 and breast pro- antimicrobial prophylaxis, there are and penis has been performed in a cedures (reduction mammoplasty, few data specific to pediatric patients. small number of patients.1042,1043 lumpectomy, mastectomy, axillary One cohort of 96 pediatric pa- Most dermatological, breast (re- node dissection).1056,1058,1070,1071 tients who underwent 104 renal duction and reconstructive), clean However, a Cochrane review transplants (63% cadaveric and 37% head and neck, and facial proce- of seven randomized, placebo- living-related donors) ranged in age dures have an associated SSI rate of controlled trials of 1984 patients from six months to 18 years (mean <5%.1044-1053 Oral procedures, such as undergoing breast cancer procedures age, 8.2 ± 5.5 years).1040 Antimicro- wedge excision of lip or ear, flaps on (axillary lymph node dissection and bial prophylaxis included one dose of the nose,1046,1054 and head and neck primary nonreconstructive surgery) cefotaxime 30-mg/kg i.v. bolus at the flaps, have SSI rates of approximately evaluated the effectiveness of preop- start of the procedure and cefotaxime 5–10%.1053,1055-1060 In addition to gen- erative or perioperative antimicro- 90 mg/kg/day in three divided doses eral risk factors as described in the bial prophylaxis (n = 995) compared during the intensive care unit stay, Common Principles section, factors with placebo or no treatment (n = which averaged one to two days. No that increase the risk of postop- 989) in reducing the rate of postop- SSIs were reported. erative infectious complications for erative infections.1072 Pooled study re- Recommendations. The recom- plastic surgery procedures include sults revealed a significant difference mended agent for patients under- implants,1061 skin irradiation before in SSI rates with antimicrobial pro- going kidney transplantation is the procedure, and procedures below phylaxis (80 [8%] of 995), compared cefazolin (Table 2). (Strength of the waist.1062,1063 with 10.5% (104 of 989) for no anti- evidence for prophylaxis = A.) For Organisms. The most com- microbial prophylaxis (relative risk, patients who are allergic to b-lactam mon organisms in SSIs after plas- 0.72; 95% CI, 0.53–0.97). Review antimicrobials, clindamycin or van- tic surgery procedures are S. au- authors concluded that antimicrobial comycin given in combination with reus, 1045,1049,1050,1053,1054,1056,1063-1068 prophylaxis is warranted to decrease gentamicin, aztreonam, or a fluoro- other staphylococci, and streptococ- the risk of SSIs in nonreconstructive quinolone is a reasonable alternative. ci.1045,1054,1064,1066,1067 Procedures involv- breast cancer procedures. The duration of prophylaxis should ing macerated, moist environments Guidelines also support no an- be restricted to 24 hours or less. The (e.g., under a panus or axilla of an timicrobial prophylaxis in patients use of aminoglycosides in combina- obese individual), below the waist, or undergoing clean facial or nasal tion with other nephrotoxic drugs in patients with diabetes are associ- procedures without an implant.7 may result in renal dysfunction and ated with a higher rate of infection For patients undergoing facial or should be avoided unless alterna- with gram-negative organisms such nasal procedures with an implant, tives are contraindicated. (Strength as P. aeruginosa,1068 Serratia marces- antimicrobial prophylaxis should be of evidence for prophylaxis = C.) cens, or Enterobacteriaceae, including considered.7 For patients at high risk of Candida E. coli,1065,1068 Klebsiella species,1068 and A randomized, double-blind, infection, fluconazole adjusted for P. mirabilis.1065 controlled trial of 207 patients evalu- renal function may be considered. Efficacy. The efficacy of antimicro- ated the use of three antimicrobial bial prophylaxis in select plastic sur- prophylaxis regimens in patients un- Plastic surgery and breast gery procedures has been investigated dergoing abdominoplasty proce- procedures in several clinical trials and cohort dures.1066 The reported SSI rates were Background. Plastic surgery en- studies. 13% for patients receiving no antimi- compasses a broad range of pro- Most placebo-controlled and crobial prophylaxis, 4.3% for those cedures focused on reconstructive, retrospective studies for many clean receiving preoperative antimicrobials dermatological, and cosmetic proce- plastic surgery procedures have only, and 8.7% for those receiving

256 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis one preoperative dose and three Duration. Antimicrobial prophy- microbial prophylaxis in the repair days of postoperative antimicrobi- laxis should be limited to the shortest of cleft lip and palate.1074 The occur- als. There was a significantly lower duration possible to prevent SSIs rence of postoperative infections infection rate in the group receiving (even if a drain or a catheter is left in after these procedures is 1.3%.1075 preoperative antimicrobials only place or an implant is inserted), limit No controlled trials have evaluated compared with the placebo group adverse events, and prevent antimi- the use of antimicrobial prophylaxis (p < 0.05). The infection rate was crobial resistance.8,512,1047,1048,1054,1056 in these procedures. slightly but not significantly higher Multiple studies have found no Recommendations. Antimicrobial in patients who received postopera- significant differences in SSI rates prophylaxis is not recommended for tive antimicrobials. after breast surgery with single-dose most clean procedures in patients Choice of agent. There is no con- preoperative cephalosporin com- without additional postoperative sensus on the appropriate antimi- pared with extended-duration regi- infection risk factors as listed in the crobial agent to use for prophylaxis mens that last from one to five days Common Principles section of these in plastic surgery procedures.1055,1073 postoperatively.1048,1054,1056 guidelines and the background dis- Agents with good gram-positive A randomized, single-blind, con- cussion of this section. Although no coverage and, depending on the site trolled trial of 74 patients undergo- studies have demonstrated antimi- of surgery, activity against common ing surgical ablation of head and crobial efficacy in these procedures, gram-negative organisms are rec- neck malignancies with immediate expert opinion recommends that ommended for patients undergoing free-flap reconstruction found no patients with risk factors undergoing clean plastic surgery procedures with significant differences in SSI rate be- clean plastic procedures receive an- risk factors (listed in the Common tween clindamycin 900 mg i.v. every timicrobial prophylaxis. The recom- Principles section and the back- eight hours for 3 doses compared mendation for clean-contaminated ground discussion of this section) with 15 doses.1057 Both groups were procedures, breast cancer proce- or clean-contaminated procedures. given clindamycin 900 mg i.v. imme- dures, and clean procedures with Cefazolin or ampicillin–sulbactam diately preoperatively, in addition to other risk factors is a single dose of is sufficient in most cases, with the postoperative regimens. cefazolin or ampicillin–sulbactam clindamycin and vancomycin as al- In a controlled study, 200 patients (Table 2). (Strength of evidence for ternatives for patients with b-lactam undergoing septorhinoplasty were prophylaxis = C.) Alternative agents allergy. There are no studies assessing randomized to a single preoperative for patients with b-lactam allergy in- the impact of MRSA on patients un- dose of amoxicillin–clavulanate 2.2 clude clindamycin and vancomycin. dergoing plastic surgery procedures g i.v. administered 30 minutes before If there are surveillance data showing or regarding the need to alter pro- surgical incision only (n = 100) or that gram-negative organisms cause phylaxis regimens in patients within combination with postoperative SSIs for the procedure, the prac- out known colonization with MRSA. oral amoxicillin–clavulanate 1000 titioner may consider combining When vancomycin or clindamycin is mg twice daily for seven days.533 There clindamycin or vancomycin with an- used and if a gram-negative organ- was no significant difference in infec- other agent (cefazolin if the patient ism is highly suspected, practitioners tion rates between the group receiving is not b-lactam allergic; aztreonam, should consider adding cefazolin if only a preoperative dose (0%) and gentamicin, or single-dose fluoro- the patient is not b-lactam allergic; the combination group (3%). There quinolone if the patient is b-lactam if the patient is b-lactam allergic, was a higher rate of adverse events allergic). Postoperative duration of the addition of aztreonam, gentami- (nausea, diarrhea, skin rash, and pru- antimicrobial prophylaxis should be cin, or single-dose fluoroquinolone ritus) among the combination group limited to less than 24 hours, regard- should be considered. If the surgical compared with the group receiving less of the presence of indwelling site involves the ear, an antipseu- only a preoperative dose (p = 0.03). catheters or drains. domonal fluoroquinolone may be The study authors recommended the References considered to cover Pseudomonas use of a single preoperative i.v. dose of 1. American Society of Health-System 1045 species. amoxicillin–clavulanate for endonasal Pharmacists. ASHP therapeutic guide- Although oral agents such as septorhinoplasty. lines on antimicrobial prophylaxis in cephalexin, amoxicillin, clindamycin, Pediatric efficacy. Limited data surgery. Am J Health-Syst Pharm. 1999; 56:1839-88. and azithromycin have been recom- on antimicrobial prophylaxis are 2. Dellinger EP, Gross PA, Barrett TL et mended in reviews of antimicrobial available for pediatric patients al. Quality standard for antimicro- prophylaxis in clean dermatological undergoing plastic surgery proce- bial prophylaxis in surgical procedures. Clin Infect Dis. 1994; 18:422-7. surgery, there is no evidence that dures. There is no consensus among 3. Page CP, Bohnen JM, Fletcher JR et al. supports their use.13,1045,1046,1054 surgeons regarding the use of anti- Antimicrobial prophylaxis for surgical

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 257 ASHP Report Antimicrobial prophylaxis

wounds: guidelines for clinical care. 17. Zelenitsky SA, Ariano RE, Harding GK pharynx-colonized methicillin re- Arch Surg. 1993; 128:79-88. et al. Antibiotic pharmacodynamics sistant Staphylococcus aureus: pre- 4. Dotson LR, Witmer DR. Development in surgical prophylaxis: an association liminary study with 10 carrier infants. of ASHP therapeutic guidelines. Am J between intraoperative antibiotic con- Pediatr Int. 2000; 42:67-70. Health-Syst Pharm. 1995; 52:254-5. centrations and efficacy.Antimicrob 30. Liu CC, Hor LI, Wu YH et al. Inves- 5. Anderson DJ, Kaye KS, Classen D et Agents Chemother. 2002; 46:3026-30. tigation and elimination of epidemic al. Strategies to prevent surgical site 18. Rybak MJ, Lomaestro BM, Rotschafer methicillin-resistant Staphylococcus infections in acute care hospitals. Infect JC et al. Vancomycin therapeutic aureus in a neonatal intensive care unit. Control Hosp Epidemiol. 2008; 29(suppl guidelines: a summary of consensus Min Kuo Hsiao Erh Ko I Hsueh Hui Tsa 1):S51-61. recommendations from the Infec- Chih. (Chinese Medical Journal) 1993; 6. Antimicrobial prophylaxis for surgery. tious Diseases Society of America, the 34:285-93. Treat Guidel Med Lett. 2009; 7:47-52. American Society of Health-System 31. Nateghian A, Taylor G, Robinson JL. 7. Scottish Intercollegiate Guidelines Pharmacists, and the Society of Infec- Risk factors for surgical site infections Network. Antibiotic prophylaxis in tious Diseases Pharmacists. Clin Infect following open-heart surgery in a surgery. www.sign.ac.uk/pdf/sign104. Dis. 2009; 49:325-7. Canadian pediatric population. Am J pdf (accessed 2009 Jul 30). 19. Alphonso N, Anagnostopoulos PV, Infect Control. 2004; 32:397-401. 8. Mangram AJ, Horan TC, Pearson ML Scarpace S et al. Perioperative antibi- 32. Bratzler DW, Houck PM, Richards C et al. Guideline for prevention of surgi- otic prophylaxis in paediatric cardiac et al. Use of antimicrobial prophy- cal site infection. Infect Control Hosp surgery. Cardiol Young. 2007; 17:12-25. laxis for major surgery: baseline results Epidemiol. 1999; 20:250-78. 20. Maher KO, VanDerElzen K, Bove EL from the National Surgical Infection 9. American College of Obstetricians and et al. A retrospective review of three Prevention Project. Arch Surg. 2005; Gynecologists. Antibiotic prophylaxis antibiotic prophylaxis regimens for 140:174-82. for gynecologic procedures. ACOG pediatric cardiac surgical patients. Ann 33. National Healthcare Safety Net- practice bulletin no. 104. Obstet Gyne- Thorac Surg. 2002; 74:1195-200. work. Patient safety component col. 2009; 113:1180-9. 21. Kato Y, Shime N, Hashimoto S et al. manual: surgical site infection (SSI) 10. AAP Comittee on Fetus and Newborn, Effects of controlled perioperative an- event. www.cdc.gov/nhsn/PDFs/ ACOG Committee on Obstetric Prac- timicrobial prophylaxis on infectious pscManual/9pscSSIcurrent.pdf tice, eds. Guidelines for perinatal care. outcomes in pediatric cardiac surgery. (accessed 2011 Apr 5). 6th ed. Elk Grove Village, IL: American Crit Care Med. 2007; 35:1763-8. 34. Horan TC, Gayness RP, Martone WJ Academy of Pediatrics and American 22. Haessler D, Reverdy ME, Neidecker J et et al. CDC definitions of nosocomial College of Obstetricians and Gyne- al. Antibiotic prophylaxis with cefazo- surgical site infections, 1992: a modi- cologists; 2008. lin and gentamicin in cardiac surgery fication of CDC definitions of surgical 11. Wilson W, Taubert KA, Gewitz M et al. for children less than ten kilograms. wound infections. Infect Control Hosp Prevention of infective endocarditis: J Cardiothorac Vasc Anesth. 2003; Epidemiol. 1992; 13:606-8. guidelines from the American Heart As- 17:221-5. 35. National Healthcare Safety Network. sociation: a guideline from the Ameri- 23. Vargas MR, Danton MH, Javaid SM et Patient safety component manual: can Heart Association Rheumatic Fever, al. Pharmacokinetics of intravenous key terms. www.cdc.gov/nhsn/PDFs/ Endocarditis, and Kawasaki Disease flucloxacillin and amoxicillin in neona- pscManual/16pscKeyTerms_current. Committee, Council on Cardiovascular tal and infant cardiopulmonary bypass pdf (accessed 2012 Oct 23). Disease in the Young, and the Council surgery. Eur J Cardiothorac Surg. 2004; 36. Horan TC, Andrus M, Dudeck MA. on Clinical Cardiology, Council on 25:256-60. CDC/NHSN surveillance definition of Cardiovascular Surgery and Anes- 24. Milstone AM, Budd A, Shepard JW et health care-associated infection and thesia, and the Quality of Care and al. Role of decolonization in a compre- criteria for specific types of infections Outcomes Research Interdisciplinary hensive strategy to reduce methicillin- in the acute care setting. Am J Infect Working Group. Circulation. 2007; resistant Staphylococcus aureus infec- Control. 2008; 36:309-32. 116:1736-54. tions in the neonatal intensive care 37. Ehrenkranz NJ, Pfaff SJ. Mediastinitis 12. Freiman JA, Chalmers TC, Smith H et unit: an observational cohort study. complicating cardiac operations: evi- al. The importance of beta, the type Infect Control Hosp Epidemiol. 2010; dence of postoperative causation. Rev II error and sample size in the design 31:558-60. Infect Dis. 1991; 13:803-14. and interpretation of the random- 25. Chua AN, Goldstein SL, Bell D et al. 38. Bowater RJ, Stirling SA, Lilford RJ. ized control trial. N Engl J Med. 1978; Topical mupirocin/sodium hypochlor Is antibiotic prophylaxis in surgery a 299:690-4. ite reduces peritonitis and exit-site generally effective intervention? Test- 13. Edmiston CE, Krepel C, Kelly H et al. infection rates in children. Clin J Am ing a generic hypothesis over a set Perioperative antibiotic prophylaxis Soc Nephrol. 2009; 4:1939-43. of meta-analyses. Ann Surg. 2009; in the gastric bypass patient: do we 26. Paglialonga F, Esposito S, Edefonti A et 249:551-6. achieve therapeutic levels? Surgery. al. Catheter-related infections in chil- 39. Englesbe MJ, Dimick JB, Sonnenday 2004; 136:738-47. dren treated with hemodialysis. Pediatr CJ et al. The Michigan Surgical Quality 14. Claforan (cefotaxime sodium) for in- Nephrol. 2004; 19:1324-33. Collaborative: will a statewide quality jection package insert. Bridgewater, NJ: 27. Shiojima T, Ohki Y, Nako Y et al. improvement initiative pay for itself? Sanofi Aventis; 2009 Jul. Immediate control of a methicillin- Ann Surg. 2007; 246:1100-3. 15. Pappas PG, Silveira FP. Candida in resistant Staphylococcus aureus out- 40. Flum DR, Fisher N, Thompson J et al. solid organ transplant recipients. Am break in a neonatal intensive care unit. Washington state’s approach to vari- J Transplant. 2009; 9(suppl 4):S173-9. J Infect Chemother. 2003; 9:243-7. ability in surgical processes/outcomes: 16. Zelenitsky SA, Silverman RE, Duckworth 28. Romance L, Nicolle L, Ross J et al. Surgical Clinical Outcomes Assessment H et al. A prospective, randomized, An outbreak of methicillin-resistant Program (SCOAP). Surgery. 2005; double-blind study of single high dose Staphylococcus aureus in a pediatric 138:821-8. versus multiple standard dose gen- hospital—how it got away and how we 41. Bratzler DW, Houck PM, for the Surgi- tamicin both in combination with caught it. Can J Infect Control. 1991; cal Infection Prevention Guidelines metronidazole for colorectal surgi- 6:11-3. Writers Workgroup. Antimicrobial cal prophylaxis. J Hosp Infect. 2000; 29. Hayakawa T, Hayashidera T, Katsura prophylaxis for surgery: an advisory 46:135-40. S et al. Nasal mupirocin treatment of statement from the national surgical

258 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

infection prevention project. Clin Infect used to improve adherence for antibi- resistant Staphylococcus aureus Dis. 2004; 38:1706-15. otic prophylaxis in patients undergo- (MRSA) infections in the United King- 42. Fry DE. Surgical site infections and the ing noncardiac surgery. Anesth Analg. dom. J Antimicrob Chemother. 2009; Surgical Care Improvement Project 2007; 104:140-6. 63:849-61. (SCIP): evolution of national quality 57. Rosenberg AD, Wambold D, Kraemer 72. Bolon MK, Morlote M, Weber SG et measures. Surg Infect. 2008; 9:579-84. L et al. Ensuring appropriate timing of al. Glycopeptides are no more effective 43. Watson DS. National patient safety antimicrobial prophylaxis. J Bone Joint than β-lactam agents for prevention of goals and implementation. AORN J. Surg Am. 2008; 90:226-32. surgical site infection after cardiac sur- 2009; 90:123-7. 58. Manniën J, Van Kasteren ME, Nagelkerke gery: a meta-analysis. Clin Infect Dis. 44. Myles JL, Shamanski F, Witte D. The NJ et al. Effect of optimized antibiotic 2004; 38:1357-63. Physicians Quality Reporting Initia- prophylaxis on the incidence of surgi- 73. Finkelstein R, Rabino G, Mashiah T tive: measure, development, imple- cal site infection. Infect Control Hosp et al. Vancomycin versus cefazolin mentation and current procedural Epidemiol. 2006; 27:1340-6. prophylaxis for cardiac surgery in terminology coding. Adv Anat Pathol. 59. Gorbach SL, Condon RE, Conte the setting of a high prevalence of 2010; 17:49-52. JE Jr et al. Evaluation of new anti- methicillin-resistant staphylococcal 45. Callcut RA, Breslin TM. Shaping the infective drugs for surgical prophy- infections. J Thorac Cardiovasc Surg. future of surgery: the role of private laxis. Clin Infect Dis. 1992; 15(suppl 2002; 123:326-32. regulation in determining quality stan- 1):S313-38. 74. Bull AL, Worth LJ, Richards MJ. Impact dards. Ann Surg. 2006; 243:304-12. 60. Källman J, Friberg Ö. Antibiotic proof vancomycin surgical prophylaxis 46. Bratzler DW. The Surgical Infection phylaxis in cardiac surgery—general on the development of methicillin- Prevention and Surgical Care Im principles. APMIS. 2007; 115:1012-5. sensitive Staphylococcus aureus surgical provement Projects: promises and 61. Hidron AI, Edwards JR, Patel J et al., site infections: report from Australian pitfalls. Am Surg. 2006; 72:1010-6. for the National Healthcare Safety Net- surveillance data (VICNISS). Ann Surg. 47. DePalma RG. Surgical quality pro- work Team and participating National Epub ahead of print. 2012 Jul 20 (DOI grams in the Veterans Health Admin- Healthcare Safety Network facilities. 10.1097/SLA.0b013e31825fa398). istration. Am Surg. 2006; 72:999-1004. Antimicrobial-resistant pathogens 75. Gorwitz RJ, Kruszon-Moran D, 48. Gómez MI, Acosta-Gnass SI, Mosqueda- associated with healthcare-associated McAllister SK et al. Changes in the Barboza L et al. Reduction in surgical infections: annual summary of data prevalence of nasal colonization with antibiotic prophylaxis expenditure and reported to the National Healthcare Staphylococcus aureus in the United the rate of surgical site infection by Safety Network at the Centers for States, 2001–2004. J Infect Dis. 2008; means of a protocol that controls the Disease Control and Prevention, 2006– 197:1226-34. use of prophylaxis. Infect Control Hosp 2007. Infect Control Hosp Epidemiol. 76. Milstone AM, Carroll KC, Ross T et al. Epidemiol. 2006; 27:1358-65. 2008; 29:996-1011. Community-associated methicillin- 49. Bond CA, Raehl CL. Clinical and 62. Cefotetan package insert. Shaumburg, resistant Staphylococcus aureus strains economic outcomes of pharmacist- IL: Abraxis Pharmaceutical Products; in pediatric intensive care unit. Emerg managed antimicrobial prophylaxis 2007 Jul. Infect Dis. 2010; 16:647-55. in surgical patients. Am J Health-Syst 63. Cefazolin package insert. Shaumburg, 77. Lo WT, Wang CC, Lin WJ et al. Pharm. 2007; 64:1935-42. IL: Abraxis Pharmaceutical Products; Changes in the nasal colonization with 50. Hermsen ED, Smith Shull S, Puumala 2006 Jul. methicillin-resistant Staphylococcus SE et al. Improvement in prescribing 64. Cefoxitin package insert. Shaumburg, aureus in children: 2004–2009. PLoS habits and economic outcomes as- IL: APP Pharmaceuticals, LLC; 2008 One. 2010; 5:e15791. sociated with the introduction of a Feb. 78. Roberts NJ, Douglas RG. Gentamicin standardized approach for surgical an- 65. Sterile vancomycin package insert. use and Pseudomonas and Serratia timicrobial prophylaxis. Infect Control Shaumburg, IL: APP Pharmaceuticals, resistance: effect of a surgical prophy- Hosp Epidemiol. 2008; 29:457-61. LLC; 2008 Apr. laxis regimen. Antimicrob Agents Che- 51. Alerany C, Campany D, Monterde J et 66. Cefuroxime package insert. Shaum- mother. 1978; 13:214-20. al. Impact of local guidelines and an burg, IL: APP Pharmaceuticals; 2008 79. Kriesel D, Savel TG, Silver AL et al. integrated dispensing system on anti- Nov. Surgical antibiotic prophylaxis and biotic prophylaxis quality in a surgical 67. Invanz (ertapenem injection) package Clostridium difficile toxin positivity. centre. J Hosp Infect. 2005; 60:111-7. insert. Whitehouse Station, NJ: Merck; Arch Surg. 1995; 130:989-93. 52. Allerberger F, Gareis R, Jindrák V et al. 2010 Mar. 80. Privitera G, Scarpellini P, Ortisi G et Antibiotic stewardship implementa 68. Gaynes R, Edwards JR. National Noso- al. Prospective study of Clostridium tion in the EU: the way forward. Expert comial Infections Surveillance System: difficile intestinal colonization and Rev Anti Infect Ther. 2009; 7:1175-83. overview of nosocomial infections disease following single-dose antibiotic 53. Voit SB, Todd JK, Nelson B et al. Elec- caused by gram-negative bacilli. Clin prophylaxis surgery. Antimicrob Agents tronic surveillance system for monitor- Infect Dis. 2005; 41:848-54. Chemother. 1991; 35:208-10. ing surgical antimicrobial prophylaxis. 69. Weigelt JA, Lipsky BA, Tabak UP et al. 81. Jobe BA, Grasley A, Deveney KE et Pediatrics. 2005; 116:1317-22. Surgical site infections: causative path al. Clostridium difficile colitis: an in 54. Kritchevsky SB, Braun BI, Bush AJ et ogens and associated outcomes. Am J creasing hospital-acquired illness. Am J al. The effect of a quality improvement Infect Control. 2010; 38:112-20. Surg. 1995; 169:480-3. collaborative to improve antimicrobial 70. Centers for Disease Control and 82. Morris JG, Shay DK, Hebden JN. En- prophylaxis in surgical patients: a ran- Prevention. Recommendations for terococci resistant to multiple antimi- domized trial. Ann Intern Med. 2008; preventing the spread of vancomycin crobial agents, including vancomycin: 149:472-80. resistance. Recommendations of the establishment of endemicity in a uni- 55. Potenza B, Deligencia M, Estigoy B et Hospital Infection Control Prac- versity medical center. Ann Intern Med. al. Lessons learned from the institu- tices Advisory Committee (HICPAC). 1995; 123:250-9. tion of the Surgical Care Improvement www.cdc.gov/mmwr/PDF/RR/ 83. Sastry V, Brennan PJ, Levy MM. Project at a teaching medical center. RR4412.PDF (accessed 2012 Dec 9). Vancomycin-resistant enterococci: an Am J Surg. 2009; 198:881-8. 71. Gould FK, Brindle R, Chadwick PR emerging problem in immunosup- 56. Parker BM, Henderson JM, Vitagliano et al. Guidelines (2008) for the pro- pressed transplant recipients. Trans- S et al. Six sigma methodology can be phylaxis and treatment of methicillin- plant Proc. 1995; 27:954-5.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 259 ASHP Report Antimicrobial prophylaxis

84. Rhinehart E, Smith NE, Wennersten C. phylaxis for a surgical procedure? Ann efficacy with reduced nephrotoxicity? Rapid dissemination of beta-lactamase Surg. 2008; 247:927-8. Ren Fail. 1992; 14:1-9. producing aminoglycoside resistant 99. Goldman DA, Hopkins CC, Karchmer 114. Anaya DA, Dellinger EP. The obese Enterococcus faecium among patients AW et al. Cephalothin prophylaxis in surgical patient: a susceptible host for and staff on an infant-toddler surgical cardiac valve surgery. A prospective, infection. Surg Infect. 2006; 7:473-80. ward. N Engl J Med. 1990; 323:1814-8. double-blind comparison of two-day 115. Waisbren E, Rosen H, Bader AM et 85. Cohen SH, Gerding DN, Johnson S and six-day regimens. J Thorac Cardio- al. Percent body fat and prediction of et al. Clinical practice guidelines for vasc Surg. 1977; 73:470-9. surgical site infection. J Am Coll Surg. Clostridium difficile infection in adults: 100. Platt R, Munoz A, Stella J et al. Antibi- 2010; 210:381-9. 2010 update by the Society for Health- otic prophylaxis for cardiovascular sur- 116. Engelman R, Shahian D, Shemin R et care Epidemiology of America (SHEA) gery. Efficacy with coronary artery by- al. The Society of Thoracic Surgeons and the Infectious Diseases Society of pass. Ann Intern Med. 1984; 101:770-4. practice guideline series: antibiotic America (IDSA). Infect Control Hosp 101. Forse RA, Karam B, MacLean LD et al. prophylaxis in cardiac surgery, part Epidemiol. 2010; 31:431-55. Antibiotic prophylaxis for surgery in II: antibiotic choice. Ann Thorac Surg. 86. Salkind AR, Cuddy PG, Foxworth JW. morbidly obese patients. Surgery. 1989; 2007; 83:1569-76. Is this patient allergic to penicillin? An 106:750-6. 117. Zanetti G, Giardina R, Platt R. Intraop- evidence-based analysis of the likeli- 102. Falagas ME, Karageorgopoulos DE. erative redosing of cefazolin and risk for hood of penicillin allergy. JAMA. 2001; Adjustment of dosing of antimicrobial surgical site infection in cardiac surgery. 285:2498-505. agents for bodyweight in adults. Lan- Emerg Infect Dis. 2001; 7:828-31. 87. Frumin J, Gallagher JC. Allergic cross- cet. 2010; 375:248-51. 118. Scher KS. Studies on the duration of sensitivity between penicillin, carbape- 103. Pai MP, Bearden DT. Antimicrobial antibiotic administration for surgical nem, and monobactam antibiotics: dosing considerations in obese adult prophylaxis. Am Surg. 1997; 63:59-62. what are the chances? Ann Pharmaco- patients. Insights from the Society of 119. Markantonis SL, Kostopanagiotou G, ther. 2009; 43:304-15. Infectious Diseases Pharmacists. Phar- Panidis D et al. Effects of blood loss 88. Cunha BA. Antibiotic selection in the macotherapy. 2007; 27:1081-91. and fluid volume replacement on penicillin-allergic patient. Med Clin 104. Johnson PN, Miller JL, Boucher EA, serum and tissue gentamicin concen North Am. 2006; 90:1257-64. for the Pediatric Pharmacy Advisory trations during colorectal surgery. Clin 89. Pichichero ME. Use of selected cepha- Group Advocacy Committee. Medica- Ther. 2004; 26:271-81. losporins in penicillin-allergic patients: tion dosing in overweight and obese 120. Morita S, Nishisho I, Nomura T et al. a paradigm shift. Diagn Microbiol Infect children. www.ppag.org/obesedose The significance of the intraoperative Dis. 2007; 57:13s-18s. (accessed 2010 Nov 22). repeated dosing of antimicrobials for 90. Galandiuk S, Polk HC Jr, Jagelman DG 105. Koopman E, Nix DE, Erstad BL et al. preventing surgical wound infection et al. Re-emphasis of priorities in surgi- End-of-procedure cefazolin concentra- in colorectal surgery. Surg Today. 2005; cal antibiotic prophylaxis. Surg Gynecol tions after administration for preven- 35:732-8. Obstet. 1989; 169:218-22. tion of surgical-site infection. Am J 121. Swoboda SM, Merz C, Kostuik J et al. 91. DiPiro JT, Vallner JJ, Bowden TA et Health-Syst Pharm. 2007; 64:1927-34. Does intraoperative blood loss affect al. Intraoperative serum and tissue 106. Bauer LA, Edwards WA, Dellinger antibiotic serum and tissue concen trations? 1996; 131:1165-72. activity of cefazolin and cefoxitin. Arch EP et al. Influence of weight on ami- Arch Surg. Surg. 1985; 120:829-32. noglycoside pharmacokinetics in 122. DiPiro JT, Cheung RP, Bowden TA et 92. Classen DC, Evans RS, Pestotnik SL et normal weight and morbidly obese al. Single-dose systemic antibiotic pro- al. The timing of prophylactic admin patients. Eur J Clin Pharmacol. 1983; phylaxis of surgical wound infections. istration of antibiotics and the risk 24:643-7. Am J Surg. 1986; 152:552-9. 107. Bailey TC, Little JR, Littenberg B et al. of surgical-wound infection. N Engl J 123. Fonseca SN, Kunzle SR, Junqueira A meta-analysis of extended-interval Implementing 1-dose anti- Med. 1992; 326:281-6. MJ et al. dosing versus multiple daily dosing of biotic prophylaxis for prevention of 93. Garey KW, Dao T, Chen H et al. Timing of vancomycin prophylaxis for aminoglycosides. Clin Infect Dis. 1997; surgical site infection. Arch Surg. 2006; 141:1109-13. cardiac surgery patients and the risk 24:786-95. 124. McDonald M, Grabsch E, Marshall C et of surgical site infections. 108. Barza M, Ioannidis JP, Cappelleri JC J Antimicrob al. Single- versus multiple-dose antimi- 2006; 58:645-50. et al. Single or multiple daily doses of Chemother. crobial prophylaxis for major surgery: 94. Steinberg JP, Braun BI, Hellinger WC et aminoglycosides: a meta-analysis. BMJ. a systematic review. al. Timing of antimicrobial prophylaxis 1996; 312:338-45. Aust N Z J Surg. 1998; 68:388-96. and the risk of surgical site infection: 109. Blaser J, Konig C. Once-daily dosing of aminoglycosides. 125. Kreter B, Woods M. Antibiotic pro- results from the Trial to Reduce An- Eur J Clin Microbiol Infect Dis. 1995; 14:1029-38. phylaxis for cardiothoracic operations. timicrobial Prophylaxis Errors. Ann Meta-analysis of thirty years of clinical 2009; 250:10-6. 110. Murry KR, McKinnon PS, Mitrzyk B Surg. Pharmacodynamic characteriza- trials. J Thorac Cardiovasc Surg. 1992; 95. Van Kasteren ME, Mannien J, Ott A et et al. tion of nephrotoxicity associated with 104:590-9. al. Antibiotic prophylaxis and the risk once-daily aminoglycoside. 126. Austin TW, Coles JC, Burnett R et al. of surgical site infections following to- Pharmaco- therapy. 1999; 19:1252-60. Aortocoronary bypass procedures and tal hip arthroplasty: timely administra- sternotomy infections: a study of anti- tion is the most important factor. 111. Nicolau DP, Freeman CD, Belliveau PP Clin et al. Experience with a once-daily ami- staphylococcal prophylaxis. Can J Surg. Infect Dis. 2007; 44:921-7. noglycoside program administered to 1980; 23:483-5. 96. Soriano A, Bori G, Garcia-Ramiro S 2,184 adult patients. Antimicrob Agents 127. Galbraith U, Schilling J, Von Segesser Timing of antibiotic prophylaxis et al. Chemother. 1995; 39:650-5. LK et al. Antibiotic prophylaxis in car- for primary total knee arthroplasty 112. Rao SC, Ahmed M, Hagan R. One dose diovascular surgery: a prospective, ran- performed during ischemia. Clin Infect per day compared to multiple doses domized, comparative trial of one-day Dis. 2008; 46:1009-14. per day of gentamicin for treatment of cefazolin vs single-dose cefuroxime. 97. Weber WP, Marti WR, Zwahlen M et suspected or proven sepsis in neonates. Drugs Exp Clin Res. 1993; 19:229-34. al. The timing of surgical antimicrobial Cochrane Database Syst Rev. 2006; 128. Kriaras I, Michalopoulos A, Michalis prophylaxis. Ann Surg. 2008; 247:918-26. 1:CD005091. A et al. Antibiotic prophylaxis in car- 98. Dellinger EP. What is the ideal time for 113. Zhanel GG, Ariano RE. Once daily diac surgery. J Cardiovasc Surg. 1997; administration of antimicrobial pro- aminoglycoside dosing: maintained 38:605-10.

260 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

129. Kriaras I, Michalopoulos A, Turina M tion by application of topical vanco- sert. Research Triangle Park, NC: et al. Evolution of antimicrobial pro- mycin. J Thorac Cardiovasc Surg. 1989; GlaxoSmithKline; 2009 Apr. phylaxis in cardiovascular surgery. Eur 98:618-22. 157. Kallen AJ, Wilson CT, Larson RJ. Peri- J Cardiothorac Surg. 2000; 18:440-6. 143. Bennett-Guerrero E, Ferguson TB Jr, operative intranasal mupirocin for the 130. Harbarth S, Samore MH, Lichtenberg Lin M et al. Effect of an implantable prevention of surgical-site infections: D et al. Prolonged antibiotic prophy- gentamicin-collagen sponge on sternal systematic review of the literature and laxis after cardiovascular surgery and wound infections following cardiac meta-analysis. Infect Control Hosp Epi- its effect on surgical site infections and surgery: a randomized trial. JAMA. demiol. 2005; 26:916-22. antimicrobial resistance. Circulation. 2010; 304:755-62. 158. Van Rijen M, Bonten M, Wenzel R et 2000; 101:2916-21. 144. Bennett-Guerrero E, Pappas TN, Koltun al. Mupirocin ointment for preventing 131. Edwards FH, Engelman R, Houck P et WA et al. Gentamicin-collagen sponge Staphylococcus aureus infections in al. The Society of Thoracic Surgeons for infection prophylaxis in colorectal nasal carriers. Cochrane Database Syst practice guideline series: antibiotic surgery. N Engl J Med. 2010; 363:1038- Rev. 2008; 4:CD006216. prophylaxis in cardiac surgery, part 49. 159. Hebert C, Robicsek A. Decolonization I: duration. Ann Thorac Surg. 2006; 145. McHugh SM, Collins CJ, Corrigan therapy in infection control. Curr Opin 81:397-404. MA et al. The role of topical antibiot- Infect Dis. 2010; 23:340-5. 132. Lee KR, Ring JC, Leggiadro RJ. Pro- ics used as prophylaxis in surgical site 160. Perl TM, Cullen JJ, Wenzel RP et al. phylactic antibiotic use in pediatric infection prevention. J Antimicrob Intranasal mupirocin to prevent post- cardiovascular surgery: a surgery of Chemother. 2011; 66:693-701. operative Staphylococcus aureus infec- current practice. Pediatr Infect Dis J. 146. Goodman J, Schaffner W, Collins H et tions. N Engl J Med. 2002; 346:1871-7. 1995; 14:267-9. al. Infection after cardiovascular sur- 161. Konvalinka A, Errett L, Fong IW. Im- 133. American Academy of Orthopaedic gery. N Engl J Med. 1968; 278:117-23. pact of treating Staphylococcus aureus Surgeons. Information statement: rec- 147. Perl TM. Prevention of Staphylococcus nasal carriers on wound infections in ommendations for the use of intrave- aureus infections among surgical pa- cardiac surgery. J Hosp Infect. 2006; nous antibiotic prophylaxis in primary tients: beyond traditional perioperative 64:162-8. total joint arthroplasty. www.aaos.org/ prophylaxis. Surgery. 2003; 134:s10-7. 162. Bode LG, Kluytmans JA, Wertheim HF about/papers/advistmt/1027.asp (ac- 148. Kluytmans JA, Mouton JW, Ijzerman et al. Preventing surgical-site infections cessed 2008 May 13). EP et al. Nasal carriage of Staphylococ- in nasal carriers of Staphylococcus au- 134. McCarthy PJ, Patil S, Conrad SA et cus aureus as a major risk factor for reus. N Engl J Med. 2010; 362:9-17. al. International and specialty trends wound infections after cardiac surgery. 163. Lee AS, Macedo-Vinas M, Francois P et in the use of prophylactic antibiotics J Infect Dis. 1995; 171:216-9. al. Impact of combined low-level mu- to prevent infectious complications 149. Kluytmans JA, Mouton JW, Vanden- pirocin and genotypic chlorhexidine after insertion of external ventricular Bergh MF et al. Reduction of surgical- resistance on persistent methicillin- drainage devices. Neurocrit Care. 2010; site infections in cardiothoracic sur- resistant Staphylococcus aureus carriage 12:220-4. gery by elimination of nasal carriage after decolonization therapy: a case- 135. Hares MM, Hegarty MA, Warlow J et of Staphylococcus aureus. Infect Control control study. Clin Infect Dis. 2011; al. A controlled trial to compare sys- Hosp Epidemiol. 1996; 17:780-5. 52:1422-30. temic and intra-incisional cefuroxime 150. Kalmeijer MD, Coertjens H, Van 164. Muto CA, Jernigan JA, Ostrowsky BE prophylaxis in high risk gastric surgery. Nieuwland-Bollen PM et al. Surgical et al. SHEA guideline for preventing Br J Surg. 1981; 68:276-80. site infections in orthopedic surgery: nosocomial transmission of multi- 136. Moesgaard F, Lykkegaard Nielsen M. the effect of mupirocin nasal oint- drug-resistant strains of Staphylococcus Failure of topically applied antibiot- ment in a double-blind, randomized, aureus and Enterococcus. Infect Control ics, added to systemic prophylaxis, placebo-controlled study. Clin Infect Hosp Epidemiol. 2003; 24:362-86. to reduce perineal wound infection Dis. 2002; 35:353-8. 165. Edwards JR, Peterson KD, Mu Y et al. in abdominoperineal excision of 151. Hacek DM, Robb WJ, Paule SM et al. National Healthcare Safety Network the rectum. Acta Chir Scand. 1988; Staphylococcus aureus nasal decolo- (NHSN) report: data summary for 154:589-92. nization in joint replacement surgery 2006 through 2008. Am J Infect Control. 137. Pitt HA, Postier RG, Gadacz TR et al. reduces infection. Clin Orthop Relat 2009; 37:783-805. The role of topical antibiotics in “high- Res. 2008; 466:1349-55. 166. Kutsal A, Ibrisim E, Catav Z et al. risk” biliary surgery. Surgery. 1982; 152. White A, Smith J. Nasal reservoir as Mediastinitis after open heart surgery. 91:518-24. the source of extranasal staphylococci. Analysis of risk factors and manage- 138. Pitt HA, Postier RG, Mcgowan WA et Antimicrob Agents Chemother. 1963; ment. J Cardiovasc Surg. 1991; 32:38- al. Prophylactic antibiotics in vascular 161:679-83. 41. surgery. Topical, systemic, or both. Ann 153. Lauderdale TL, Wang JT, Lee WS et al. 167. Abboud CS, Way SB, Baltar VT. Risk Surg. 1980; 192:356-64. Carriage rates of methicillin-resistant factors for mediastinitis after car- 139. Schersten H. Modified prophylaxis Staphylococcus aureus (MRSA) depend diac surgery. Ann Thorac Surg. 2004; for preventing deep sternal wound on anatomic location, the number of 77:676-83. infection after cardiac surgery. APMIS. sites cultured, culture methods, and the 168. Crabtree TD, Codd JE, Fraser VJ et al. 2007; 115:1023-6. distribution of clonotypes. Eur J Clin Multivariate analysis of risk factors for 140. Friberg Ö, Svedjeholm R, Söderquist B Microbiol Infect Dis. 2010; 29:1553-9. deep and superficial sternal infection et al. Local gentamicin reduces sternal 154. Jain R, Kralovic SM, Evans ME. after coronary artery bypass graft- wound infections after cardiac surgery: Veterans Affairs initiative to pre- ing at a tertiary care medical center. a randomized controlled trial. Ann vent Staphylococcus aureus infections. Semin Thorac Cardiovasc Surg. 2004; Thorac Surg. 2005; 79:153-62. N Engl J Med. 2011; 364:1419-30. 16:53-61. 141. Eklund AM, Valtonen M, Werkkala 155. Harbarth S, Fankhauser C, Schrenzel J 169. Kohli M, Yuan L, Escobar M et al. A KA. Prophylaxis of sternal wound et al. Univeral screening for methicillin- risk index for sternal surgical wound infections with gentamicin-collagen resistant Staphylococcus aureus at hos- infection after cardiovascular surgery. implant: randomized controlled study pital admission and nosocomial infec- Infect Control Hosp Epidemiol. 2003; in cardiac surgery. J Hosp Infect. 2005; tion in surgical patients. JAMA. 2008; 24:17-25. 59:108-12. 299:1149-57. 170. Lepelletier D, Perron S, Bizouarn P et 142. Vander Salm TJ, Okike ON, Pasque 156. Bactroban (mupirocin calcium al. Surgical-site infection after cardiac MK et al. Reduction of sternal infec- ointment, 2%) nasal package in- surgery: incidence, microbiology and

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 261 ASHP Report Antimicrobial prophylaxis

risk factors. Infect Control Hosp Epide- complicating open-heart operations. 199. Doebbeling BN, Pfaller MA, Kuhns miol. 2005; 26:466-72. Antimicrob Agents Chemother. 1963; KR et al. Cardiovascular surgery pro- 171. Lu JC, Grayson AD, Jha P et al. Risk 3:731-5. phylaxis: a randomized, controlled factors for sternal wound infection and 186. Garey KW, Amrutkar P, Dao-Tran TK comparison of cefazolin and cefurox- mid-term survival following coronary et al. Economic benefit of appropri- ime. J Thorac Cardiovasc Surg. 1990; artery bypass surgery. Eur J Cardiotho- ate timing of vancomycin prophylaxis 99:981-9. rac Surg. 2003; 23:943-9. in patients undergoing cardiovascu- 200. Vuorisalo S, Pokela R, Syrjälä H. Com- 172. Tang GH, Maganti M, Weisel RD et al. lar surgery. Pharmacotherapy. 2008; parison of vancomycin and cefuroxime Prevention and management of deep 28:699-706. for infection prophylaxis in coronary sternal wound infection. Semin Thorac 187. Garey KW, Lai D, Dao-Tran TK et artery bypass surgery. Infect Control Cardiovasc Surg. 2004; 16:62-9. al. Interrupted time series analysis of Hosp Epidemiol. 1998; 19:234-9. 173. Jakob HG, Borneff-Lipp M, Bach A et vancomycin compared to cefuroxime 201. Baddour LM, Bettmann MA, Bolger al. The endogenous pathway is a major for surgical prophylaxis in patients un- AF et al. Nonvalvular cardiovascular route for deep sternal wound infec- dergoing cardiac surgery. Antimicrob device-related infections. Circulation. tion. Eur J Cardiothorac Surg. 2000; Agents Chemother. 2008; 52:446-51. 2003; 108:2015-31. 17:154-60. 188. Cimochowski GE, Harostock MD, 202. Chamber CE, Eisenhauer MD, McNicol 174. Rahmanian PB, Adams DH, Castillo Brown R et al. Intranasal mupirocin LB et al. Infection control guidelines for JG et al. Impact of body mass index reduces sternal wound infection after the cardiac catheterization laboratory: on early outcome and late survival in open heart surgery in diabetics and society guidelines revisited. Catheter patients undergoing coronary artery nondiabetics. Ann Thorac Surg. 2001; Cardiovasc Interv. 2006; 67:78-86. bypass grafting or valve surgery or 71:1572-9. 203. Van Rijen M, Bonten M, Wenzel R et both. Am J Cardiol. 2007; 100:1702-8. 189. Zangrillo A, Landoni G, Fumagalli L et al. Mupirocin ointment for preventing 175. Vuorisalo S, Haukipuro K, Pokela R et al. Methicillin-resistant Staphylococcus Staphylococcus aureus infections in al. Risk features for surgical-site infec- species in a cardiac surgical intensive nasal carriers. Cochrane Database Syst tions in coronary artery bypass surgery. care unit: a 5-year experience. J Cardio- Rev. 2008; 4:CD006216. Infect Control Hosp Epidemiol. 1998; thorac Vasc Anesth. 2006; 20:31-7. 204. Ortega GM, Martí-Bonmatí E, 19:240-7. 190. Fekety F, Cluff L, Sabiston D et al. A Guevara SJ et al. Alteration of van- 176. Segers P, De Jong AP, Kloek JJ et al. study of antibiotic prophylaxis in car- comycin pharmacokinetics during Risk control of surgical site infection diac surgery. J Thorac Cardiovasc Surg. cardiopulmonary bypass in patients after cardiothoracic surgery. J Hosp 1969; 57:757-63 undergoing cardiac surgery. Am J Infect. 2006; 62:437-45. 191. Conte J, Cohen S, Roe B et al. Antibi- Health-Syst Pharm. 2003; 60:260-5. 177. Zerr KJ, Furnary AP, Grunkemeier GL otic prophylaxis and cardiac surgery: a 205. Nascimento JW, Carmona MJ, et al. Glucose control lowers the risk of prospective double-blind comparison Strabelli TM et al. Systemic availability wound infection in diabetics after open of single-dose versus multi-dose regi- of prophylactic cefuroxime in patients heart operations. Ann Thorac Surg. mens. Ann Intern Med. 1972; 76:943-9. submitted to coronary artery bypass 1997; 63:356-61. 192. Firor W. Infection following open- grafting with cardiopulmonary bypass. 178. Furnary AP, Zerr KJ, Grunkemeier GL heart surgery, with special reference to J Hosp Infect. 2005; 59:299-303. et al. Continuous intravenous insulin the role of prophylactic antibiotics. J 206. Vuorisalo S, Pokela R, Syrjälä H. Is infusion reduces the incidence of deep Thorac Cardiovasc Surg. 1967; 53:371-8. single-dose antibiotic prophylaxis sternal wound infection in diabetic pa- 193. Slama T, Sklar S, Misinski J et al. Ran- sufficient for coronary artery bypass tients after cardiac surgical procedures. domized comparison of cefamandole, surgery? An analysis of peri- and Ann Thorac Surg. 1999; 67:352-62. cefazolin and cefuroxime prophy- postoperative serum cefuroxime and 179. Dellinger EP. Preventing surgical-site laxis in open-heart surgery. Antimicrob vancomycin levels. J Hosp Infect. 1997; infections: the importance of timing Agents Chemother. 1986; 29:744-7. 37:237-47. and glucose control. Infect Control 194. Kaiser A, Petracek M, Lea J et al. Ef- 207. Fellinger EK, Leavitt BJ, Hebert JC. Hosp Epidemiol. 2001; 22:604-6. ficacy of cefazolin, cefamandole, and Serum levels of prophylactic cefazolin 180. Latham R, Lancaster AD, Covington JF gentamicin as prophylactic agents during cardiopulmonary bypass sur- et al. The association of diabetes and in cardiac surgery. Ann Surg. 1987; gery. Ann Thorac Surg. 2002; 74:1187- glucose control with surgical-site in- 206:791-7. 90. fections among cardiothoracic surgery 195. Conklin C, Gray R, Neilson D et al. 208. Caffarelli AD, Holden JP, Baron EJ et patients. Infect Control Hosp Epidemiol. Determinants of wound infection inal. Plasma cefazolin levels during car- 2001; 22:607-12. cidence after isolated coronary artery diovascular surgery: effects of cardio- 181. Furnary AP, Gao G, Grunkemeier GL bypass surgery in patients randomized pulmonary bypass and profound hy- et al. Continuous insulin infusion to receive prophylactic cefuroxime pothermic circulatory arrest. J Thorac reduces mortality in patients with or cefazolin. Ann Thorac Surg. 1988; Cardiovasc Surg. 2006; 131:1338-43. diabetes undergoing coronary artery 46:172-7. 209. Hutschala D, Skhirtladze K, Kinstner C bypass grafting. J Thorac Cardiovasc 196. Wellens F, Pirlet M, Larbuisson R et et al. In vivo microdialysis to measure Surg. 2003; 125:1007-21. al. Prophylaxis in cardiac surgery: a antibiotic penetration into soft tissue 182. Gandhi GY, Nuttall GA, Abel MD et controlled, randomized comparison during cardiac surgery. Ann Thorac al. Intraoperative hyperglycemia and between cefazolin and cefuroxime. Eur Surg. 2007; 84:1605-10. perioperative outcomes in cardiac J Cardiothorac Surg. 1995; 9:325-9. 210. Waltrip T, Lewis R, Young V et al. A surgery patients. Mayo Clin Proc. 2005; 197. Townsend TR, Reitz BA, Bilker WB et pilot study to determine the feasibility 80:862-6. al. Clinical trial of cefamandole, cefazo- of continuous cefazolin infusion. Surg 183. Dohmen PM. Influence of skin flora lin, and cefuroxime for antibiotic pro- Infect. 2002; 3:5-9. and preventive measures on surgical phylaxis in cardiac operations. J Thorac 211. Nascimento JW, Carmona MJ, Strabelli site infection during cardiac surgery. Cardiovasc Surg. 1993; 106:664-70. TM et al. Perioperative cefuroxime Surg Infect. 2006; 7:S13-7. 198. Curtis JJ, Boley TM, Walls JT et al. pharmacokinetics in cardiac surgery. 184. Kittle C, Reed W. Antibiotics and extra- Randomized, prospective comparison Clinics. 2007; 62:257-60. corporeal circulation. J Thorac Cardio- of first- and second-generation ceph 212. Lewis DR, Longman TJ, Wisheart JD vasc Surg. 1961; 41:34-48. alosporins as infection prophylaxis et al. The pharmacokinetics of a single 185. Slonim R, Litwak R, Gadboys H et al. for cardiac surgery. Am J Surg. 1993; dose of gentamicin (4 mg/kg) as pro- Antibiotic prophylaxis of infection 166:734-7. phylaxis in cardiac surgery requiring

262 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

cardiopulmonary bypass. Cardiovasc update on valvular heart disease: fo- 240. Rovera F, Imperatori A, Militello P et Surg. 1999; 7:398-401. cused update on infective endocarditis: al. Infections in 346 consecutive video- 213. Kitzes-Cohen R, Farin D, Piva G et a report of the American College of assisted thoracoscopic procedures. Surg al. Pharmacokinetics of vancomycin Cardiology/American Heart Associa- Infect. 2003; 4:45-51. administered as prophylaxis before tion Task Force on Practice Guidelines. 241. Turna A, Kutlu CA, Ozalp T et al. An- cardiac surgery. Ther Drug Monit. 2000; Circulation. 2008; 118:887-96. tibiotic prophylaxis in elective thoracic 22:661-7. 229. Baddour LM, Epstein AE, Erickson surgery: cefuroxime versus cefepime. 214. Austin T, Coles J, McKenzie P et al. CC et al. American Heart Associa- Thorac Cardiov Surg. 2003; 51:84-8. Cephalothin prophylaxis and valve tion Rheumatic Fever, Endocarditis, 242. Boldt J, Piper S, Uphus D et al. Preop- replacement. Ann Thorac Surg. 1977; and Kawasaki Disease Committee; erative microbiologic screening and 23:333-6. Council on Cardiovascular Disease antibiotic prophylaxis in pulmonary 215. Sisto T, Laurikka J, Tarkka MR. Ceftri- in Young; Council on Cardiovascular resection operations. Ann Thorac Surg. axone vs cefuroxime for infection pro- Surgery and Anesthesia; Council on 1999; 68:208-11. phylaxis in coronary bypass surgery. Cardiovascular Nursing; Council on 243. Schussler O, Dermine H, Alifano M Scand J Thorac Cardiovasc Surg. 1994; Clinical Cardiology; Interdisciplinary et al. Should we change antibiotic 28:143-8. Council on Quality of Care; American prophylaxis for lung surgery? Postop- 216. Nooyen SM, Overbeek BP, Brutel De Heart Association. Update on cardio- erative pneumonia is the critical issue. La Riviere A et al. Prospective ran- vascular implantable electronic device Ann Thorac Surg. 2008; 86:1727-34. domised comparison of single-dose infections and their management: a 244. Shiono S, Yoshida J, Nishimura M et al. versus multiple-dose cefuroxime for scientific statement from the American Risk factors of postoperative respira- prophylaxis in coronary artery bypass Heart Association. Circulation. 2010; tory infections in lung cancer surgery. grafting. Eur J Clin Microbiol Infect Dis. 121:458-77. J Thorac Oncol. 2007; 2:34-8. 1994; 13:1033-7. 230. Klug D, Balde M, Pavin D et al. Risk 245. Imperatori A, Rotolo N, Gatti M et al. 217. Tamayo E, Gualis J, Flórez S et al. factors related to infections of im- Peri-operative complications of video- Comparative study of single-dose and planted pacemakers and cardioverter- assisted thoracoscopic surgery (VATS). 24-hour multiple-dose antibiotic pro- defibrillators: results of a large pro- Int J Surg. 2008; 6:S78-81. phylaxis for cardiac surgery. J Thorac spective study. Circulation. 2007; 246. Solaini L, Prusciano F, Bagioni P et al. Cardiovasc Surg. 2008; 136:1522-7. 116:1349-55. Video-assisted thoracic surgery (VATS) 218. Mertz D, Johnstone J, Loeb M. Does 231. De Oliveira JC, Martinelli M, Nishioka of the lung: analysis of intraoperative duration of perioperative antibiotic SA et al. Efficacy of antibiotic pro- and postoperative complications over prophylaxis matter in cardiac surgery? phylaxis before the implantation 15 years and review of the literature. A systematic review and meta-analysis. of pacemakers and cardioverter- Surg Endosc. 2008; 22:298-310. Ann Surg. 2011; 254:48-54. defibrillators: results of a large, pro- 247. Imperatori A, Rovera F, Rotolo N et al. 219. Sandoe JA, Kumar B, Stoddart B et spective, randomized, double-blinded, Prospective study of infection risk fac- al. Effect of extended perioperative placebo-controlled trial. Circ Arrhythm tors in 988 lung resections. Surg Infect. antibiotic prophylaxis on intravascular Electrophysiol. 2009; 2:29-34. 2006; 7:S57-60. catheter colonization and infection 232. Sohail MR, Uslan DZ, Khan AH et al. 248. Chamberlain RS, Sakpal SV. A com- in cardiothoracic surgery patients. Risk factor analysis of permanent pace- prehensive review of single-incision J Antimicrob Chemother. 2003; 52:877-9. maker infection. Clin Infect Dis. 2007; laparoscopic surgery (SILS) and natu- 220. Niederhäuser U, Vogt M, Vogt P et al. 45:166-73. ral orifice transluminal endoscopic Cardiac surgery in a high-risk group 233. Bertaglia E, Zerbo F, Zardo S et al. Anti- surgery (NOTES) techniques for of patients: is prolonged postoperative biotic prophylaxis with a single dose of chelecystectomy. J Gastrointest Surg. antibiotic prophylaxis effective? J Tho- cefazolin during pacemaker implanta- 2009; 13:1733-40. rac Cardiovasc Surg. 1997; 114:162-8. tion: incidence of long-term infective 249. Cruse PJ, Foord R. The epidemiology 221. Huddleston CB. Mediastinal wound complications. PACE. 2006; 29:29-33. of wound infection: a ten-year pro- infections following pediatric cardiac 234. Holman WL, Pae WE, Teutenberg JJ et spective study of 62,939 wounds. Surg surgery. Semin Thorac Cardiovasc Surg. al. INTERMACS: interval analysis of Clin North Am. 1980; 60:27-40. 2004; 16:108-12. registry data. J Am Coll Cardiol. 2009; 250. Petrosillo N, Drapeau CM, Nicastri E 222. McEvoy GK, Snow EK, Miller J et al., 208:755-61. et al. Surgical site infections in Italian eds. AHFS drug information. Bethesda, 235. Walker PC, DePrestel DD, Miles NA et hospitals: a prospective multicenter MD: American Society of Health- al. Surgical infection prophylaxis for study. BMC Infect Dis. 2008; 8:34. System Pharmacists; 2011. left ventricular assist device implanta- 251. Watanabe A, Kohnoe S, Shimabukuro 223. Johns Hopkins Hospital, Arcara K, tion. J Card Surg. 2011; 26:440-3. R et al. Risk factors associated with sur- Tschudy M, Lee CK, eds. Harriet Lane 236. Califano S, Pagani FD, Malani PN. Left gical site infection in upper and lower handbook, 19th edition. Philadelphia: ventricular assist device-associated gastrointestinal surgery. Surg Today. Elsevier, Inc.; 2012. infections. Infect Dis Clin North Am. 2008; 38:404-12. 224. Lance LL, Lacey CF, Goldman MP et 2012; 26:77-87. 252. Yasuda K, Shiraishi N, Adachi Y et al. al., eds. Quick-look drug book, 18th 237. Radu DM, Jauréguy F, Seguin A et al. Risk factors for complications follow- edition. Baltimore, MD: Lippincott Postoperative pneumonia after major ing resection of large gastric cancer. Williams & Wilkins; 2011. pulmonary resections: an unsolved Br J Surg. 2001; 88:873-7. 225. Lexi-Comp Online. Hudson, OH: Lexi- problem in thoracic surgery. Ann Tho- 253. Mohri Y, Tonouchi H, Kobayashi M et Comp, Inc.; 2011. rac Surg. 2007; 84:1669-74. al. Randomized clinical trial of single- 226. Smith KM, Riche DM, Henyan NN, 238. Cardo D, Horan T, Andres M et al. versus multiple-dose antimicrobial eds. Handbook of clinical drug data. National Nosocomial Infections Sur- prophylaxis in gastric cancer surgery. 11th ed. New York: McGrawHill; 2010. veillance (NNIS) system report: data Br J Surg. 2007; 94:683-8. 227. Da Costa A, Kirkorian G, Cucherat summary from January 1992 through 254. Yeo CJ, Cameron JL, Sohn TA et al. M et al. Antibiotic prophylaxis for June 2004. Am J Infect Control. 2004; Pancreaticoduodenectomy with or permanent pacemaker implantation: 32:470-85. without extended retroperitoneal a meta-analysis. Circulation. 1998; 239. Aznar R, Mateu M, Miró JM et al. Anti- lymphadenectomy for periampullary 97:1796-801. biotic prophylaxis in non-cardiac tho- adenocarcinoma: comparison of mor- 228. Nishimura RA, Carabello BA, Faxon racic surgery: cefazolin versus placebo. bidity and mortality and short-term DP et al. ACC/AHA 2008 guideline Eur J Cardiothorac Surg. 1991; 5:515-8. outcome. Ann Surg. 1999; 229:613-24.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 263 ASHP Report Antimicrobial prophylaxis

255. Jafri NS, Mahid SS, Minor KS et al. 271. Stone HH. Gastric surgery. South Med 285. Banerjee S, Shen B, Baron TH, for the Meta-analysis: antibiotic prophylaxis J. 1977; 70:S35-7. American Society for Gastrointestinal to prevent peristomal infection follow- 272. Morris DL, Yound D, Burdon DW et al. Endoscopy Standards of Practice Com- ing percutaneous endoscopic gastros- Prospective randomized trial of single- mittee. Antibiotic prophylaxis for GI tomy. Aliment Pharmacol Ther. 2007; dose cefuroxime against mezlocillin in endoscopy. Gastrointest Endosc. 2008; 25:647-56. elective gastric surgery. J Hosp Infect. 67:791-8. 256. Sharma VK, Howden CW. Meta- 1984; 5:200-4. 286. Rey JR, Axone A, Budzynska A et al. analysis of randomized, controlled 273. Lewis RT, Allan CM, Goodall RG et al. Guidelines of the European Society of trials of antibiotic prophylaxis before Discriminate use of antibiotic prophy- Gastrointestinal Endoscopy (E.S.G.E.) percutaneous endoscopic gastrostomy. laxis in gastroduodenal surgery. Am J antibiotic prophylaxis for gastroin- Am J Gastroenterol. 2000; 95:3133-6. Surg. 1979; 138:640-3. testinal endoscopy. Endoscopy. 1998; 257. Gorbach SL, Plaut AG, Nahas L et al. 274. Lewis RT, Allan CM, Goodall RG et 30:318-24. Studies of intestinal microflora: II. al. Cefamandole in gastroduodenal 287. Allison MC, Sandoe JA, Tighe R et al., Microorganisms of the small intestine surgery: a controlled prospective, ran- for the Endoscopy Committee of the and their relations to oral fecal flora. domized, double-blind study. Can J British Society of Gastroenterology. Gastroenterology. 1967; 53:856-67. Surg. 1982; 25:561-3. Antibiotic prophylaxis in gastrointes- 258. Gorbach SL. Intestinal microflora.Gas - 275. Mitchell NJ, Evans DS, Pollock D. tinal endoscopy. Gut. 2009; 58:869-80. troenterology. 1971; 60:1110-29. Pre-operative, single-dose cefuroxime 288. Gossner L, Keymling J, Hahn EG et al. 259. Ruddell WS, Axon AT, Findlay JM et antimicrobial prophylaxis with and Antibiotic prophylaxis in percutane- al. Effect of cimetidine on the gastric without metronidazole in elective ous endoscopic gastrostomy (PEG): a bacterial flora.Lancet. 1980; 1:672-4. gastrointestinal surgery. J Antimicrob prospective randomized clinical trial. 260. Driks MR, Craven DE, Bartolome Chemother. 1980; 6:393-9. Endoscopy. 1999; 31:119-24. RC et al. Nosocomial pneumonia in 276. Uchiyama K, Takifuji K, Tani M et al. 289. Rao GG, Osman M, Johnson L et al. intubated patients given sucralfate as Prevention of postoperative infections Prevention of percutaneous endo compared with antacids or histamine by administration of antimicrobial scopic gastrostomy site infections type 2 blockers. N Engl J Med. 1987; agents immediately before surgery for caused by methicillin-resistant Staphy- 317:1376-82. patients with gastrointestinal cancers. lococcus aureus. J Hosp Infect. 2004; 261. Long J, Desantis S, State D et al. Hepatogastroenterology. 2007; 54:1487- 58:81-3. The effect of antisecretagogues on 93. 290. Thomas S, Cantrill S, Waghorn DJ et gastric microflora.Arch Surg. 1983; 277. Pories WJ, Van Rij AM, Burlingham al. The role of screening and antibiotic 118:1413-5. BT et al. Prophylactic cefazolin in prophylaxis in the prevention of per- 262. Sjostedt S, Levin P, Malmborg AS et al. gastric bypass surgery. Surgery. 1981; cutaneous gastrostomy site infection Septic complications in relation to fac- 90:426-32. caused by methicillin-resistant Staphy- tors influencing the gastric microflora 278. Polk H, Lopez-Meyer J. Postoperative lococcus aureus. Aliment Pharmacol in patients undergoing gastric surgery. wound infection: a prospective study Ther. 2007; 25:593-7. J Hosp Infect. 1989; 12:191-7. of determinant factors and prevention. 291. Sauerland S, Angrisani L, Belachew M 263. Feretis CB, Contou CT, Papoutsis GG Surgery. 1969; 66:97-103. et al. Obesity surgery. Evidence-based et al. The effect of preoperative treat- 279. Saadeddin A, Freshwater DA, Fisher guidelines of the European Association ment with cimetidine on postoperative NC et al. Antibiotic prophylaxis for for Endoscopic Surgery (EAES). Surg wound sepsis. Am Surg. 1984; 50:594-8. percutaneous endoscopic gastros- Endosc. 2005; 19:200-21. 264. Antimicrobial prophylaxis in surgery. tomy for non-malignant conditions: a 292. Varela JE, Wilson SE, Nguyen NT. Treat Guidel Med Lett. 2006; 4:83-8. double-blind prospective randomized Laparoscopic surgery significantly 265. LoCiero J, Nichols RL. Sepsis after gas- controlled trial. Aliment Pharmacol reduces surgical-site infections com- troduodenal operations; relationship Ther. 2005; 22:565-70. pared with open surgery. Surg Endosc. to gastric acid, motility, and endog- 280. Ahmad I, Mouncher A, Abdoolah A et 2010; 24:270-6. enous microflora.South Med J. 1980; al. Antibiotic prophylaxis for percu- 293. Ueno T, Yamamoto K, Kawaoka T et 73:878-80. taneous endoscopic gastrostomy—a al. Current antibiotic prophylaxis in 266. Pessaux P, Msika S, Atalla D et al. Risk prospective, randomized, double-blind pancreatoduodenectomy in Japan. factors for postoperative infectious trial. Aliment Pharmacol Ther. 2003; J Hepatobiliary Pancreat Surg. 2005; complications in noncolorectal ab- 18:209-15. 12:304-9. dominal surgery: a multivariate analy- 281. Dormann AJ, Wigginghaus B, Risius 294. Stone HH, Haney BH, Kolb LD et al. sis based on a prospective multicenter H et al. Antibiotic prophylaxis in per- Prophylactic and preventive antibi- study of 4718 patients. Arch Surg. 2003; cutaneous endoscopic gastrostomy otic therapy. Timing, duration and 138:314-24. (PEG)—results from a prospective economics. Ann Surg. 1979; 189:691-9. 267. Imai E, Ueda M, Kanao K et al. Surgical randomized multicenter trial. Z Gas- 295. Kusachi S, Sumiyama Y, Nagao J et al. site infection surveillance after open troenterol. 2000; 38:229-34. Prophylactic antibiotics given within gastrectomy and risk factors for surgi- 282. Preclik G, Grüne S, Leser HG et al. 24 hours of surgery, compared with an- cal site infection. J Infect Chemother. Prospective, randomized, double blind tibiotics given for 72 hours periopera- 2005; 11:141-5. trial of p rophylaxis with single dose tively, increased the rate of methicillin- 268. Christou NV, Jarand J, Sylvestre JL et of co-amoxiclav before percutaneous resistant Staphylococcus aureus isolated al. Analysis of the incidence and risk endoscopic gastrostomy. BMJ. 1999; from surgical site infections. J Infect factors for wound infections in open 319:881-4. Chemother. 2008; 14:44-50. bariatric surgery. Obes Surg. 2004; 283. Panigrahi H, Shreeve DR, Tan WC 296. Imamura H, Furukawa H, Iijima S 14:16-22. et al. Role of antibiotic prophylaxis et al. Multicenter phase II study of 269. McArdle CS, Morran CG, Pettit L et for wound infection in percutaneous antimicrobial prophylaxis in low-risk al. Value of oral antibiotic prophylaxis endoscopic gastrostomy (PEG): result patients undergoing distal gastrectomy in colorectal surgery. Br J Surg. 1995; of a prospective double-blind random- for gastric cancer. Gastric Cancer. 2006; 82:1046-8. ized trial. J Hosp Infect. 2002; 50:312-5. 9:32-5. 270. Nichols RL, Webb WR, Jones JW et al. 284. Sturgis TM, Yancy W, Cole JC et al. 297. Alexander JW, Rahn R. Prevention of Efficacy of antibiotic prophylaxis in Antibiotic prophylaxis in percutaneous deep wound infection in morbidly high risk gastroduodenal operations. endoscopic gastrostomy. Am J Gastro- obese patients by infusion of an anti- Am J Surg. 1982; 143:94-8. enterol. 1996; 91:2301-4. biotic into the subcutaneous space at

264 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

the time of wound closure. Obes Surg. 311. Rotermann M. Infection after chole- 325. Brill A, Ghosh K, Gunnarsson C et al. 2004; 14:970-4. cystectomy, hysterectomy or appendec- The effects of laparoscopic cholecys- 298. Radhakrishnan NV, Shenoy AH, tomy. Health Rep. 2004; 15:11-23. tectomy, hysterectomy, and appendec- Cartmill I et al. Addition of local an- 312. Chang WT, Lee KT, Chuang SC et al. tomy on nosocomial infection risks. tiseptic spray to parenteral antibiotic The impact of prophylactic antibiotics Surg Endosc. 2008; 22:1112-8. regimen reduces the incidence of sto- on postoperative infection complica- 326. Cainzos M, Potel J, Puente JL. Prospec- mal infection following percutaneous tion in elective laparoscopic chole tive, randomized, controlled study of endoscopic gastrostomy: a randomized cystectomy: a prospective randomized prophylaxis with cefamandole in high- controlled trial. Eur J Gastroenterol study. Am J Surg. 2006; 191:721-5. risk patients undergoing operations Hepatol. 2006; 18:1279-84. 313. Zhou H, Zhang J, Wang Q et al. upon the biliary tract. Surg Gynecol 299. Bates T, Roberts JV, Smith K et al. A Meta-analysis: antibiotic prophylaxis Obstet. 1985; 160:27-32. randomized trial of one versus three in elective laparoscopic cholecystec- 327. Meijer WS, Schmitz PI. Prophylactic doses of augmentin as wound pro- tomy. Aliment Pharmacol Ther. 2009; use of cefuroxime in biliary tract sur- phylaxis in at-risk abdominal surgery. 29:1086-95. gery: randomized, controlled trial of Postgrad Med J. 1992; 68:811-6. 314. Dobay KJ, Freier DT, Albear P. The single versus multiple dose in high-risk 300. McArdle CS, Morran CG, Anderson JR absent role of prophylactic antibiotics patients. Br J Surg. 1993; 80:917-21. et al. Oral ciprofloxacin as prophylaxis in low-risk patients undergoing lapa- 328. Grant MD, Jones RC, Wilson SE et al. in gastroduodenal surgery. J Hosp In- roscopic cholecystectomy. Am Surg. Single-dose cephalosporin prophylaxis fect. 1995; 30:211-6. 1999; 65:226-8. in high-risk patients undergoing surgi- 301. Rawat D, Srivistava A, Thomson M. 315. Higgins A, London J, Charland S et cal treatment of the biliary tract. Surg Antibody prophylaxis for children al. Prophylactic antibiotics for elective Gynecol Obstet. 1992; 174:347-54. undergoing percutaneous endoscopic laparoscopic cholecystectomy: are they 329. Lapointe RW, Roy AF, Turgeon PL et al. gastrostomy. J Pediatr Gastroenterol necessary? Arch Surg. 1999; 134:611-4. Comparison of single-dose cefotetan Nutr. 2005; 40:234-5. 316. Tocchi A, Lepre L, Costa G et al. The and multidose cefoxitin as intravenous 302. Cortes A, Sauvanet A, Bert F et al. need for antibiotic prophylaxis in elec- prophylaxis in elective, open biliary Effect of bile contamination on imme- tive laparoscopic cholecystectomy: a tract surgery: a multicentre, double- diate outcomes after pancreaticoduo- prospective randomized study. Arch blind, randomized study. Can J Surg. denectomy for tumor. J Am Coll Surg. Surg. 2000; 135:67-70. 1994; 37:313-8. 2006; 202:93-9. 317. Guzmán-Valdivia G. Routine admin- 330. Strachan CJ, Black J, Powis SJ et al. 303. Solomkin JS, Mazuski JE, Bradley JS istration of antibiotics to patients Prophylactic use of cephazolin against et al. Diagnosis and management of suffering accidental gallbladder perfo- wound sepsis after cholecystectomy. Br complicated intra-abdominal infection ration during laparoscopic cholecys- Med J. 1977; 1:1254-6. in adults and children: guidelines by tectomy is not necessary. Surg Laparosc 331. Berne TV, Yellin AE, Appleman MD the Surgical Infection Society and the Endosc Percutan Tech. 2008; 18:547-50. et al. Controlled comparison of ce- Infectious Diseases Society of America. 318. Harling R, Moorjani N, Perry C et al. A fmetazole with cefoxitin for prophy- Surg Infect. 2010; 11:79-109. prospective, randomized trial of pro- laxis in elective cholecystectomy. Surg 304. Meijer WS, Schmitz PI, Jeekel J. Meta- phylactic antibiotics versus bag extrac- Gynecol Obstet. 1990; 170:137-40. analysis of randomized, controlled tion in the prophylaxis of wound infec- 332. Wilson SE, Hopkins JA, Williams RA. clinical trials of antibiotic prophylaxis tion in laparoscopic cholecystectomy. A comparison of cefotaxime versus in biliary tract surgery. Br J Surg. 1990; Ann R Coll Surg Engl. 2000; 82:408-10. cefamandole in prophylaxis for surgi- 77:282-90. 319. Illig KA, Schmidt E, Cavanaugh J et cal treatment of the biliary tract. Surg 305. Den Hoed PT, Boelhouwer RU, Veen al. Are prophylactic antibiotics re- Gynecol Obstet. 1987; 164:207-12. HF et al. Infections and bacteriologi- quired for elective laparoscopic cho- 333. Kujath P. Antibiotic prophylaxis in cal data after laparoscopic and open lecystectomy? J Am Coll Surg. 1997; biliary tract surgery. Ciprofloxacin gallbladder surgery. J Hosp Infect. 1998; 184:353-6. versus ceftriaxone. Am J Med. 1989; 39:27-37. 320. Zurbuchen U, Ritz JP, Lehmann KS 87(5A):255S-257S. 306. Dervisoglou A, Tsiodras S, Kanel- et al. Oral vs intravenous antibiotic 334. Garibaldi RA, Skolnck D, Maglio S et lakopoulou K et al. The value of che- prophylaxis in elective laparoscopic al. Postcholecystectomy wound infec- moprophylaxis against Enterococcus cholecystectomy—an exploratory trial. tion. Ann Surg. 1986; 204:650-4. species in elective cholecystectomy: a Langenbecks Arch Surg. 2008; 393:479- 335. Levi JU, Martinez OV, Hutson DG et randomized study of cefuroxime vs 85. al. Ampicillin versus cefamandole in ampicillin/sulbactam. Arch Surg. 2006; 321. Al-Abassi AA, Farghaly MM, Ahmed biliary tract surgery. Am Surg. 1984; 141:1162-7. HL et al. Infection after laparoscopic 50:412-7. 307. Cainzos M, Sayek I, Wacha H et al. cholecystectomy: effect of infected bile 336. Kellum JM, Duma RJ, Gorbach SL et Septic complications after biliary and infected gallbladder wall. Eur J al. Single-dose antibiotic prophylaxis tract stone surgery: a review and Surg. 2001; 167:268-73. for biliary surgery. Arch Surg. 1987; report of the European Prospective 322. Farello GA, Cerofolini A. Antimicro- 122:918-22. Study. Hepatogastroenterology. 1997; bial prophylaxis with ceftriaxone in 337. Muller EL, Pitt HA, Thompson JE 44:959-67. laparoscopic cholecystectomy: a 7-year et al. Antibiotics in infections of the 308. Lippert H, Gastinger J. Antimicrobial clinical experience involving 3,603 biliary tract. Surg Gynecol Obstet. 1987; prophylaxis in laparoscopic and con- patients. J Chemother. 2000; 12(suppl 165:285-92. ventional cholecystectomy. Chemo- 3):17-22. 338. Jewesson PJ, Stiver G, Wai A et al. therapy. 1998; 44:355-63. 323. McGuckin M, Shea JA, Schwartz JS. Double-blind comparison of cefazolin 309. Siddiqui K, Khan AF. Comparison of Infection and antimicrobial use in lap- and ceftizoxime for prophylaxis against frequency of wound infection: open aroscopic cholecystectomy. Infect Con- infections following elective biliary vs laparoscopic cholecystectomy. J trol Hosp Epidemiol. 1999; 20:624-6. tract surgery. Antimicrob Agents Che- Ayub Med Coll Abbottabad. 2006; 324. Biscione FM, Couto RC, Pedrosa TM mother. 1996; 40:70-4. 18:21-4. et al. Comparison of the risk of surgical 339. Montravers P, Lepape A, Dubreuil L et 310. Romy S, Eisenring MC, Bettschart V et site infection after laparoscopic chole- al. Clinical and microbiological profiles al. Laparoscope use and surgical site in- cystectomy and open cholecystectomy. of community-acquired and noso- fections in digestive surgery. Ann Surg. Infect Control Hosp Epidemiol. 2007; comial intra-abdominal infections: 2008; 247:627-32. 28:1103-6. results of the French prospective, ob-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 265 ASHP Report Antimicrobial prophylaxis

servational EBIIA study. J Antimicrob 351. Krige JE, Isaacs S, Stapleton GN et al. of brief antibiotic prophylaxis. Arch Chemother. 2009; 63:785-94. Prospective, randomized study com- Surg. 1983; 118:651-5. 340. Baquero F, Hsueh PR, Paterson DL et paring amoxicillin-clavulanic acid and 365. Tonz M, Schmid P, Kaiser G. Antibiotic al. In vitro susceptibilities of aerobic cefamandole for the prevention of prophylaxis for appendectomy in chil- and facultatively anaerobic gram- wound infection in high-risk patients dren: critical appraisal. World J Surg. negative bacilli isolated from pa- undergoing elective biliary surgery. 2000; 24:995-8. tients with intra-abdominal infections J Hosp Infect. 1992; 22(suppl A):33- 366. Wilson AP. Antibiotic prophylaxis and worldwide: 2005 results from Study for 41. infection control measures in mini- Monitoring Antimicrobial Resistance 352. Agrawal CS, Sehgal R, Singh RK et al. mally invasive surgery. J Antimicrob Trends (SMART). Surg Infect. 2009; Antibiotic prophylaxis in elective cho- Chemother. 1995; 36:1-5. 10:99-104. lecystectomy: a randomized, double 367. Aziz O, Athanasiou T, Tekkis PP. Lapa- 341. Chow JW, Satishchandran V, Snyder blind study comparing ciprofloxacin roscopic versus open appendectomy TA et al. In vitro susceptibilities of and cefuroxime. Indian J Physiol Phar- in children: a meta-analysis. Ann Surg. aerobic and facultative gram-negative macol. 1999; 43:501-4. 2006; 243:17-27. bacilli isolated from patients with 353. Kellum JM, Gargano S, Gorbach SL et 368. Khan MN, Fayyad T, Cecil TD et al. intra-abdominal infections worldwide: al. Antibiotic prophylaxis in high-risk Laparoscopic versus open appendecto- the 2002 Study for Monitoring Anti- biliary operations: multicenter trial of my: the risk of postoperative infectious microbial Resistance Trends (SMART). single preoperative ceftriaxone versus complications. JSLS. 2007; 11:363-7. Surg Infect. 2005; 6:439-48. multidose cefazolin. Am J Surg. 1984; 369. Hansen J, Smithers MB, Schache D et 342. Choudhary A, Bechtold ML, Puli SR et 148:15-21. al. Laparoscopic versus open appen- al. Role of prophylactic antibiotics in 354. Tonelli F, Mazzei T, Novelli A et al. dectomy: prospective randomised trial. laparoscopic cholecystectomy: a meta- Amoxicillin/clavulanic acid versus World J Surg. 1996; 20:17-21. analysis. J Gastrointest Surg. 2008; cefotaxime for antimicrobial pro- 370. Sauerland S, Lefering R, Neugebauer 12:1847-53. phylaxis in abdominal surgery: a EA. Laparoscopic versus open surgery 343. Stone HH, Hooper CA, Kolb LD et randomized trial. J Chemother. 2002; for suspected appendicitis. Cochrane al. Antibiotic prophylaxis in gastric, 14:366-72. Database Syst Rev. 2004; 4:CD001546. biliary and colonic surgery. Ann Surg. 355. McLeish AR, Keighley MR, Bishop 371. Hemmila MR, Birkmeyer NJ, Arbabi S 1976; 184:443-52. HM. Selecting patients requiring anti- et al. Introduction to propensity scores: 344. Sirinek KR, Schauer PR, Yellin AE biotics in biliary surgery by immediate a case study on the comparative effec- et al. Single-dose cefuroxime versus Gram stains of bile at surgery. Surgery. tiveness of laparoscopic vs open appen- multiple-dose cefazolin as prophylactic 1977; 81:473-7. dectomy. Arch Surg. 2010; 145:939-45. therapy for high-risk cholecystectomy. 356. Krajden S, Yaman M, Fuksa M et al. 372. Stone HH. Bacterial flora of appendi- J Am Coll Surg. 1994; 178:321-5. Piperacillin versus cefazolin given citis in children. J Pediatr Surg. 1976; 345. Drumm J, Donovan IA, Wise R. A com- perioperatively to high-risk patients 11:37-42. parison of cefotetan and cefazolin for who undergo open cholecystectomy: a 373. Keighley MR. Infection: prophylaxis. prophylaxis against wound infection double-blind, randomized trial. Can J Br Med Bull. 1988; 44:374-402. after elective cholecystectomy. J Hosp Surg. 1993; 36:245-50. 374. Andersen BR, Kallehave FL, Andersen Infect. 1985; 6:277-80. 357. McArdle CS. Oral prophylaxis in HK. Antibiotics versus placebo for pre- 346. Crenshaw CA, Glanges E, Webber biliary tract surgery. J Antimicrob Che- vention of postoperative infection after CE et al. A prospective, randomized, mother. 1994; 33:200-2. appendicectomy. Cochrane Database double-blind study of preventive 358. Plouffe JF, Perkins RL, Fass RJ et al. Syst Rev. 2005; 3:CD001439. cefamandole therapy in patients at Comparison of the effectiveness of 375. Helmer KS, Robinson EK, Lally KP et high risk for undergoing cholecys- moxalactam and cefazolin in the al. Standardized patient care guidelines tectomy. Surg Gynecol Obstet. 1981; prevention of infection in patients un- reduce infectious morbidity in ap- 153:546-52. dergoing abdominal operations. Diagn pendectomy patients. Am J Surg. 2002; 347. Leaper DJ, Cooper MJ, Turner A. A Microbiol Infect Dis. 1985; 3:25-31. 183:608-13. comparison trial between cefotetan 359. Katz S, Glicksman A, Levy Y et al. Cefu- 376. Lau WY, Fan ST, Yiu TF et al. Pro- and cephazolin for wound sepsis roxime prophylaxis in biliary surgery: phylaxis of post-appendectomy sepsis prophylaxis during elective upper gas- single versus triple dose. Israel J Med by metronidazole and cefotaxime: a trointestinal surgery with an investiga- Sci. 1993; 29:673-6. randomized, prospective and double- tion of cefotetan penetration into the 360. Ahmed ME, Ibrahim SZ, Arabi YE et blind trial. Br J Surg. 1983; 70:670-2. obstructed biliary tree. J Hosp Infect. al. Metronidazole prophylaxis in acute 377. Lau WY, Fan ST, Chu KW et al. Ran- 1986; 7:269-76. mural appendicitis: failure of a single domized, prospective, and double- 348. Maki DG, Lammers JL, Aughey DR. intra-operative infusion to reduce blind trial of new beta-lactams Comparative studies of multiple-dose wound infection. J Hosp Infect. 1987; in the treatment of appendicitis. cefoxitin vs. single-dose cefonicid for 10:260-4. Antimicrob Agents Chemother. 1985; surgical prophylaxis in patients under- 361. Donovan IA, Ellis D, Gatehouse D 28:639-42. going biliary tract operations or hys- et al. One-dose antibiotic prophy- 378. Lau WY, Fan ST, Chu KW et al. Cefoxi- terectomy. Rev Infect Dis. 1984; 6(suppl laxis against wound infection after tin versus gentamicin and metronida- 4):S887-95. appendectomy: a randomized trial of zole in prevention of post-appendectomy 349. Garcia-Rodriquez JA, Puig-LaCalle J, clindamycin, cefazolin sodium and a sepsis: a randomized, prospective trial. J Arnau C et al. Antibiotic prophylaxis placebo. Br J Surg. 1979; 66:193-6. Antimicrob Chemother. 1986; 18:613-9. with cefotaxime in gastroduodenal 362. Gilmore OJ, Martin TD. Aetiology 379. O’Rourke MG, Wynne MJ, Morahan RJ and biliary surgery. Am J Surg. 1989; and prevention of wound infection et al. Prophylactic antibiotics in appen- 158:428-32. in appendectomy. Br J Surg. 1974; dectomy: a prospective, double-blind, 350. Targarona EM, Garau J, Munoz- 62:567-72. randomized study. Aust N Z J Surg. Ramos C et al. Single-dose antibiotic 363. Keiser TA, Mackenzie RL, Feld LN. 1984; 54:535-41. prophylaxis in patients at high risk for Prophylactic metronidazole in appen- 380. Liberman MA, Greason KL, Frame S infection in biliary surgery: a prospec- dectomy: a double-blind controlled et al. Single-dose cefotetan or cefoxi- tive and randomized study comparing trial. Surgery. 1983; 93:201-3. tin versus multiple-dose cefoxitin as cefonicid with mezlocillin. Surgery. 364. Winslow RE, Rem D, Harley JW. Acute prophylaxis in patients undergoing 1990; 107:327-34. nonperforating appendicitis: efficacy appendectomy for acute nonperforated

266 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

appendicitis. J Am Coll Surg. 1995; sis of 1446 patients. Arch Surg. 2006; 410. Forbes SS, Eskicioglu C, McLeod RS 180:77-80. 141:1014-8. et al. Meta-analysis of randomized 381. Salam IM, Abu Galala KH, el Ashaal 395. Salim A, Teixeira PG, Inaba K et al. controlled trials comparing open and YI et al. A randomized prospective Analysis of 178 penetrating stomach laparoscopic ventral and incisional study of cefoxitin versus piperacillin and small bowel injuries. World J Surg. hernia repair with mesh. Br J Surg. in appendicectomy. J Hosp Infect. 1994; 2008; 32:471-5. 2009; 96:851-8. 26:133-6. 396. Witzke JD, Kraatz JJ, Morken JM et al. 411. Sanchez VM, Abi-Haidar YE, Itani 382. Lau WY, Fan ST, Yiu TF et al. Pro- Stapled versus hand sewn anastomoses KM. Mesh infection in ventral inci- phylaxis of postappendectomy sepsis in patients with small bowel injury: a sional hernia repair: incidence, con- by metronidazole and ampicillin: a changing perspective. J Trauma. 2000; tributing factors, and treatment. Surg randomized, prospective and double- 49:660-6. Infect. 2011; 12:205-9. blind trial. Br J Surg. 1983; 70:155-7. 397. Kirkpatrick AW, Baxter KA, Simons RK 412. Itani KM, Wilson SE, Awad SS et al. Er- 383. Al-Dhohayan A, Al-Sebayl M, Shibl et al. Intraabdominal complications af- tapenem versus cefotetan prophylaxis A et al. Comparative study of ter surgical repair of small bowel inju- in elective colorectal surgery. N Engl J Augmentin versus metronidazole/ ries: an international review. J Trauma. Med. 2006; 335:2640-51. gentamicin in the prevention of infec- 2003; 55:399-406. 413. Bartlett S, Burton R. Effects of prophy- tions after appendectomy. Eur Surg Res. 398. Brundage SI, Jurkovich GJ, Hoyt DB et lactic antibiotics on wound infection 1993; 25:60-4. al. Stapled versus sutured gastrointesti- after elective colon and rectal surgery. 384. Morris WT, Innes DB, Richardson nal anastomoses in the trauma patient: Am J Surg. 1983; 145:300-9. RA et al. The prevention of post- a multicenter trial. J Trauma. 2001; 414. Burton RC. Postoperative wound in- appendicectomy sepsis by metroni- 51:1054-61. fection in colon and rectal surgery. Br J dazole and cefazolin: a controlled 399. Hackam DJ, Ali J, Jastaniah SS. Effects Surg. 1973; 60:363-8. double-blind trial. Aust N Z J Surg. of other intraabdominal injuries on the 415. Baum M, Anish D, Chalmers T et al. 1980; 50:429-33. diagnosis, management, and outcome A survey of clinical trials of antibiotic 385. Morris DL, Wilson SR, Pain J et of small bowel trauma. J Trauma. 2000; prophylaxis in colon surgery: evidence al. A comparison of aztreonam/ 49:606-10. against further use of no treatment metronidazole and cefotaxime/ 400. Guarino J, Hassett JM Jr, Luchette FA. controls. N Engl J Med. 1981; 305:795-9. metronidazole in elective colorectal Small bowel injuries: mechanisms, pat- 416. Coppa G, Eng K, Gouge T et al. Par- surgery: antimicrobial prophylaxis terns, and outcome. J Trauma. 1995; enteral and oral antibiotics in elec- must include gram-positive cover. 39:1076-80. tive colorectal surgery: a prospective J Antimicrob Chemother. 1990; 25:673-8. 401. Schnuriger B, Inaba K, Eberle BM et al. randomized trial. Am J Surg. 1983; 386. Mui LM, Ng CS, Wong SK et al. Opti- Microbiological profile and antimicro- 145:62-5. mum duration of prophylactic antibi- bial susceptibility in surgical site infec- 417. Coppa G, Eng K. Factors involved in otics in acute non-perforated appendi- tions following hollow viscus injury. antibiotic selection in elective colon citis. Aust N Z J Surg. 2005; 75; 425-8. J Gastrointest Surg. 2010; 14:1304-10. and rectal surgery. Surgery. 1988; 387. Kasatpibal N, Nørgaard M, Sørensen 402. Múñez E, Ramos A, Espejo TÁ et al. 104:853-8. HT et al. Risk of surgical site infection [Microbiology of surgical site infec- 418. Glenny AM, Song F. Antimicrobial and efficacy of antibiotic prophylaxis: a tions in abdominal tract surgery prophylaxis in colorectal surgery. Qual cohort study of appendectomy patients patients]. Cir Esp. 2011; 89:606-12. In Health Care. 1999; 8:132-6. in Thailand. BMC Infect Dis. 2006; Spanish. 419. Suding P, Jensen E, Abramson MA et 6:111. 403. Den Hartog D, Dur AH, Tuinebreijer al. Definitive risk factors for anasto- 388. Nadler EP, Gaines BA. The Surgical WE et al. Open surgical procedures for motic leaks in elective open colorectal Infection Society guidelines on anti- incisional hernias. Cochrane Database resection. Arch Surg. 2008; 143:907-12. microbial therapy for children with Syst Rev. 2008; 3:CD006438. 420. Svensson LG. Prophylactic antimicro- appendicitis. Surg Infect. 2008; 9:75-83. 404. Sanchez-Manuel FJ, Lozano-García J, bial administration. S Afr J Surg. 1985; 389. Kizilcan F, Tanyel FC, Buyukpamukcu Seco-Gil JL. Antibiotic prophylaxis for 23:55-62. N et al. The necessity of prophylactic hernia repair. Cochrane Database Syst 421. Hojer H, Wetterfors J. Systemic pro- antibiotics in uncomplicated appendi- Rev. 2012; 2:CD003769. phylaxis with doxycycline in surgery of citis during childhood. J Pediatr Surg. 405. Yin Y, Song T, Liao B et al. Antibi- the colon and rectum. Ann Surg. 1978; 1992; 27:586-8. otic prophylaxis in patients undergoing 187:362-8. 390. Soderquist-Elinder C, Hirsch K, open mesh repair of inguinal hernia: a 422. Kurz A, Sessler DI, Lenhardt R, for the Bergdahl S et al. Prophylactic antibiot- meta-analysis. Am Surg. 2012; 78:359- Study of Wound Infection and Tem- ics in uncomplicated appendicitis dur- 65. perature Group. Perioperative nor- ing childhood: a prospective random- 406. Goodney PP, Birkmeyer CM, Birkmeyer mothermia to reduce the incidence of ized study. Eur J Pediatr Surg. 1995; JD. Short-term outcomes of laparo- surgical-wound infection and shorten 5:282-5. scopic and open ventral hernia repair: hospitalization. N Engl J Med. 1996; 391. Browder W, Smith JW, Vivoda LM et a meta-analysis. Arch Surg. 2002; 137: 334:1209-15. al. Nonperforative appendicitis: a con- 1161-5. 423. Ata A, Lee J, Bestle SL et al. Postop- tinuing surgical dilemma. J Infect Dis. 407. Sajid MS, Bokhari SA, Mallick AS et erative hyperglycemia and surgical site 1989; 159:1088-94. al. Laparoscopic versus open repair infection in general surgery patients. 392. Emil S, Laberge JM, Mikhail P et al. of incisional/ventral hernia: a meta- Arch Surg. 2010; 145:858-64. Appendicitis in children: a ten-year up- analysis. Am J Surg. 2009; 197:64-72. 424. McConnell YJ, Johnson PM, Porter date of therapeutic recommendations. 408. Kaafarani HM, Kaufman D, Reda D et GA. Surgical site infections following J Pediatr Surg. 2003; 38:236-42. al. Predictors of surgical site infection colorectal surgery in patients with 393. Leong G, Wilson J, Charlett A. Dura- in laparoscopic and open ventral inci- diabetes: association with postopera- tion of operation as a risk factor for sional herniorrhaphy. J Surg Res. 2010; tive hyperglycemia. J Gastrointest Surg. surgical site infection: comparison 163:229-34. 2009; 13:508-15. of English and US data. J Hosp Infect. 409. Itani KM, Hur K, Kim LT et al. Com- 425. Nichols RL. Prophylaxis for intraab- 2006; 63:255-62. parison of laparoscopic and open dominal surgery. Rev Infect Dis. 1984; 394. Walz MJ, Paterson CA, Seligowski JM repair with mesh for the treatment of 6(suppl 1):S276-82. et al. Surgical site infection following ventral incisional hernia: a randomized 426. Nelson RL, Glenny AM, Song F. An- bowel surgery: a retrospective analy- trial. Arch Surg. 2010; 145:322-8. timicrobial prophylaxis for colorectal

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 267 ASHP Report Antimicrobial prophylaxis

surgery. Cochrane Database Syst Rev. in elective colonic surgery: a controlled 453. Hoffman C, McDonald P, Watts J. Use 2009; 1:CD001181. trial. Lancet. 1975; 2:997-9. of perioperative cefoxitin to prevent 427. Clarke J, Condon R, Bartlett J et al. Pre- 440. Washington J, Dearing W, Judd E et infection after colonic and rectal sur- operative oral antibiotics reduce septic al. Effect of preoperative antibiotic gery. Ann Surg. 1981; 193:353-6. complications of colon operations: regimen on development of infection 454. Periti P, Mazzei T, Tonelli F. Single-dose results of a prospective randomized, after intestinal surgery. Ann Surg. 1974; cefotetan vs multiple dose cefoxitin. double-blind clinical study. Ann Surg. 180:567-72. Rectum. 1989; 32:121-7. 1977; 186:251-9. 441. Peruzzo L, Savio S, De Lalla F. Systemic 455. Jagelman D, Fabian T, Nichols R et 428. Nichols R, Broldo P, Condon P et versus systemic plus oral chemopro- al. Single-dose cefotetan versus mul- al. Effect of preoperative neomycin- phylaxis in elective colorectal surgery. tiple dose cefoxitin as prophylaxis in erythromycin intestinal preparation on Chemioterapia. 1987; 6:601-3. colorectal surgery. Am J Surg. 1988; the incidence of infectious complica- 442. Willis A, Fergunson I, Jones P et al. 155:71-6. tions following colon surgery. Ann Metronidazole in prevention and 456. Shatney CH. Antibiotic prophylaxis in Surg. 1973; 178:453-62. treatment of Bacteroides infections in elective gastrointestinal tract surgery: 429. Stellato T, Danziger L, Gordon N et al. elective colonic surgery. Br Med J. 1977; a comparison of single-dose preop- Antibiotics in elective colon surgery: a 1:607-10. erative cefotaxime and multiple-dose randomized trial of oral, systemic, and 443. Hagen TB, Bergan T, Liavag I. Pro- cefoxitin. J Antimicrob Chemother. oral/systemic antibiotics for prophy- phylactic metronidazole in elective 1984; 14(suppl B):241-5. laxis. Am Surg. 1990; 56:251-4. colorectal surgery. Acta Chir Scand. 457. Arnaud JP, Bellissant E, Boissel P et al. 430. Petrelli N, Contre DC, Herrera L et 1980; 146:71-5. Single-dose amoxycillin-clavulanic al. A prospective randomized trial of 444. Song F, Glenny AM. Antimicrobial acid vs cefotetan for prophylaxis in perioperative prophylactic cefaman- prophylaxis in colorectal surgery: elective colorectal surgery: a multicen- dole in elective colorectal surgery for a systematic review of randomized tre, prospective, randomized study. malignancy. Dis Colon Rectum. 1988; controlled trials. Br J Surg. 1998; J Hosp Infect. 1992; 22(suppl A):23- 31:427-9. 85:1232-41. 32. 431. Kling PA, Dahlgren S. Oral prophylaxis 445. Kaiser A, Herrington J, Jacobs J et al. 458. Periti P, Tonelli F, Mazzei T et al. Anti- with neomycin and erythromycin in Cefoxitin vs erythromycin, neomycin microbial chemoimmunoprophylaxis colorectal surgery; more proof for ef- and cefazolin in colorectal surgery: in colorectal surgery with cefotetan ficacy than failure.Arch Surg. 1989; importance of the duration of the and thymostimulin: prospective, con- 124:705-7. operative procedure. Ann Surg. 1983; trolled, multicenter study. J Chemother. 432. Lewis RT, Goodall RG, Marien B et 198:525-30. 1993; 5:37-42. al. Is neomycin necessary for bowel 446. Weaver M, Burdon DW, Youngs DJ et 459. Skipper D, Karran SJ. A randomized, preparation in surgery of the colon? al. Oral neomycin and erythromycin prospective study to compare cefotetan Oral neomycin plus erythromycin ver- compared with single-dose systemic with cefuroxime plus metronidazole as sus erythromycin–metronidazole. Dis metronidazole and ceftriaxone pro- prophylaxis in elective colorectal sur- Colon Rectum. 1989; 32:265-70. phylaxis in elective colorectal surgery. gery. J Hosp Infect. 1992; 21:73-7. 433. Wapnick S, Gunito R, Leveen HH et al. Am J Surg. 1986; 151:437-42. 460. Lumley JW, Siu SK, Pillay SP et al. Reduction of postoperative infection 447. Keighley MR, Arabi Y, Alexander- Single-dose ceftriaxone as prophylaxis in elective colorectal surgery with pre- Williams J et al. Comparison between for sepsis in colorectal surgery. Aust N operative administration of kanamycin systemic and oral antimicrobial pro- Z J Surg. 1992; 62:292-6. and erythromycin. Surgery. 1979; phylaxis in colorectal surgery. Lancet. 461. Hakansson T, Raahave D, Hansen OH 85:317-21. 1979; 1:894-7. et al. Effectiveness of single-dose pro- 434. Bartlett J, Condon R, Gorbach S et al. 448. Lewis RT, Allan CM, Goodall RG et phylaxis with cefotaxime and metro- Veterans Administration Cooperative al. Are first-generation cephalosporins nidazole compared with three doses of Study on bowel preparation for elective effective for antibiotic prophylaxis in cefotaxime alone in elective colorectal colorectal operations: impact of oral elective surgery of the colon? Can J surgery. Eur J Surg. 1993; 159:177-80. antibiotic regimen on colonic flora, Surg. 1983; 26:504-7. 462. Karran SJ, Sutton G, Gartell P et al. wound irrigation cultures and bacte- 449. Condon RE, Bartlett JG, Nichols RL et Imipenem prophylaxis in elective riology of septic complications. Ann al. Preoperative prophylactic cephalo- colorectal surgery. Br J Surg. 1993; Surg. 1978; 188:249-54. thin fails to control septic complica- 80:1196-8. 435. Wolff B, Beart R, Dozios R et al. A new tions of colorectal operations: results 463. Fukatsu K, Saito H, Matsuda T et al. bowel preparation for elective colon of a controlled clinical trial. Am J Surg. Influences of type and duration of an- and rectal surgery: a prospective, ran- 1979; 137:68-74. timicrobial prophylaxis on an outbreak domized clinical trial. Arch Surg. 1988; 450. McDermott F, Polyglase A, Johnson W of methicillin-resistant Staphylococcus 123:895-900. et al. Prevention of wound infection aureus and on the incidence of wound 436. Gahhos FN, Richards GK, Hinchey EJ in colorectal resections by preop- infection. Arch Surg. 1997; 132:1320-5. et al. Elective colon surgery: clindamy- erative cephazolin with and without 464. AhChong K, Yip AW, Lee FC et al. Com- cin versus metronidazole prophylaxis. metronidazole. Aust N Z J Surg. 1981; parison of prophylactic ampicillin/ Can J Surg. 1982; 25:613-6. 51:351-3. sulbactam with gentamicin and metro- 437. Dion YM, Richards GK, Prentis JJ et 451. Jones RN, Wojeski W, Bakke J et al. An- nidazole in elective colorectal surgery: al. The influence of oral metronida- tibiotic prophylaxis to 1,036 patients a randomized clinical study. J Hosp zole versus parenteral preoperative undergoing elective surgical proce- Infect. 1994; 27:149-54. metronidazole on sepsis follow- dures. A prospective randomized com- 465. Kwok SP, Lau WY, Leung KL et al. ing colon surgery. Ann Surg. 1980; parative trial of cefazolin, cefoxitin, Amoxicillin and clavulanic acid versus 192:221-6. and cefotaxime in a prepaid medical cefotaxime and metronidazole as anti- 438. Beggs FD, Jobanputra RS, Holmes practice. Am J Surg. 1987; 153:341-6. biotic prophylaxis in elective colorectal JT. A comparison of intravenous and 452. Morton A, Taylor E, Wells G. A mul- resectional surgery. Chemotherapy. oral metronidazole as prophylactic ticenter study to compare cefotetan 1993; 39:135-9. in colorectal surgery. Br J Surg. 1982; alone with cefotetan and metronida- 466. Barbar MS, Hirxberg BC, Rice C et al. 69:226-7. zole as prophylaxis against infection Parenteral antibiotics in elective colon 439. Goldring J, McNaught W, Scott A et al. in elective colorectal operations. Surg surgery? A prospective, controlled Prophylactic oral antimicrobial agents Gynecol Obstet. 1989; 169:41-5. clinical study. Surgery. 1979; 86:23-9.

268 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

467. Madsen M, Toftgaard C, Gaversen H et blind study of 10% mannitol me- 495. Johnson JT, Yu VL, Myers EN et al. al. Cefoxitin for one day vs ampicillin chanical bowel preparation combined Efficacy of two third-generation cepha- and metronidazole for three days in with oral neomycin and short-term, losporins in prophylaxis for head and elective colorectal surgery: a prospec- perioperative, intravenous Flagyl as neck surgery. Arch Otolaryngol. 1984; tive, randomized, multicenter study. prophylaxis in elective colorectal resec- 110:224-7. Dis Colon Rectum. 1988; 31:774-7. tions. Surgery. 1985; 98:861-5. 496. Callender DL. Antibiotic prophylaxis 468. Blair J, McLeod R, Cohen Z et al. 482. Lewis RT. Oral versus systemic anti- in head and neck oncologic surgery: Ticarcillin/clavulanic acid (Timentin) biotic prophylaxis in elective colon the role of gram-negative coverage. Int compared to metronidazole/netilmicin surgery: a randomized study and meta- J Antimicrob Agents. 1999; 12(suppl in preventing postoperative infection analysis send a message from the 1990s. 1):s21-7. after elective colorectal surgery. Can J Can J Surg. 2002; 45:173-80. 497. Simo R, French G. The use of pro- Surg. 1987; 30:120-2. 483. Englesbe MJ, Brooks L, Kubus J et al. phylactic antibiotics in head and neck 469. Mendes Da Costa P, Kaufman L. Ami- A statewide assessment of surgical site oncological surgery. Curr Opin Otolar- kacin once daily plus metronidazole infection following colectomy: the role yngol Head Neck Surg. 2006; 14:55-61. versus amikacin twice daily plus met- of oral antibiotics. Ann Surg. 2010; 498. Lotfi CJ, Cavalcanti Rde C, Costa e ronidazole in colorectal surgery. Hepa- 252:514-20. Silva AM et al. Risk factors for surgical- togastroenterology. 1992; 39:350-4. 484. Kobayashi M, Mohri Y, Tonouchi H et site infections in head and neck cancer 470. Roland M. Prophylactic regimens in al. Randomized clinical trial compar- surgery. Otolaryngol Head Neck Surg. colorectal surgery: an open random- ing intravenous antimicrobial prophy- 2008; 138:74-80. ized consecutive trial of metronidazole laxis alone with oral and intravenous 499. Liu SA, Tung KC, Shiao JY et al. Pre- used alone or in combination with antimicrobial prophylaxis for the preliminary report of associated factors in ampicillin or doxycycline. World J Surg. vention of a surgical site infection in surgical site infection after major head 1986; 10:1003-8. colorectal cancer surgery. Surg Today. and neck neoplasm operations—does 471. Juul PZ, Klaaborg KE, Kronborg O. 2007; 37:383-8. the duration of prophylactic antibi- Single or multiple doses of metronida- 485. Wren SM, Ahmed N, Jamal A et otic matter? J Laryngol Otol. 2008; zole and ampicillin in elective colorec- al. Preoperative oral antibiotics in 122:403-8. tal surgery: a randomized trial. Dis colorectal surgery increase the rate of 500. Sepehr A, Santos BJ, Chou C et al. Anti- Colon Rectum. 1987; 30:526-8. Clostridium difficile colitis. Arch Surg. biotics in head and neck surgery in the 472. University of Melbourne Colorectal 2005; 140:752-6. setting of malnutrition, tracheotomy, Group. A comparison of single-dose 486. Krapohl GL, Phillips LR, Campbell and diabetes. Laryngoscope. 2009; Timentin with mezlocillin for prophy- DA et al. Bowel preparation for colec- 119:549-53. laxis of wound infection in elective tomy and risk of Clostridium difficile 501. Coskun H, Erisen L, Basut O. Factors colorectal surgery. Dis Colon Rectum. infection. Dis Colon Rectum. 2011; affecting wound infection rates in head 1989; 32:940-3. 54:810-7. and neck surgery. Otolaryngol Head 473. Stewart M, Taylor EW, Lindsay G. 487. Espin-Basany E, Sanchez-Garcia JL, Neck Surg. 2000; 123:328-33. Infection after colorectal surgery: Lopez-Cano M et al. Prospective, ran- 502. Robbins KT, Favrot S, Hanna D et al. a randomized trial of prophylaxis domised study on antibiotic prophy- Risk of surgical site infection in pa- with piperacillin versus sulbactam/ laxis in colorectal surgery. Is it really tients with head and neck cancer. Head piperacillin. J Hosp Infect. 1995; 29:135- necessary to use oral antibiotics? Int J Neck. 1990; 12:143-8. 42. Colorectal Dis. 2005; 20:542-6. 503. Tabet JC, Johnson JT. Wound infection 474. Bergman L, Solhaug JH. Single-dose 488. Sondheimer JM, Sokol RJ, Taylor S in head and neck surgery: prophylaxis, chemoprophylaxis in elective colorec- et al. Safety, efficacy, and tolerance of etiology and management. J Otolaryn- tal surgery. Ann Surg. 1987; 205:77-81. intestinal lavage in pediatric patients gol. 1990; 19:197-200. 475. Goransson G, Nilsson-Ehle I, Olsson undergoing diagnostic colonoscopy. 504. Girod DA, McCulloch TM, Tsue TT S et al. Single- versus multiple-dose J Pediatr. 1991; 119:148-52. et al. Risk factors for complications doxycycline prophylaxis in elective 489. Tuggle DW, Hoelzer DJ, Tunell WP et in clean-contaminated head and neck colorectal surgery. Acta Chir Scand. al. The safety and cost-effectiveness of surgical procedures. Head Neck. 1995; 1984; 150:245-9. polyethylene glycol electrolyte solu- 17:7-13. 476. Andaker L, Burman LG, Eklund A et al. tion bowel preparation in infants and 505. Miles BA, Potter JK, Ellis E III. The Fosfomycin/metronidazole compared children. J Pediatr Surg. 1987; 22:513-5. efficacy of postoperative antibiotic with doxycycline/metronidazole for 490. Weber RS, Callender DL. Antibi- regimens in the open treatment of the prophylaxis of infection after elec- otic prophylaxis in clean-contaminated mandibular fractures: a prospective tive colorectal surgery: a randomized, head and neck oncologic surgery. Ann randomized trial. J Oral Maxillofac double-blind, multi-centre trial in 517 Otol Rhinol Laryngol. 1992; 101:16-20. Surg. 2006; 64:576-82. patients. Eur J Surg. 1992; 158:181-5. 491. Avenia N, Sanguinetti A, Cirocchi R 506. Penel N, Fournier C, Roussel- 477. Sexton DJ. Carbapenems for surgi- et al. Antibiotic prophylaxis in thyroid Delvallez M et al. Prognostic sig- cal prophylaxis? N Engl J Med. 2006; surgery: a preliminary multicentric nificance of surgical site infections 355:2693-5. Italian experience. Ann Surg Innov Res. following major head and neck cancer 478. Condon RE, Bartlett J, Greenlee H et al. 2009; 3:10. surgery: an open non-comparative Efficacy of oral and systemic antibiotic 492. Johnson JT, Wagner RL. Infection fol- prospective study. Support Care Cancer. prophylaxis in colorectal operations. lowing uncontaminated head and neck 2004; 12:634-9. Arch Surg. 1983; 118:496-502. surgery. Arch Otolaryngol Head Neck 507. Lovato C, Wagner JD. Infection rates 479. Condon RE. Preoperative antibiotic Surg. 1987; 113:368-9. following perioperative prophylac- bowel preparation. Drug Ther.1983; 493. Saginur R, Odell PF, Poliquin JF. An- tic antibiotics versus postoperative 83:29-37. tibiotic prophylaxis in head and neck extended regimen prophylactic an- 480. Hinchey E, Richards G, Lewis R et al. cancer surgery. J Otolaryngol. 1988; tibiotics in surgical management of Moxalactam as single agent prophy- 17:78-80. mandibular fractures. J Oral Maxillofac laxis in the prevention of wound infec- 494. Mandell-Brown M, Johnson JT, Wagner Surg. 2009; 67:827-32. tion following colon surgery. Surgery. RL. Cost-effectiveness of prophylactic 508. Strauss M, Saccogna PW, Allphin 1987; 101:15-9. antibiotics in head and neck surgery. AL. Cephazolin and metronidazole 481. Jagelman DG, Fazio VW, Lavery IC et Otolaryngol Head Neck Surg. 1984; prophylaxis in head and neck surgery. al. A prospective, randomized, double- 92:520-3. J Laryngol Otol. 1997; 111:631-4.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 269 ASHP Report Antimicrobial prophylaxis

509. Simons JP, Johnson JT, Yu VL et al. otic treatment following tonsillec- 539. Rebuck JA, Murry KR, Rhoney DH The role of topical antibiotic prophy- tomy in children. J Laryngol Otol. 1996; et al. Infection related to intracranial laxis in patients undergoing contami- 110:357-9. pressure monitors in adults: analysis of nated head and neck surgery with flap 524. Caniello M, Passerotti GH, Goto EY et risk factor and antibiotic prophylaxis. reconstruction. Laryngoscope. 2001; al. Antibiotics in septoplasty: is it nec- J Neurol Neurosurg Psychiatry. 2000; 111:329-35. essary? Braz J Otorhinolaryngol. 2005; 69:381-4. 510. Johnson JT, Kachman K, Wagner 71:734-8. 540. Korinek AM, Baugnon T, Golmard JL RL et al. Comparison of ampicillin/ 525. Dhiwakar M, Eng CY, Selvaraj S et al. et al. Risk factors for adult nosocomial sulbactam versus clindamycin in the Antibiotics to improve recovery fol- meningitis after craniotomy: role of prevention of infection in patients un- lowing tonsillectomy: a systematic antibiotic prophylaxis. Neurosurgery. dergoing head and neck surgery. Head review. Otolaryngol Head Neck Surg. 2006; 58:126-33. Neck. 1997; 19:367-71. 2006; 134:357-64. 541. Lietard C, Thébaud V, Besson G et al. 511. Skitarelić N, Morović M, Manestar 526. Dhiwakar M, Clement WA, Supriya Risk factors for neurosurgical site D. Antibiotic prophylaxis in clean- M et al. Antibiotics to reduce post- infections: an 18-month prospective contaminated head and neck onco- tonsillectomy morbidity. Cochrane survey. J Neurosurg. 2008; 109:729- logical surgery. J Craniomaxillofac Surg. Database Syst Rev. 2008; 2:CD005607. 34. 2007; 35:15-20. 527. Fennessy BG, Harney M, O’Sullivan 542. Korinek AM, for the French Study 512. Andrews PJ, East CA, Jayaraj SM et al. MJ et al. Antimicrobial prophylaxis Group of Neurosurgical Infections Prophylactic vs. postoperative antibi- in otorhinolaryngology/head and SEHP C-CLIN Paris-Nord. Risk factors otic use in complex septorhinoplasty neck surgery. Clin Otolaryngol. 2007; for neurosurgical site infections after surgery: a prospective, randomized, 32:204-7. craniotomy: a prospective multicenter single-blind trial comparing efficacy. 528. Seven H, Sayin I, Turgut S. Antibiotic study of 2944 patients. Neurosurgery. Arch Facial Plast Surg. 2006; 8:84-7. prophylaxis in clean neck dissections. 1997; 41:1073-81. 513. Becker GD, Welch WD. Quantitative J Laryngol Otol. 2004; 118:213-6. 543. Korinek AM, Golmard JL, Elcheick A bacteriology of closed-suction wound 529. Slattery WH III, Stringer SP, Cassisi NJ. et al. Risk factors for neurosurgical site drainage in contaminated surgery. Prophylactic antibiotic use in clean, infections after craniotomy: a critical Laryngoscope. 1990; 100:403-6. uncontaminated neck dissection. reappraisal of antibiotic prophylaxis 514. Johnson JT, Yu VL. Role of aerobic Laryngoscope. 1995; 105:244-6. on 4578 patients. Br J Neurosurg. 2005; gram-negative rods, anaerobes, and 530. Weber RS, Raad I, Frankenthaler R et 19:155-62. fungi in surgical site infection after al. Ampicillin-sulbactam vs clindamy- 544. Valentini LG, Casali C, Chatenoud L head and neck surgery: implications cin in head and neck oncologic surgery. et al. Surgical site infections after elec- for antibiotic prophylaxis. Head Neck. The need for gram-negative coverage. tive neurosurgery: a survey of 1747 1989; 11:27-9. Arch Otolaryngol Head Neck Surg. patients. Neurosurgery. 2007; 61:88-96. 515. Rubin J, Johnson JT, Wagner RL et al. 1992; 118:1159-63. 545. Zabramski JM, Whiting D, Darouiche Bacteriologic analysis of surgical site 531. Johnson JT, Myers EN, Thearle PB RO et al. Efficacy of antimicrobial- infection following major head and et al. Antimicrobial prophylaxis for impregnated external ventricular drain neck surgery. Arch Otolaryngol Head contaminated head and neck surgery. catheters: a prospective, randomized Neck Surg. 1988; 114:969-72. Laryngoscope. 1984; 94:46-51. controlled trial. J Neurosurg. 2003; 516. Brown BM, Johnson JT, Wagner RL. 532. Righi M, Manfredi R, Farneti G et al. 98:725-30. Etiologic factors in head and neck Short-term versus long-term antimi- 546. Biyani N, Grisaru-Soen G, Steinbok P surgical site infections. Laryngoscope. crobial prophylaxis in oncologic head et al. Prophylactic antibiotics in pedi- 1987; 97:587-90. and neck surgery. Head Neck. 1996; atric shunt surgery. Childs Nerv Syst. 517. Penel N, Fournier C, Lefebvre D et al. 18:399-404. 2006; 22:1465-71. Multivariate analysis of risk factors 533. Rajan GP, Fergie N, Fischer U et al. An- 547. Holloway KL, Smith KW, Wilberger for surgical site infection in head and tibiotic prophylaxis in septorhinoplas- JE et al. Antibiotic prophylaxis during neck squamous cell carcinoma surgery ty? A prospective, randomized study. clean neurosurgery: a large, multi- with opening of mucosa. Study of 260 Plast Reconstr Surg. 2005; 116:1995-8. center study using cefuroxime. Clin surgical procedures. Oral Oncol. 2005; 534. Abubaker AO, Rollert MK. Post- Ther. 1996; 18:84-94. 41:294-303. operative antibiotic prophylaxis in 548. Whitby M, Johnson BC, Atkinson RL 518. Brook I. Microbiology and manage- mandibular fractures: a prelimi- et al. The comparative efficacy of intra- ment of post-surgical wounds infec- nary randomized, double-blind, and venous cefotaxime and trimethoprim/ tion in children. Pediatr Rehabil. 2002; placebo-controlled clinical study. sulfamethoxazole in preventing infec- 5:171-6. J Oral Maxillofac Surg. 2001; 59:1415-9. tion after neurosurgery: a prospective, 519. Brook I. Microbiology and principles 535. Avery CM, Ameerally P, Castling B randomized study. Br J Neurosurg. of antimicrobial therapy for head and et al. Infection of surgical wounds in 2000; 14:13-18. neck infections. Infect Dis Clin N Am. the maxillofacial region and free flap 549. Govender ST, Nathoo N, van Dellen 2007; 21:355-91. donor sites with methicillin-resistant JR. Evaluation of an antibiotic- 520. National Institute for Health and Clini- Staphylococcus aureus. Br J Oral Maxil- impregnated shunt system for the cal Excellence. Surgical site infection lofac Surg. 2006; 44:217-21. treatment of hydrocephalus. J Neuro- (clinical guideline 74) 2008. www.nice. 536. Gantz NM. Nosocomial central ner- surg. 2003; 99:831-9. org.uk/CG74 (accessed 2012 Dec 9). vous system infections. In: Mayhall 550. Tacconelli E, Cataldo MA, Albanese 521. Andreasen JO, Jensen SS, Schwartz O et CG, ed. Hospital epidemiology and A et al. Vancomycin versus cefazolin al. A systematic review of prophylactic infection control. 3rd ed. Philadelphia: prophylaxis for cerebrospinal shunt antibiotics in the surgical treatment of Lippincott Williams and Wilkins; 2004. placement in a hospital with a high maxillofacial fractures. J Oral Maxil- 537. Narotam PK, van Dellen JR, du Trevou prevalence of methicillin-resistant lofac Surg. 2006; 64:1664-8. MD et al. Operative sepsis in neurosur- Staphylococcus aureus. J Hosp Infect. 522. O’Reilly BJ, Black S, Fernandes J et al. Is gery: a method of classifying surgical 2008; 69:337-44. the routine use of antibiotics justified case. Neurosurgery. 1994; 34:409-16. 551. Wong GK, Poon WS, Lyon D et al. in adult tonsillectomy? J Laryngol Otol. 538. Kourbeti IS, Jacobs AV, Koslow M et al. Cefepime vs ampicillin/sulbactam and 2003; 117:382-5. Risk factors associated with postcrani- aztreonam as antibiotic prophylaxis in 523. Lee WC, Duignan MC, Walsh RM et otomy meningitis. Neurosurgery. 2007; neurosurgical patients with external al. An audit of prophylactic antibi- 60:317-26. ventricular drain: result of a prospec-

270 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

tive randomized controlled clinical results of a randomized, open study in 582. Walters BC, Goumnerova L, Hoffman trial. J Clin Pharm Ther. 2006; 31:231-5. 60 hydrocephalic patients. Surg Neurol. HJ et al. A randomized, controlled trial 552. Ragal BT, Browd SR, Schmidt RH. Sur- 1986; 24:178-80. of perioperative rifampin/trimethoprim gical shunt infection: significant reduc- 567. Blum J, Schwarz M, Voth D. Antibiotic in cerebrospinal fluid shunt surgery. tion when using intraventricular and single-dose prophylaxis of shunt infec- Childs Nerv Syst. 1992; 8:253-7. systemic antibiotic agents. J Neurosurg. tions. Neurosurg Rev. 1989; 12:239-44. 583. Martin JA, Hamilton BE, Sutton PD et 2006; 105:242-7. 568. Schmidt K, Gjerris F, Osgaard O et al. Births: final data for 2006.Natl Vital 553. Sarguna P, Lakshmi V. Ventriculoperi- al. Antibiotic prophylaxis in cerebro- Stat Rep. 2009; 57:1-104. toneal shunt infections. Indian J Med spinal fluid shunting: a prospective 584. Obstetric and medical complications. Microbiol. 2006; 24:52-4. randomized trial in 152 hydrocephalic In: American Academy of Pediatrics 554. Langley JM, Gravel D, Moore D et al. patients. Neurosurgery. 1985; 17:1-5. and American College of Obstetricians Study of cerebrospinal fluid shunt- 569. Griebel R, Khan M, Tan L. CSF shunt and Gynecologists. Guidelines for peri- associated infections in the first year complications: an analysis of con natal care. 6th ed. Elk Grove Village, following placement, by the Canadian tributory factors. Childs Nerv Syst. IL: American Academy of Pediatrics; Nosocomial Infection Surveillance 1985; 1:77-80. 2008:175-204. Program. Infect Control Hosp Epide- 570. Lambert M, MacKinnon AE, Vaishnav 585. Hofmeyr GJ, Smaill F. Antibiotic pro- miol. 2009; 30:285-8. A. Comparison of two methods of prophylaxis for cesarean section. Cochrane 555. Nisbet M, Briggs S, Ellis-Pegler R et phylaxis against CSF shunt infection. Database Syst Rev. 2002; 3:CD000933. al. Propionibacterium acnes: an under- Z Kinderchir. 1984; 39(suppl):109-10. 586. Killian C, Graffunder EM, Vinciguerra appreciated cause of post-neurosurgical 571. Zentner J, Gilsbach J, Felder T. Antibi- T et al. Risk factors for surgical-site infection. J Antimicrob Chemother. otic prophylaxis in cerebrospinal fluid infections following cesarean section. 2007; 60:1097-103. shunting: a prospective randomized Infect Control Hosp Epidemiol. 2001; 556. Conen A, Walti LN, Merlo A et al. trial in 129 patients. Neurosurg Rev. 22:613-7. Characteristics and treatment outcome 1995; 18:169-72. 587. Faro S. Infectious disease relations to of cerebrospinal fluid shunt-associated 572. Haines SJ, Walters BC. Antibiotic pro- cesarean section. Obstet Gynecol Clin infections in adults: a retrospective phylaxis for cerebrospinal fluid shunts: North Am. 1989; 16:363-71. analysis over an 11-year period. Clin a meta-analysis. Neurosurgery. 1994; 588. Olsen MA, Butler AM, Willers DM et Infect Dis. 2008; 47:73-82. 34:87-92. al. Risk factors for surgical site infec- 557. Barker FG II. Efficacy of prophylactic 573. Langley JM, LeBlanc JC, Drake J et al. tion after low transverse cesarean sec- antibiotics against meningitis after Efficacy of antimicrobial prophylaxis tion. Infect Control Hosp Epidemiol. craniotomy: a meta-analysis. Neurosur- in placement of cerebrospinal fluid 2008; 29:477-84. gery. 2007; 60:887-94. shunts: meta-analysis. Clin Infect Dis. 589. Hemsell DL. Infections after gyne- 558. Haines SJ, Goodman ML. Antibiotic 1993; 17:98-103. cologic surgery. Obstet Gynecol Clin prophylaxis of postoperative neuro- 574. Borowski A, Littleton AG, Borkhuu North Am. 1989; 16:381-400. surgical wound infection. J Neurosurg. B et al. Complications of intrathecal 590. Faro S. Antibiotic prophylaxis. Obstet 1982; 56:103-5. baclofen pump therapy in pediatric pa- Gynecol Clin North Am. 1989; 16:279- 559. Quartey GR, Polyzoidis K. Intraop tients. J Pediatr Orthop. 2010; 30:76-81. 89. erative antibiotic prophylaxis in neuro- 575. Motta F, Buonaguro V, Stignani C. 591. Tita AT, Rouse DJ, Blackwell S et al. surgery: a clinical study. Neurosurgery. The use of intrathecal baclofen pump Emerging concepts in antibiotic pro- 1981; 8:669-71. implants in children and adolescents: phylaxis for cesarean delivery: a sys- 560. Savitz MH, Katz SS. Prevention of pri- safety and complications in 200 con- tematic review. Obstet Gynecol. 2009; mary wound infection in neurosurgical secutive cases. J Neurosurg. 2007; 113:675-82. patients: a 10-year study. Neurosurgery. 107(suppl):32-5. 592. Chelmow D, Ruehli MS, Huang E. 1986; 18:685-8. 576. Fjelstad AB, Hommelstad J, Sorteberg Prophylactic use of antibiotics for 561. Blomstedt GC, Kytta J. Results of a A. Infections related to intrathecal nonlaboring patients undergoing ce- randomized trial of vancomycin pro- baclofen therapy in children and sarean delivery with intact membranes: phylaxis in craniotomy. J Neurosurg. adults: frequency and risk factors. a meta-analysis. Am J Obstet Gynecol. 1988; 69:216-20. J Neurosurg Pediatr. 2009; 4:487-93. 2001; 184:656-61. 562. Shapiro M, Wald U, Simchen E et al. 577. Follett KA, Boortz-Marx RL, Drake JM 593. Duff P, Smith PN, Keiser JF. Antibiotic Randomized clinical trial of intraop- et al. Prevention and management of prophylaxis in low-risk cesarean sec- erative antimicrobial prophylaxis of in- intrathecal drug delivery and spinal tion. J Reprod Med. 1982; 27:133-8. fection after neurosurgical procedures. cord stimulation system infections. 594. Apuzzio JJ, Reyelt C, Pelosi MA et al. J Hosp Infect. 1986; 8:283-95. Anesthesiology. 2004; 100:1582-94. Prophylactic antibiotics for cesarean 563. Watters WC 3rd, Baisden J, Bono CM 578. Ratilal BO, Costa J, Sampaio C. Antibi- section: comparison of high- and low- et al. Antibiotic prophylaxis in spine otic prophylaxis for surgical introduc- risk patients for endometritis. Obstet surgery: an evidence-based clinical tion of intracranial ventricular shunts. Gynecol. 1982; 59:693-8. guideline for the use of prophylactic Cochrane Database Syst Rev. 2006; 595. Duff P. Prophylactic antibiotics for ce- antibiotics in spine surgery. Spine J. 3:CD005365. sarean delivery: a simple cost-effective 2009; 9:142-6. 579. Arnaboldi L. Antimicrobial prophy- strategy for prevention of postop- 564. Wang EL, Prober CG, Hendrick BE. laxis with ceftriaxone in neurosurgical erative morbidity. Am J Obstet Gynecol. Prophylactic sulfamethoxazole and procedures: a prospective study of 100 1987; 157:794-8. trimethoprim in ventriculoperito- patients undergoing shunt operations. 596. Jakobi P, Weissman A, Sigler E et al. neal shunt surgery. A double-blind, Chemotherapy. 1996; 42:384-90. Post-cesarean section febrile morbid- randomized, placebo-controlled trial. 580. Alleyne CH, Hassan M, Zabramski JM. ity. Antibiotic prophylaxis in low-risk JAMA. 1984; 251:1174-7. The efficacy and cost of prophylactic patients. J Reprod Med. 1994; 39:707- 565. Blomstedt GC. Results in trimethoprim- and periprocedural antibiotics in pa- 10. sulfamethoxazole prophylaxis in ven- tients with external ventricular drains. 597. Rizk DE, Nsanze H, Mabrouk MH et al. triculostomy and shunting procedures. Neurosurgery. 2000; 47:1124-9. Systemic antibiotic prophylaxis in elec- J Neurosurg. 1985; 62:694-7. 581. Shurtleff DB, Stuntz JT, Hayden PW. tive cesarean delivery. Int J Gynaecol 566. Djindjian M, Fevrier MJ, Ottervbein Experience with 1201 cerebrospinal Obstet. 1998; 61:245-51. G et al. Oxacillin prophylaxis in cer fluid shunt procedures. Pediatr Neuro- 598. Rouzi AA, Khalifa F, Ba’aqeel H et al. ebrospinal fluid shunt procedures: sci. 1985-1986; 12:49-57. The routine use of cefazolin in cesar-

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 271 ASHP Report Antimicrobial prophylaxis

ean section. Int J Gynecol Obstet. 2000; uterine disease. Eur J Obstet Gynecol. II. Alterations of microbial flora. Am J 69:107-12. 2009; 148:172-6. Obstet Gynecol. 1976; 125:448-54. 599. Bagratee JS, Moodley J, Kleinschmidt I 612. Sokol AI, Green IC. Laparoscopic hys- 627. Appelbaum P, Moodley J, Chatterton S et al. A randomized controlled trial of terectomy. Clin Obstet Gynecol. 2009; et al. Metronidazole in the prophylaxis antibiotic prophylaxis in elective cae- 52:304-12. and treatment of anaerobic infection. S sarean delivery. Br J Obstet Gynaecol. 613. ACOG Committee Opinion No. 444: Afr Med J. 1978; 1:703-6. 2001; 108:143-8. choosing the route of hysterectomy for 628. Mittendorf R, Aronson MP, Berry RE 600. Hopkins L, Smaill F. Antibiotic prophy- benign disease. Obstet Gynecol. 2009; et al. Avoiding serious infections as- laxis regimens and drugs for cesarean 114:1156-8. sociated with abdominal hysterectomy: section. Cochrane Database Syst Rev. 614. Nieboer TE, Johnson N, Lethaby A et a meta-analysis of antibiotic pro- 1999; 2:CD001136. al. Surgical approach to hysterectomy phylaxis. Am J Obstet Gynecol. 1993; 601. Andrews WW, Hauth JC, Cliver SP for benign gynaecological disease. 169:1119-24. et al. Randomized clinical trial of Cochrane Database Syst Rev. 2009; 629. Duff P. Antibiotic prophylaxis for ab- extended spectrum antibiotic prophy- 3:CD003677. dominal hysterectomy. Obstet Gynecol. laxis with coverage for Ureaplasma 615. American College of Obstetricians 1982; 60:25-9. urealyticum to reduce post-cesarean and Gynecologists. ACOG Commit- 630. Miyazawa K, Hernandez E, Dillon MB. delivery endometritis. Obstet Gyncol. tee Opinion No. 388: supracervical Prophylactic topical cefamandole in 2003; 101:1183-9. hysterectomy. Obstet Gynecol. 2007; radical hysterectomy. Int J Gynaecol 602. Tita AT, Hauth JC, Grimes A et al. 110:1215-7. Obstet. 1987; 25:133-8. Decreasing incidence of postcesarean 616. Jennings RH. Prophylactic antibiotics 631. Micha JP, Kucera PR, Birkett JP et al. Pro- endometritis with extended-spectrum in vaginal and abdominal hysterec- phylactic mezlocillin in radical hyster- antibiotic prophylaxis. Obstet Gynecol. tomy. South Med J. 1978; 71:251-4. ectomy. Obstet Gynecol. 1987; 69:251-4. 2008; 111:51-6. 617. Hemsell D, Johnson ER, Hemsell PG 632. Sevin B, Ramos R, Lichtinger M et 603. Tita AT, Owen J, Stamm A et al. Impact et al. Cefazolin is inferior to cefotetan al. Antibiotic prevention of infec- of extended-spectrum antibiotic pro- as single-dose prophylaxis for women tion complicating radical abdominal phylaxis on incidence of postcesarean undergoing elective total abdominal hysterectomy. Obstet Gynecol. 1984; surgical wound infection. Am J Obstet hysterectomy. Clin Infect Dis. 1995; 64:539-45. Gynecol. 2008; 199:303.e1-e3. 20:677-84. 633. Rosenshein NB, Ruth JC, Villar J et al. 604. Meyer NL, Hosier KV, Scott K et al. 618. Goosenberg J, Emich JP Jr, Schwarz A prospective randomized study of Cefazolin versus cefazolin plus metro- RH. Prophylactic antibiotics in vaginal doxycycline as a prophylactic antibiotic nidazole for antibiotic prophylaxis at hysterectomy. Am J Obstet Gynecol. in patients undergoing radical hyster- cesarean section. South Med J. 2003; 1969; 105:503-6. ectomy. Gynecol Oncol. 1983; 15:201-6. 96:992-5. 619. Marsden DE, Cavanagh D, Wisniewski 634. Zakashansky K, Bradley WH, Nezhat 605. Costantine MM, Rahman M, Ghulmiyah BJ et al. Factors affecting the incidence FR. New techniques in radical hysterec- L et al. Timing of perioperative antibiot- of infectious morbidity after radical tomy. Curr Opin Obstet Gynecol. 2008; ics for cesarean delivery: a metaanaly- hysterectomy. Am J Obstet Gynecol. 20:14-9. sis. Am J Obstet Gynecol. 2008; 199:301. 1985; 152:817-21. 635. Hemsell D, Menon M, Friedman A. e1-e6. 620. Mann W, Orr J, Shingleton H et al. Ceftriaxone or cefazolin prophylaxis 606. Sullivan SA, Smith T, Chang E et al. Perioperative influences on infectious for the prevention of infection after Administration of cefazolin prior to morbidity in radical hysterectomy. Gy- vaginal hysterectomy. Am J Surg. 1984; skin incision is superior to cefazolin necol Oncol. 1981; 11:207-12. 148:22-6. at cord clamping in preventing post- 621. Löfgren M, Poromaa IS, Stjerndahl 636. Hemsell DL, Johnson ER, Bawdon RE cesarean infectious morbidity: a ran- JH et al. Postoperative infections and et al. Ceftriaxone and cefazolin pro- domized, controlled trial. Am J Obstet antibiotic prophylaxis for hysterec- phylaxis for hysterectomy. Surg Gynecol Gynecol. 2007; 196:455.e1-e5. tomy in Sweden: a study by the Swed- Obstet. 1985; 161:197-203. 607. Committee Opinion No. 465: antimi- ish National Register for Gynecologic 637. Soper D, Yarwood R. Single-dose crobial prophylaxis for cesarean deliv- Surgery. Acta Obstet Gynecol Scand. antibiotic prophylaxis in women un- ery: timing of administration. Obstet 2004; 83:1202-7. dergoing vaginal hysterectomy. Obstet Gynecol. 2010; 116:791-2. 622. Olsen MA, Higham-Kessler J, Yokoe DS Gynecol. 1987; 53:879-82. 608. Witt A, Döner M, Petricevic L et al. An- et al. Developing a risk stratification 638. Rapp RP, Connors E, Hager WD et al. tibiotic prophylaxis before surgery vs model for surgical site infection after Comparison of single-dose moxalac- after cord clamping in elective cesarean abdominal hysterectomy. Infect Control tam and a three-dose regimen of cef delivery: a double-blind, prospective, Hosp Epidemiol. 2009; 30:1077-83. oxitin for prophylaxis in vaginal hys- randomized, placebo-controlled trial. 623. Soper DE, Bump RC, Hurt GW. terectomy. Clin Pharm. 1986; 5:988-93. Arch Surg. 2011; 146:1404-9. Wound infection after abdominal hys- 639. Roy S, Wilkins J. Single-dose cefotax 609. Whiteman MK, Hillis SD, Jamieson DJ terectomy: effect of the depth of sub- ime versus 3- to 5-dose cefoxitin for et al. Inpatient hysterectomy surveil- cutaneous tissue. Am J Obstet Gynecol. prophylaxis of vaginal or abdominal lance in the United States, 2000-2004. 1995; 173:465-71. hysterectomy. J Antimicrob Chemother. Am J Obstet Gynecol. 2008; 198:34. 624. Soper DE. Infections of the female pel- 1984; 14(suppl B):217-21. e1-e7. vis. In: Mandell GL, Bennett JE, Dolin 640. Roy S, Wilkins J, Hemsell DL et al. 610. Schorge JO, Schaffer JI, Halvorson R, eds. Mandell, Douglas and Bennett’s Efficacy and safety of single-dose LM et al. Surgeries for benign gyneco principles and practice of infectious ceftizoxime vs. multiple-dose cefoxitin logic conditions. Chap. 41. In: Schorge diseases. 7th ed. New York: Churchill in preventing infection after vaginal JO, Schaffer JI, Halvorson LM et al., Livingstone; 2009:1514-6. hysterectomy. J Reprod Med. 1988; eds. Williams gynecology. New York: 625. Ohm MJ, Galask RP. The effect of 33(suppl 1):149-53. McGraw-Hill Professional; 2008. antibiotic prophylaxis on patients un- 641. Roy S, Wilkins J, Galaif E et al. Compar- 611. Drahonovsky J, Haakova L, Otcenasek dergoing vaginal operations. II. Altera- ative efficacy and safety of cefmetazole M et al. A prospective randomized tions of microbial flora.Am J Obstet or cefoxitin in the prevention of comparison of vaginal hysterectomy, Gynecol. 1975; 123:597-604. postoperative infection following laparoscopically assisted vaginal hys- 626. Ohm MJ, Galask RP. The effect of an- vaginal and abdominal hysterectomy. terectomy, and total laparoscopic tibiotic prophylaxis on patients under- J Antimicrob Chemother. 1989; 23 hysterectomy in women with benign going total abdominal hysterectomy. (suppl D):109-17.

272 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

642. Mercer LJ, Murphy HJ, Ismail MA 655. Lett WJ, Ansbacher R, Davison BL et 670. Garat M, Moser CL, Martín-Baranera et al. A comparison of cefonicid and al. Prophylactic antibiotics for women M et al. Prophylactic intracameral cefoxitin for preventing infections after undergoing vaginal hysterectomy. cefazolin after cataract surgery: endo- vaginal hysterectomy. J Reprod Med. J Reprod Med. 1977; 19:51-4. phthalmitis risk reduction and safety 1988; 33:223-6. 656. Hamod KA, Spence MR, Roshenshein results in a 6-year study. J Cataract 643. Hemsell DL, Heard ML, Nobles BJ et NB et al. Single and multidose prophy- Refract Surg. 2009; 35:637-42. al. Single-dose cefoxitin prophylaxis laxis in vaginal hysterectomy: a com- 671. Jensen MK, Fiscella RG, Moshirfar M for premenopausal women undergoing parison of sodium cephalothin and et al. Third- and fourth-generation vaginal hysterectomy. Obstet Gynecol. metronidazole. Am J Obstet Gynecol. fluoroquinolones: retrospective com- 1984; 63:285-90. 1980; 136:976-9. parison of endophthalmitis after cata- 644. McGregor JA, Phillips LE, Dunne JT 657. Hemsell DL, Johnson ER, Heard MC et ract surgery performed over 10 years. et al. Results of a double-blind, pla- al. Single dose piperacillin versus triple J Cataract Refract Surg. 2008; 34:1460- cebo controlled clinical trial program dose cefoxitin prophylaxis at vaginal 7. of single-dose ceftizoxime versus and abdominal hysterectomy. South 672. Mollan SP, Mollan AJ, Konstantinos multiple-dose cefoxitin as prophylaxis Med J. 1989; 82:438-42. C et al. Incidence of endophthalmitis for patients undergoing vaginal and 658. Turano A. New clinical data on the following vitreoretinal surgery. Int abdominal hysterectomy. J Am Coll prophylaxis of infections in abdominal, Ophthalmol. 2009; 29:203-5. Surg. 1994; 178:12-31. gynecologic, and urologic surgery. Am 673. Moshirfar M, Feiz V, Vitale AT et al. 645. Orr JW Jr, Varner RE, Kilgore LC et J Surg. 1992; 164(suppl):16S-20S. Endophthalmitis after uncompli- al. Cefotetan versus cefoxitin as pro- 659. D’Addato F, Canestrelli M, Repinto cated cataract surgery with the use of phylaxis in hysterectomy. Am J Obstet A et al. Perioperative prophylaxis in fourth-generation fluoroquinolones: a Gynecol. 1986; 154:960-3. abdominal and vaginal hysterectomy. retrospective observational case series. 646. Orr JW Jr, Sisson PF, Barrett JM et al. Clin Exp Obstet Gynecol. 1993; 20:95- Ophthalmology. 2007; 114:686-91. Single center study results of cefotetan 101. 674. Romero P, Méndez I, Salvat M et al. and cefoxitin prophylaxis for ab 660. Gonen R, Hakin M, Samberg I et al. Intracameral cefazolin as prophylaxis dominal or vaginal hysterectomy. Am J Short-term prophylactic antibiotic for against endophthalmitis in cataract Obstet. 1988; 158(3 pt 2):714-6. elective abdominal hysterectomy: how surgery. J Cataract Refract Surg. 2006; 647. Berkeley AS, Orr JW, Cavanagh D et al. short? Eur J Obstet Gynecol Reprod Biol. 32:438-41. Comparative effectiveness and safety of 1985; 20:229-34. 675. Soto AM, Mendívil MP. The effect of cefotetan and cefoxitin as prophylactic 661. Scarpignato C, Labruna C, Condemi V topical povidone-iodine, intraocular agents in patients undergoing abdomi- et al. Comparative efficacy of two dif- vancomycin, or both on aqueous nal or vaginal hysterectomy. Am J Surg. ferent regimens of antibiotic prophy- humor cultures at the time of cata- 1988; 155:81-5. laxis in total abdominal hysterectomy. ract surgery. Am J Ophthalmol. 2001; 648. Berkeley AS, Freedman KS, Ledger WJ Pharmatherapeutica. 1980; 2:450-5. 131:293-300. et al. Comparison of cefotetan and 662. Hemsell DL, Hemsell PG, Heard ML 676. Taban M, Behrens A, Newcomb RL et cefoxitin prophylaxis for abdominal et al. Preoperative cefoxitin prophy- al. Incidence of acute endophthalmitis and vaginal hysterectomy. Am J Obstet laxis for elective abdominal hyster- following penetrating keratoplasty. Gynecol. 1988; 158:706-9. ectomy. Am J Obstet Gynecol. 1985; Arch Ophthalmol. 2005; 123:605-9. 649. Gordon SF. Results of a single center 153:225-6. 677. Wejde G, Samolov B, Seregard S et al. study of cefotetan prophylaxis in 663. Triolo O, Mancuso A, Pantano F. Risk factors for endophthalmitis fol- abdominal or vaginal hysterectomy. Amoxycillin/clavulanate prophylaxis lowing cataract surgery: a retrospective Am J Obstet Gynecol. 1988; 158:710-4. in gynecologic surgery. Int J Gynaecol case-control study. J Hosp Infect. 2005; [Erratum, Am J Obstet Gynecol. 1989; Obstet. 2004; 85:59-61. 61:251-6. 160:1025.] 664. Su HY, Ding DC, Chen DC et al. Pro- 678. Wu PC, Li M, Chang SJ et al. Risk of 650. Campillo F, Rubio JM. Comparative spective randomized comparison of endophthalmitis after cataract surgery study of single-dose cefotaxime and single-dose versus 1-day cefazolin for using different protocols for povidone- multiple doses of cefoxitin and cefazo- prophylaxis in gynecologic surgery. iodine preoperative disinfection. J Ocul lin as prophylaxis in gynecologic sur- Acta Obstet Gynecol Scand. 2005; Pharmacol Ther. 2006; 22:54-61. gery. Am J Surg. 1992; 164(suppl):12S- 84:384-9. 679. Barry P, Seal DV, Gettinby G et al. 15S. 665. Tchabo JG, Cutting ME, Butler C. Pro- ESCRS study of prophylaxis of postop- 651. Berkeley AS, Haywork SD, Hirsch JC phylactic antibiotics in patients under- erative endophthalmitis after cataract et al. Controlled, comparative study of going total vaginal or abdominal hys- surgery: preliminary report of prin- moxalactam and cefazolin for prophy- terectomy. Int Surg. 1985; 70:349-52. cipal results from a European multi- laxis of abdominal hysterectomy. Surg 666. Read RW. Endophthalmitis. In: Yanoff center study. J Cataract Refract Surg. Gynecol Obstet. 1985; 161:457-61. M, Duker JS, eds. Ophthalmology. 3rd 2006; 32:407-10. 652. Tuomala RE, Fischer SG, Munoz A et ed. St. Louis: Mosby; 2009. 680. ESCRS Endophthalmitis Study Group. al. A comparative trial of cefazolin and 667. Bucci FA, Amico LM, Evans RE. Anti- Prophylaxis of postoperative endo- moxalactam as prophylaxis for prevent- microbial efficacy of prophylactic gati- phthalmitis following cataract surgery: ing infection after abdominal hysterec- floxacin 0.3% and moxifloxacin 0.5% results of the ESCRS multicenter study tomy. Obstet Gynecol. 1985; 66:372-6. in patients undergoing phacoemulsifi- and identification of risk factors. 653. Chongsomchai C, Lumbiganon cation surgery. Eye Contact Lens. 2008; J Cataract Refract Surg. 2007; 33:978-88. P, Thinkhamrop J et al. Placebo- 34:39-42. 681. Kamalarajah S, Ling R, Silvestri G et al. controlled, double-blind, random- 668. Colleaux KM, Hamilton WK. Effect of Presumed infectious endophthalmitis ized study of prophylactic antibiotics prophylactic antibiotics and incision following cataract surgery in the UK: a in elective abdominal hysterectomy. type on the incidence of endophthal- case-control study of risk factors. Eye. J Hosp Infect. 2002; 52:302-6. mitis after cataract surgery. Can J Oph- 2007; 21:580-6. 654. Cormio G, Di Fazio F, Lorusso F et al. thalmol. 2000; 35:373-8. 682. Montan PG, Setterquist H, Marcusson Antimicrobial prophylaxis in laparo- 669. Eifrig CW, Flynn HW Jr, Scott IU et al. E et al. Preoperative gentamicin eye tomic gynecologic surgery: a prospec- Acute-onset postoperative endophthal- drops and chlorhexidine solution in tive randomized study comparing mitis: review of incidence and visual cataract surgery: experimental and amoxicillin-clavulanic acid with ce- outcomes (1995–2001). Ophthalmic clinical results. Eur J Ophthalmol. 2000; fazolin. J Chemother. 2002; 14:618-22. Surg Lasers. 2002; 33:373-8. 10:286-92.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 273 ASHP Report Antimicrobial prophylaxis

683. Recchia FM, Busbee BG, Pearlman RB of the ESCRS endophthalmitis study. 709. Holland EJ, McCarthy M, Holland S. et al. Changing trends in the micro- J Cataract Refract Surg. 2009; 35:770-3. The ocular penetration of levofloxacin biologic aspects of postcataract endo- 696. O’Brien TP, Arshinoff SA, Mah FS. 1.5% and gatifloxacin 0.3% ophthal- phthalmitis. Arch Ophthalmol. 2005; Perspective on antibiotics for postop- mic solutions in subjects undergoing 123:341-6. erative endophthalmitis prophylaxis: corneal transplant surgery. Curr Med 684. American Academy of Ophthalmology. potential role of moxifloxacin.J Cata- Res Opin. 2007; 23:2955-60. Cataract in the adult eye, preferred ract Refract Surg. 2007; 33:1790-800. 710. Costello P, Bakri SJ, Beer PM et al. Vit- practice pattern. http://one.aao.org/ 697. Chang DF, Braga-Mele R, Mamalis reous penetration of topical moxifloxa- CE/PracticeGuidelines/PPP_Content. N et al. Prophylaxis of postoperative cin and gatifloxacin in humans.Retina. aspx?cid=a80a87ce-9042-4677-85d7- endophthalmitis after cataract surgery: 2006; 26:191-5. 4b876deed276 (accessed 2012 Dec 9). results of the 2007 ASCRS member 711. Burka JM, Bower KS, Vanroekel RC 685. Hatch WV, Cernat G, Wong D et al. survey. J Cataract Refract Surg. 2007; et al. The effect of fourth-generation Risk factors for acute endophthalmitis 33:1801-5. fluoroquinolones gatifloxacin and after cataract surgery: a population- 698. De Kaspar HM, Kreutzer TC, Aguirre- moxifloxacin on epithelial healing fol- based study. Ophthalmology. 2009; Romo I et al. A prospective random- lowing photorefractive keratectomy. 116:425-40. ized study to determine the efficacy Am J Ophthalmol. 2005; 140:83-7. 686. Lertsumitkul S, Myers PC, O’Rourke of preoperative topical levofloxacin in 712. Durrie DS, Trattler W. A comparison of MT et al. Endophthalmitis in the reducing conjunctival bacterial flora. therapeutic regimens containing moxi- western Sydney region: a case-control Am J Ophthalmol. 2008; 145:136-42. floxacin 0.5% ophthalmic solution and study. Clin Experiment Ophthalmol. 699. Montan PG, Wejde G, Setterquist H et gatifloxacin 0.3% ophthalmic solution 2001; 29:400-5. al. Prophylactic intracameral cefurox- for surgical prophylaxis in patients 687. De Kaspar HM, Chang RT, Singh K ime: evaluation of safety and kinetics undergoing LASIK or LASEK. J Ocul et al. Prospective randomized com- in cataract surgery. J Cataract Refract Pharmacol Ther. 2005; 21:236-41. parison of 2 different methods of 5% Surg. 2002; 28:982-7. 713. Campos M, Ávila M, Wallau A et al. povidone-iodine applications for ante- 700. Chisari G, Cavallaro G, Reibaldi M et Efficacy and tolerability of a fixed-dose rior segment intraocular surgery. Arch al. Presurgical antimicrobial prophy- moxifloxacin-dexamethasone formu- Ophthalmol. 2005; 123:161-5. laxis: effect on ocular flora in healthy lation for topical prophylaxis in LASIK: 688. Ta CN, Egbert PR, Singh K et al. patients. Int J Clin Pharmacol Ther. a comparative, double-masked clinical Prospective randomized comparison 2004; 42:35-8. trial. Clin Ophthalmol. 2008; 2:331-8. of 3-day versus 1-hour preoperative 701. Park SH, Lim JA, Choi JS et al. The 714. Freitas LL, Soriano E, Muccioli C et al. ofloxacin prophylaxis for cataract sur- resistance patterns of normal ocular Efficacy and tolerability of a combined gery. Ophthalmology. 2002; 109:2036- bacterial flora to 4 fluoroquinolone moxifloxacin/dexamethasone formula- 41. antibiotics. Cornea. 2009; 28:68-72. tion for topical prophylaxis and reduc- 689. Fernández-Rubio E, Urcelay JL, Cuesta- 702. Ciulla TA, Starr MB, Masket S. Bacte- tion of inflammation in phacoemulsi- Rodriguez T. The antibiotic resistance rial endophthalmitis prophylaxis for fication: a comparative, double masked pattern of conjunctival bacteria: a key cataract surgery: an evidence-based clinical trial. Curr Med Res Opin. 2007; for designing a cataract surgery pro- update. Ophthalmology. 2002; 109:13- 23:3123-30. phylaxis. Eye. 2009; 23:1321-8. 26. 715. Lane SS, Osher RH, Masket S et al. 690. Gelfand YA, Mezer E, Linn S et al. Lack 703. Gordon-Bennett P, Karas A, Flanagan Evaluation of the safety of prophylactic of effect of prophylactic gentamicin D et al. A survey of measures used intracameral moxifloxacin in cataract treatment on intraocular and extra- for the prevention of postoperative surgery. J Cataract Refract Surg. 2008; ocular fluid cultures after pars plana endophthalmitis after cataract surgery 34:1451-9. vitrectomy. Ophthalmic Surg Lasers. in the United Kingdom. Eye. 2008; 716. Espiritu CR, Caparas VL, Bolinao 1998; 29:497-501. 22:620-7. JG. Safety of prophylactic intracam- 691. Vasavada AR, Gajjar D, Raj SM et 704. Ta CN, Singh K, Egbert PR et al. Pro- eral moxifloxacin 0.5% ophthalmic al. Comparison of 2 moxifloxacin spective comparative evaluation of solution in cataract surgery patients. regimens for preoperative prophylaxis: povidone-iodine (10% for 5 minutes J Cataract Refract Surg. 2007; 33:63-8. prospective randomized triple-masked versus 5% for 1 minute) as prophylaxis 717. Olson RJ. Reducing the risk of postop- trial. Part 2: residual conjunctival for ophthalmic surgery. J Cataract Re- erative endophthalmitis. Surv Ophthal- flora. J Cataract Refract Surg. 2008; fract Surg. 2008; 34:171-2. mol. 2004; 49(suppl 2):s55-61. 34:1383-8. 705. Cahane M, Ben Simon GJ, Barequet 718. Yu-Wai-Man P, Morgan SJ, Hildreth 692. Osher RH, Amdahl LD, Cheetham IS et al. Human corneal stromal tissue AJ et al. Efficacy of intracameral and JK. Antimicrobial efficacy and aque- concentration after consecutive doses subconjunctival cefuroxime in pre- ous humor concentration of pre- of topically applied 3.3% vancomycin. venting endophthalmitis after cataract operative and postoperative topical Br J Ophthalmol. 2004; 88:22-4. surgery. J Cataract Refract Surg. 2008; trimethoprim/polymyxin B sulfate 706. Bucci FA. An in vivo study comparing 34:447-51. versus tobramycin. J Cataract Refract the ocular absorption of levofloxacin 719. Vasavada AR, Gajjar D, Raj SM et Surg. 1994; 20:3-8. and ciprofloxacin prior to phacoemul- al. Comparison of 2 moxifloxacin 693. Barequet IS, Jabbur NS, Barron Y et al. sification. Am J Ophthalmol. 2004; regimens for preoperative prophylaxis: Perioperative microbiologic profile 137:308-12. prospective randomized triple-masked of the conjunctiva in photoreactive 707. García-Sáenz MC, Arias-Puente A, trial. Part 1: aqueous concentration of keratectomy. J Refract Surg. 2001; Fresnadillo-Martinez MJ et al. Hu- moxifloxacin. J Cataract Refract Surg. 17:55-62. man aqueous humor levels of oral 2008; 34:1379-82. 694. Seal DV, Barry P, Gettinby G et al. ciprofloxacin, levofloxacin and moxi- 720. Eron LJ. Prevention of infection fol- ESCRS study of prophylaxis of postop- floxacin. J Cataract Refract Surg. 2001; lowing orthopedic surgery. Antibiot erative endophthalmitis after cataract 27:11969-74. Chemother. 1985; 33:140-64. surgery: case for a European multi- 708. Hariprasad SM, Blinder KJ, Shah GK 721. Gosselin RA, Roberts I, Gillespie WJ. center study. J Cataract Refract Surg. et al. Penetration pharmacokinetics Antibiotics for preventing infection in 2006; 32:396-406. of topically administered 0.5% moxi- open limb fractures. Cochrane Data- 695. Gore DM, Anjunawela RI, Little BC. floxacin ophthalmic solution in human base Syst Rev. 2004; 1:CD003764. United Kingdom survey of antibiotic aqueous and vitreous. Arch Ophthal- 722. Hauser CJ, Adams CA Jr, Eachempati SR prophylaxis practice after publication mol. 2005; 123:39-44. et al. Surgical Infection Society guide-

274 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

line: prophylactic antibiotic use in pedic surgery. J Bone Joint Surg. 1974; 754. Rao N, Cannella B, Crossett LS et al. A open fractures: an evidence-based 56:777-82. preoperative decolonization protocol guideline. Surg Infect. 2006; 7:379-405. 739. Boxma H, Broekhuizen T, Patka P for Staphylococcus aureus prevents or- 723. Jaeger M, Maier D, Kern WV et al. et al. Randomised controlled trial of thopaedic infections. Clin Orthop Relat Antibiotics in trauma and orthope- single-dose antibiotic prophylaxis in Res. 2008; 466:1343-8. dic surgery—a primer of evidence- surgical treatment of closed fractures: 755. Kim DH, Spencer M, Davidson SM et based recommendations. Injury. 2006; the Dutch Trauma Trial. Lancet. 1996; al. Institutional prescreening for detec- 37:s74-80. 347:1133-7. tion and eradication of methicillin- 724. Luchette FA, Bone LB, Born CT et al. 740. Weinstein MA, McCabe JP, Cammisa resistant Staphylococcus aureus in pa- Practice management guidelines for FP Jr. Postoperative spinal wound in- tients undergoing elective orthopaedic prophylactic antibiotic use in open fection: a review of 2,391 consecutive surgery. J Bone Joint Surg Am. 2010; fractures. www.east.org/tpg/openfrac. index procedures. J Spinal Disord. 92:1820-6. pdf (accessed 2008 May 26). 2000; 13:422-6. 756. Zgonis T, Jolly GP, Garbalosa JC. The 725. Whitehouse JD, Friedman ND, Kirkland 741. Trampuz A, Zimmerli W. Antimicro- efficacy of prophylactic intravenous KB et al. The impact of surgical-site bial agents in orthopedic surgery: pro- antibiotics in elective foot and ankle infections following orthopedic sur- phylaxis and treatment. Drugs. 2006; surgery. J Foot Ankle Surg. 2004; 43:97- gery at a community hospital and 66:1089-105. 103. university hospital: adverse quality of 742. Yamaguchi K, Adams RA, Morrey BF. 757. Kurzweil PR. Antibiotic prophylaxis life, excess length of stay and extra cost. Infection after total elbow arthro- for arthroscopic surgery. Arthroscopy. Infect Control Hosp Epidemiol. 2002; plasty. J Bone Joint Surg Am. 1998; 2006; 22:452-4. 23:183-9. 80:481-91. 758. Wieck JA, Jackson JK, O’Brien TJ et 726. Boyd RJ, Burke JF, Colton T. A double- 743. Bohsali KI, Wirth MA, Rockwood CA al. Efficacy of prophylactic antibiotics blind clinical trial of prophylactic Jr. Complications of total shoulder ar- in arthroscopic surgery. Orthopedics. antibiotics in hip fractures. J Bone Joint throplasty. J Bone Joint Surg Am. 2006; 1997; 20:133-4. Surg. 1973; 55:1251-8. 88:2279-92. 759. Bert JM, Giannini D, Nace L. Antibi- 727. Sculco TP. The economic impact of in- 744. Meehan J, Jamali AA, Nguyen H. Pro- otic prophylaxis for arthroscopy of the fected joint arthroplasty. Orthopaedics. phylactic antibiotics in hip and knee knee: is it necessary? Arthroscopy. 2007; 1995; 18:871-3. arthroplasty. J Bone Joint Surg Am. 23:4-6. 728. Kurtz SM, Lau E, Schmier J et al. 2009; 91:2480-90. 760. Babcock HM, Carroll C, Matava M Infection burden for hip and knee 745. Costerton JW, Stewart PS, Greenberg et al. Surgical site infections after ar- arthroplasty in the United States. J Ar- EP. Bacterial biofilms: a common cause throscopy: outbreak investigation and throplasty. 2008; 23:984-91. of persistent infections. Science. 1999; case control study. Arthroscopy. 2003; 729. Bozic KJ, Ries MD. The impact of 284:1318-22. 19:172-81. infection after total hip arthroplasty 746. Costerton JW. Biofilm theory can guide 761. Olix ML, Klug TJ, Coleman CR et al. on hospital and surgeon resource the treatment of device-related ortho- Prophylactic antibiotics in elective op- utilization. J Bone Joint Surg Am. 2005; paedic infections. Clin Orthop Related erations on bones, joints, and tendons. 87:1746-51. Res. 2005; 437:7-11. Surg Forum. 1960; 10:818-9. 730. Hebert CK, Williams RE, Levy RS et al. 747. Lewis K. Riddle of biofilm resistance. 762. Tachdjian MO, Compere EL. Postop- Cost of treating an infected total knee Antimicrob Agents Chemother. 2001; erative wound infections in orthopedic replacement. Clin Orthop Related Res. 45:999-1007. surgery: evaluation and prophylactic 1996; 331:140-5. 748. Matthews PC, Berendt AR, McNally antibiotics. J Int Coll Surg. 1957; 731. Anderson DJ, Kaye KS, Schmader KE et MA et al. Diagnosis and management 28:797-805. al. Clinical and financial outcomes due of prosthetic joint infection. BMJ. 763. Beiner JM, Grauer J, Kwon BK et al. to methicillin resistant Staphylococcus 2009; 338:1378-83. Postoperative wound infections of the aureus surgical site infection: a multi- 749. Prokuski L. Prophylactic antibiotics in spine. Neurosurg Focus. 2003; 15:1-5. center matched outcomes study. PLoS orthopaedic surgery. J Am Acad Orthop 764. Labbé AC, Demers AM, Rodrigues R One. 2009; 4:e8305. Surg. 2008; 16:283-93. et al. Surgical-site infection following 732. Brown EM, Path FR, Pople IK et al. 750. Gernaat-Van Der Sluis AJ, spinal fusion: a case-control study in Prevention of postoperative infection Hoogenboom-Verdegaal AM, Edixhoven a children’s hospital. J Infect Control in patients undergoing spinal surgery. PJ et al. Prophylactic mupirocin could Hosp Epidemiol. 2003; 24:591-5. Spine. 2004; 29:938-45. reduce orthopedic wound infections: 765. Lonstein J, Winter R, Moe J et al. 733. Barker FG II. Efficacy of prophylactic 1044 patients treated with mupirocin Wound infection with Harrington antibiotic therapy in spinal surgery: compared with 1260 historical con- instrumentation and spine fusion for a meta-analysis. Neurosurgery. 2002; trols. Acta Orthop Scand. 1998; 69: scoliosis. Clin Orthop Relat Res. 1973; 51:391-401. 412-4. 96:222-33. 734. Ericson C, Lidgren L, Lindberg L. 751. Wilcox MH, Hall J, Pike H et al. Use 766. Dimick JB, Lipsett PA, Kostuik JP. Spine Cloxacillin in the prophylaxis of post- of perioperative mupirocin to prevent update: antimicrobial prophylaxis in operative infections of the hip. J Bone methicillin resistant Staphylococcus spine surgery: basic principles and re- Joint Surg. 1973; 55:808-13 . aureus (MRSA) orthopedic surgical cent advances. Spine. 2000; 25:2544-8. 735. Pollard JP, Hughes SP, Scott JE et al. site infections. J Hosp Infect. 2003; 767. Kanafani ZA, Dakdouki GK, El- Antibiotic prophylaxis in total hip 54:196-201. Dbouni O et al. Surgical site infections replacement. Br Med J. 1979; 1:707-9. 752. Coskun D, Aytac J. Decrease in Staphy- following spinal surgery at a tertiary 736. Burnett JW, Gustilo RB, Williams lococcus aureus surgical-site infection care center in Lebanon: incidence, mi- DN et al. Prophylactic antibiotics in rates after orthopaedic surgery after crobiology, and risk factors. Scand J hip fractures. J Bone Joint Surg. 1980; intranasal mupirocin ointment. J Hosp Infect Dis. 2006; 38:589-92. 62:457-62. Infect. 2004; 58:90-1. 768. O’Toole JE, Eichholz KM, Fessler RG. 737. Tengve B, Kjellander J. Antibiotic pro- 753. Van Rijen MM, Bonten M, Wenzel RP Surgical site infection rates after mini- phylaxis in operations on trochanteric et al. Intranasal mupirocin for reduc- mally invasive spinal surgery. J Neuro- femoral fractures. J Bone Joint Surg. tion of Staphylococcus aureus infec- surg Spine. 2009; 11:471-6. 1978; 60:97-9. tions in surgical patients with nasal 769. Hellbusch LC, Helzer-Julin M, Doran 738. Pavel A, Smith RL, Ballard A et al. carriage: a systematic review. J Antimi- SE et al. Single-dose vs multiple-dose Prophylactic antibiotics in clean ortho- crob Chemother. 2008; 61:254-61. antibiotic prophylaxis in instrumented

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 275 ASHP Report Antimicrobial prophylaxis

lumbar fusion—a prospective study. and Mortality Committee. Spine. 2010; 801. AlBuhairan B, Hind D, Hutchinson Surg Neurol. 2008; 70:622-7. 35:99-103. A. Antibiotic prophylaxis for wound 770. Pull Ter Gunne AF, van Laarhoven 785. Linam WM, Margolis PA, Staat MA et infections in total joint arthroplasty. CJ, Cohen DB. Incidence of surgi- al. Risk factors associated with surgical J Bone Joint Surg Br. 2008; 90:915-9. cal site infection following adult site infection after pediatric posterior 802. Fish DN, Hoffman HM, Danziger LH. spinal deformity surgery: an analysis spinal fusion procedure. Infect Control Antibiotic impregnated cement use in of patient risk. Eur Spine J. 2010; Hosp Epidemiol. 2009; 30:109-16. U.S. hospitals. Am J Hosp Pharm. 1992; 19:982-8. 786. Fitzgerald RH. Infections of hip pros- 49:2469-74. 771. Wimmer C, Gluch H, Franzreb M et thesis and artificial joints.Infect Dis 803. Malik MH, Gambhir AK, Bale L et al. al. Predisposing factors for infection Clin North Am. 1989; 3:329-38. Primary total hip replacement: a com- in spine surgery: a survey of 850 spi- 787. Southwell-Keely JP, Russo RR, App parison of a nationally agreed guide to nal procedures. J Spinal Disord. 1998; B et al. Antibiotic prophylaxis in hip practice and current surgical technique 11:125-8. fracture surgery: a meta-analysis. Clin as determined by the North West Re- 772. Friedman ND, Sexton DJ, Connelly Orthop Relat Res. 2004; 410:179-84. gional Arthroplasty Registry. Ann R SM et al. Risk factors for surgical site 788. Gillespie WJ, Walenkamp G. Antibiotic Coll Surg Engl. 2004; 86:113-8. infection complicating laminectomy. prophylaxis for surgery for proximal 804. Bourne RB. Prophylactic use of an- Infect Control Hosp Epidemiol. 2007; femoral and other closed long bone tibiotic bone cement: an emerging 28:1060-5. fractures. Cochrane Database Syst Rev. standard—in the affirmative. J Arthro- 773. Olsen MA, Nepple JJ, Riew D et al. Risk 2001; 1:CD000244. plasty. 2004; 19(suppl 1):69-72. factors for surgical site infection fol- 789. Hahnel J, Burdekin H, Anand S. Re- 805. Engesaeter LB, Lie SA, Espehaug B lowing orthopaedic spinal operations. admissions following hip fracture et al. Antibiotic prophylaxis in total J Bone Joint Surg Am. 2008; 90:62-9. surgery. Ann R Coll Surg Engl. 2009; hip arthroplasty: effects of antibiotic 774. Hollenbeak CS, Lave JR, Zeddies T et 91:591-5. prophylaxis systemically and in bone al. Factors associated with risk of surgi- 790. Gulihar A, Nixon M, Jenkins D et al. cement on the revision rate of 22,170 cal wound infections. Am J Med Qual. Clostridium difficile in hip fracture primary hip replacements followed 0 to 2006; 21(suppl):29S-34S. patients: prevention, treatment and 14 years in the Norwegian Arthroplasty 775. Pull Ter Gunne AF, Cohen DB. In- associated mortality. Injury. 2009; Register. Acta Orthop Scand. 2003; cidence, prevalance, and analysis of 40:746-51. 74:644-51. risk factors for surgical site infection 791. Cunha BA, Gossling HR, Pasternak HS 806. Espehaug B, Engesaeter LB, Vollset SE following adult spinal surgery. Spine. et al. The penetration characteristics of et al. Antibiotic prophylaxis in total hip 2009; 34:1422-8. cefazolin, cephalothin, and cephradine arthroplasty: review of 10,905 primary 776. Fang A, Hu SS, Endres N et al. Risk fac- into bone in patients undergoing total cemented total hip replacements re- tors for infection after spinal surgery. hip replacement. J Bone Joint Surg. ported to the Norwegian Arthroplasty Spine. 2005; 30:1460-5. 1977; 59:856-9. Register, 1987 to 1995. J Bone Joint Surg 777. Patel N, Bagan B, Vadera S et al. Obe- 792. Starks I, Ayub G, Walley G et al. Single- Br. 1997; 79:590-5. sity and spine surgery: relations to dose cefuroxime with gentamicin 807. Jiranek WA, Hanssen AD, Greenwald perioperative complications. J Neuro- reduces Clostridium difficile-associated AS. Antibiotic-loaded bone cement surg Spine. 2007; 6:291-7. disease in hip-fracture patients. J Hosp for infection prophylaxis in total joint 778. Petignat C, Francioli P, Harbarth S et Infect. 2008; 70:21-6. replacement. J Bone Joint Surg. 2006; al. Cefuroxime prophylaxis is effective 793. DeFrances CJ, Hall MJ. 2005 National 88:2487-500. in noninstrumented spine surgery: Hospital Discharge Survey. Adv Data. 808. McQueen MM, Hughes SP, May P et al. a double-blind, placebo-controlled 2007; 385:1-19. Cefuroxime in total joint arthroplasty. study. Spine. 2008; 33:1919-24. 794. Glazebrook MA, Arsenault K, Dunbar Intravenous or in bone cement. J Ar- 779. Walters R, Moore R, Fraser R. Pen- M. Evidence-based classification of throplasty. 1990; 5:169-72. etration of cefazolin in human lum- complications in total ankle arthro- 809. Josefsson G, Kolmert L. Prophylaxis bar intervertebral disk. Spine. 2006; plasty. Foot Ankle Int. 2009; 30:945-9. with systematic antibiotics versus gen- 31:567-70. 795. Gougoulias N, Khanna A, Maffulli N. tamicin bone cement in total hip ar- 780. Rimoldi RL, Haye W. The use of anti- How successful are current ankle re- throplasty. A ten-year survey of 1,688 biotics for wound prophylaxis in spinal placements? A systematic review of the hips. Clin Orthop Relat Res. 1993; surgery. Orthop Clin North Am. 1996; literature. Clin Orthop Relat Res. 2010; 292:210-4. 27:47-52. 468:199-208. 810. Hanssen AD, Osmon DR. The use 781. American Academy of Orthopaedic 796. Blom AW, Brown J, Taylor AH et al. of prophylactic antimicrobial agents Surgeons. Information statement: the Infection after total knee arthroplasty. during and after hip arthroplasty. Clin use of prophylactic antibiotics in or- J Bone Joint Surg Br. 2004; 86:688-91. Orthop Relat Res. 1999; 369:124-38. thopaedic medicine and the emergence 797. Kasten MD, Skinner HB. Total elbow 811. Jiranek W. Antibiotic-loaded cement of vancomycin-resistant bacteria. arthroplasty. An 18-year experience. in total hip replacement: current in- www.aaos.org/about/papers/advistmt/ Clin Orthop Relat Res. 1993; 290:177- dications, efficacy, and complications. 1016.asp (accessed 2008 May 13). 88. Orthopedics. 2005; 28(suppl):s873-7. 782. Dobzyniak MA, Fischgrund JS, Hankins 798. Periti P, Stringa G, Mini E et al. 812. Diefenbeck M, Mückley T, Hofman S et al. Single versus multiple dose Comparative multicenter trial of tei- GO. Prophylaxis and treatment of antibiotic prophylaxis in lumbar disc coplanin versus cefazolin for antimi- implant-related infections by local ap- surgery. Spine. 2003; 28:453-5. crobial prophylaxis in prosthetic joint plication of antibiotics. Injury. 2006; 783. Milstone AM, Maragakis LL, Townsend implant surgery. Eur J Clin Microbiol 37(suppl 2):S95-104. T et al. Timing of preoperative anti- Infect Dis. 1999; 18:113-9. 813. Hanssen AD. Prophylactic use of biotic prophylaxis: a modifiable risk 799. Minnema B, Vearncombe M, Augustin antibiotic bone cement: an emerging factor for deep surgical site infections A et al. Risk factors for surgical-site standard—in opposition. J Arthro- after pediatric spinal fusion. Pediatr infection following primary total knee plasty. 2004; 19(suppl 1):73-7. Infect Dis J. 2008; 27:704-8. arthroplasty. Infect Control Hosp Epide- 814. Block JE, Stubbs HA. Reducing the 784. Coe JD, Smithe JS, Berven S et al. miol. 2004; 25:477-80. risk of deep wound infection in pri- Complications of spinal fusion for 800. Blom AW, Taylor AH, Pattison G et al. mary joint arthroplasty with antibi- Scheuermann kyphosis: a report of the Infection after total hip arthroplasty. otic bone cement. Orthopedics. 2005; Scoliosis Research Society Morbidity J Bone Joint Surg Br. 2003; 85:956-9. 28:1334-45.

276 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

815. Wininger DA, Fass RJ. Antibiotic- infections in urologic operations. Int J 842. Gomelsky A, Dmochowski RR. Anti- impregnated cement and beads for Urol. 2004; 11:941-7. biotic prophylaxis in urologic pros- orthopedic infections. Antimicrob Che- 829. Richter S, Lang R, Zur F et al. Infected thetic surgery. Curr Pharm Des. 2003; mother. 1996; 40:2675-9. urine as a risk factor for postprosta 9:989-96. 816. Nelson CL, Green TG, Porter RA et al. tectomy wound infection. Infect Con- 843. Hoffelt SC, Wallner K, Merrick G. Epi- One day versus seven days of preven- trol Hosp Epidemiol. 1991; 12:147-9. didymitis after prostate brachytherapy. tive antibiotic therapy in orthopedic 830. Carson CC. Diagnosis, treatment and Urology. 2004; 63:293-6. surgery. Clin Orthop Relat Res. 1983; prevention of penile prosthesis infec- 844. Ferguson KH, McNeil JJ, Morey AF. 176:258-63. tion. Int J Impot Res. 2003; 15(suppl Mechanical and antibiotic bowel 817. Matsumoto T, Kiyota H, Matsukawa 5):S139-46. preparation for urinary diversion sur- M et al. Japanese guidelines for pre- 831. Schaeffer AJ, Montorsi F, Scattoni V et gery. J Urol. 2002; 167:2352-6. vention of perioperative infections al. Comparison of a 3-day with a 1-day 845. Pearle MS, Roehrborn CG. Antimicro- in urological field.Int J Urol. 2007; regimen of an extended-release formu- bial prophylaxis prior to shock wave 14:890-909. lation of ciprofloxacin as antimicrobial lithotripsy in patients with sterile urine 818. Wolf JS Jr, Bennett CJ, Dmochowski prophylaxis for patients undergoing before treatment: a meta-analysis and RR et al. Best practice policy statement transrectal needle biopsy of the pros- cost-effectiveness analysis. Urology. on urologic surgery antimicrobial tate. BJU Int. 2007; 100:51-7. 1997; 49:679-86. prophylaxis. J Urol. 2008; 179:1379-90. 832. Hara N, Kitamura Y, Saito T et al. 846. Berry A, Barratt A. Prophylactic an- 819. Kapoor DA, Klimberg IW, Malek GH Perioperative antibiotics in radi- tibiotic use in transurethral prostatic et al. Single-dose oral ciprofloxacin cal cystectomy with ileal conduit resection: a meta analysis. J Urol. 2002; versus placebo for prophylaxis during urinary diversion: efficacy and risk 167:571-7. transrectal prostate biopsy. Urology. of antimicrobial prophylaxis on the 847. Qiang W, Jianchen W, MacDonald R et 1998; 52:552-8. operation day alone. Int J Urol. 2008; al. Antibiotic prophylaxis for transure- 820. Latthe PM, Foon R, Toozs-Hobson P. 15:511-5. thral prostatic resection in men with Prophylactic antibiotics in urodynam- 833. Meir DB, Livne PM. Is prophylactic preoperative urine containing less than ics: a systematic review of effectiveness antimicrobial treatment necessary 100,000 bacteria per ml: a systematic and safety. Neurourol Urodyn. 2008; after hypospadias repair? J Urol. 2004; review. J Urol. 2005; 173:1175-81. 27:167-73. 171:2621-2. 848. Knopf HJ, Graff H, Schulze H. Peri- 821. Kartal ED, Yenilmez A, Kiremitci A 834. Doğan HS, Şahin A, Çetinkaya Y et operative antibiotic prophylaxis in et al. Effectiveness of ciprofloxacin al. Antibiotic prophylaxis in percuta- ureteroscopic stone removal. Eur Urol. prophylaxis in preventing bacteriuria neous nephrolithotomy: prospective 2003; 44:115-8. caused by urodynamic study: a blind, study in 81 patients. J Endourol. 2002; 849. Brewster SF, MacGowan AP, Gingell randomized study of 192 patients. 16:649-53. JC. Antimicrobial prophylaxis for tran- Urology. 2006; 67:1149-53. 835. Cox CE. Comparison of intravenous srectal prostatic biopsy: a prospective, 822. Wagenlehner FM, Wagenlehner C, ciprofloxacin and intravenous cefo- randomized trial of cefuroxime versus Schinzel S et al. Prospective, ran taxime for antimicrobial prophylaxis in piperacillin/tazobactam. Br J Urol. domized, multicentric, open, transurethral surgery. Am J Med. 1989; 1995; 76:351-4. comparative study on the efficacy 87(suppl 5A):252S-254S. 850. DeBessonet DA, Merlin AS. Antibiotic of a prophylactic single dose of 500 836. Cam K, Kayikci A, Akman Y et al. prophylaxis in elective genitourinary mg levofloxacin versus 1920 mg Prospective assessment of the efficacy tract surgery: a comparison of single- trimethoprim/sulfamethoxazole versus of single dose versus traditional 3-day dose preoperative cefotaxime and a control group in patients undergoing antimicrobial prophylaxis in 12-core multiple-dose cefoxitin. J Antimicrob TUR of the prostate. Eur Urol. 2005; transrectal prostate biopsy. Int J Urol. Chemother. 1984; 14(suppl B):271-5. 47:549-56. 2008; 18:997-1001. 851. Christiano AP, Hollowell CM, Kim H 823. Takeyama K, Takahashi S, Maeda T et 837. Aron M, Rajeev TP, Gupta NP. Antibi- et al. Double-blind randomized com- al. Comparison of 1-day, 2-day, and otic prophylaxis for transrectal needle parison of single-dose ciprofloxacin 3-day administration of antimicrobial biopsy of the prostate: a randomized versus intravenous cefazolin in patients prophylaxis in radical prostatectomy. controlled study. BJU Int. 2000; 85:682- undergoing outpatient endourologic J Infect Chemother. 2007; 13:320-3. 5. surgery. Urology. 2000; 55:182-5. 824. Briffaux R, Coloby P, Bruyere F et al. 838. Isen K, Küpeli B, Sinik Z et al. Antibi- 852. Bhatia NN, Karram MM, Bergman One preoperative dose randomized otic prophylaxis for transrectal biopsy A. Role of antibiotic prophylaxis in against 3-day antibiotic prophylax- of the prostate: a prospective random- retropubic surgery for stress urinary is for transrectal ultrasonography- ized study of the prophylactic use of incontinence. Obstet Gynecol. 1989; guided prostate biopsy. BJU Int. 2008; single dose oral fluoroquinolone versus 74:637-9. 103:1069-73. trimethoprim-sulfamethoxazole. Int 853. Terai A, Ichioka K, Kohei N et al. An- 825. Bootsma AM, Pes MP, Geerlings SE et Urol Nephrol. 1999; 31:491-5. tibiotic prophylaxis in radical prosta al. Antibiotic prophylaxis in urologic 839. Johnson MI, Merrilees D, Robson tectomy: 1-day versus 4-day treat- procedures: a systematic review. Eur WA et al. Oral ciprofloxacin or tri- ments. Int J Urol. 2006; 13:1488-93. Urol. 2008; 54:1270-86. methoprim reduces bacteriuria after 854. Gombert ME, DuBouchet L, Aulicino 826. Grabe M, Bishop MC, Bjerklund- flexible cystoscopy. BJU Int. 2007; TM et al. Brief report: intravenous Johansen TE et al. Guidelines on 100:826-9. ciprofloxacin versus cefotaxime pro- urological infections. www.uroweb.org 840. Yokoyama M, Fujii Y, Yoshida S et al. phylaxis during transurethral surgery. (accessed 2010 Mar 18). Discarding antimicrobial prophylaxis Am J Med. 1989; 87(suppl 5A): 250S- 827. Yamamoto S, Kanamaru S, Kunishima for transurethral resection of bladder 251S. Y et al. Perioperative antimicrobial tumor: a feasibility study. Int J Urol. 855. Klimberg IW, Malek GH, Cox CE. prophylaxis in urology: a multi-center 2009; 16:61-3. Single-dose oral ciprofloxacin com- prospective study. J Chemother. 2005; 841. Takeyama K, Matsukawa M, Kunishima pared with cefotaxime and placebo 17:189-97. Y et al. Incidence of and risk factors for prophylaxis during transurethral 828. Hamasuna R, Betsunoh H, Sueyoshi T for surgical site infections in patients surgery. J Antimicrob Chemother. 1999; et al. Bacteria of preoperative urinary with radical cystectomy with urinary 43(suppl A):77-84. tract infections contaminate the sur- diversion. J Infect Chemother. 2005; 856. Gibbons RP, Stark RA, Gorrea RJ et al. gical fields and develop surgical site 11:177-81. The prophylactic use—or misuse—of

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 277 ASHP Report Antimicrobial prophylaxis

antibiotics in transurethral prostatec- eral arterial operations: a randomized, 888. Hasselgren PO, Ivarson L, Risberg B tomy. J Urol. 1978; 119:381-3. prospective trial. South Med J. 1997; et al. Effects of prophylactic antibiot- 857. Ramsey E, Sheth NK. Antibiotic pro- 90:16-22. ics in vascular surgery. A prospective, phylaxis in patients undergoing prosta- 873. Ryan JM, Ryan BM, Smith TP. Anti- randomized, double-blind study. Ann tectomy. Urology. 1983; 21:376-8. biotic prophylaxis in interventional Surg. 1984; 200:86-92. 858. Cormio L, Berardi B, Callea A et al. radiology. J Vasc Interv Radiol. 2004; 889. Risberg B, Drott C, Dalman P et al. Antimicrobial prophylaxis for tran- 15:547-56. Oral ciprofloxacin versus intravenous srectal prostatic biopsy: a prospective 874. McDermott VG, Schuster MG, Smith cefuroxime as prophylaxis against study of ciprofloxacin vs. piperacillin/ TP. Antibiotic prophylaxis in vascular postoperative infection in vascular tazobactam. BJU Int. 2002; 90:700-2. and interventional radiology. Am J surgery: a randomized double-blind, 859. Sakura M, Kawakami S, Yoshida S et al. Roentgenol. 1997; 169:31-8. prospective multicentre study. Eur J Prospective comparative study of sin- 875. Beddy P, Ryan JM. Antibiotic prophy- Endovasc Surg. 1995; 10:346-51. gle dose versus 3-day administration of laxis in interventional radiology— 890. Stewart AH, Eyers PS, Earnshaw JJ. antimicrobial prophylaxis in minimum anything new? Tech Vasc Interv Radiol. Prevention of infection in peripheral incision endoscopic radical prostatec- 2006; 9:69-76. arterial reconstruction: a systematic tomy. Int J Urol. 2008; 15:328-31. 876. Malek AM, Higashida RT, Reilly LM et review and meta-analysis. J Vasc Surg. 860. Hills NH, Bultitude MI, Eykyn S. al. Subclavian arteritis and pseudoan- 2007; 46:148-55. Co-trimoxazole in prevention of bac- eurysm formation secondary to stent 891. Murray BE. Problems and dilemmas teriuria after prostatectomy. Br Med J. infection. Cardiovasc Interv Radiol. of antimicrobial resistance. Pharmaco- 1976; 2:498-9. 2000; 23:57-60. therapy. 1992; 12:86-93. 861. Matthew AD, Gonzales R, Jeffords D 877. Venkatesan AM, Kundu S, Sacks D et al. 892. Earnshaw JJ, Slack RC, Hopkinson BR et al. Prevention of bacteriuria after Practice guideline for adult antibiotic et al. Risk factors in vascular surgical transurethral prostatectomy with prophylaxis during vascular and inter- sepsis. Ann R Coll Surg Engl. 1988; nitrofurantoin macrocrystals. J Urol. ventional radiology procedures. J Vasc 70:139-43. 1978; 120:442-3. Interv Radiol. 2010; 21:1611-30. 893. Hall JC, Christiansen KJ, Goodman M 862. Hammarsten J, Lindqvist K. Nor- 878. Thompson M. An audit demonstrat- et al. Duration of antimicrobial pro- floxacin as prophylaxis against urethral ing a reduction in MRSA infection in phylaxis in vascular surgery. Am J Surg. strictures following transurethral a specialized vascular unit resulting 1998; 175:87-90. resection of the prostate: an open, from a change in infection control pro- 894. Fishman JA. Infection in solid-organ prospective, randomized study. J Urol. tocol. Eur J Vasc Endovasc Surg. 2006; transplant recipients. N Engl J Med. 1993; 150:1722-4. 31:609-15. 2007; 357:2601-14. 863. Siracusano S, Knez R, Tiberio A et 879. Morange-Saussier V, Giraudeau B, 895. Fischer SA. Infections in the trans- al. The usefulness of antibiotic pro- van der Mee N et al. Nasal carriage of plant recipient. Med Health R I. 2002; phylaxis in invasive urodynamics in methicillin-resistant Staphylococcus 85:125-7. postmenopausal female subjects. Int aureus in vascular surgery. Ann Vasc 896. Soave R. Prophylaxis strategies for Urogynecol J. 2008; 19:939-42. Surg. 2006; 20:767-72. solid-organ transplantation. Clin Infect 864. Patel U, Kirby R. Infections after 880. Taylor MD, Napolitano LM. Methicillin- Dis. 2001; 33(suppl 1):s26-31. prostate biopsy and antibiotic resis- resistant Staphylococcus aureus infec- 897. Keough WL, Michaels MG. Infectious tance. BJU Int. 2008; 101:1201-4. tions in vascular surgery: increasing complications in pediatric solid organ 865. Hall JC, Christiansen KJ, England P et prevalence. Surg Infect. 2004; 5:180-7. transplantation. Pediatr Clin North al. Antibiotic prophylaxis for patients 881. Grimble SA, Magee TR, Galland RB. Am. 2003; 50:1451-69. undergoing transurethral resection of Methicillin resistant Staphylococcus 898. United Network for Organ Sharing. the prostate. Urology. 1996; 47:852-6. aureus in patients undergoing major Organ Procurement and Transplanta- 866. Liu GG, Nguyen T, Nichol MB. An eco- amputation. Eur J Vasc Endovasc Surg. tion Network data (as of September 5, nomic analysis of antimicrobial pro- 2001; 22:215-8. 2008). http://optn.transplant.hrsa.gov/ phylaxis against urinary tract infection 882. Nasim A, Thompson MM, Naylor AR data/ (accessed 2012 Dec 9). in patients undergoing transurethral et al. The impact of MRSA on vascu- 899. Cai J. Thoracic transplantation in the resection of the prostate. Clin Ther. lar surgery. Eur J Vasc Endovasc Surg. United States: an analysis of UNOS 1999; 21:1589-603. 2001; 22:211-4. registry data. Clin Transplant. 2006; 867. Burnakis TG. Surgical antimicrobial 883. Cowie SE, Ma I, Lee SK et al. Noso- 41-56. prophylaxis: principles and guidelines. comial MRSA infection in vascular 900. Fong I, Baker C, McKee D. The value Pharmacotherapy. 1984; 4:248-71. surgery patients: impact on patient of prophylactic antibiotics in aorta- 868. Homer-Vanniasinkam S. Surgical site outcome. Vasc Endovasc Surg. 2005; coronary bypass operations. J Thorac and vascular infections: treatment 39:327-34. Cardiovasc Surg. 1979; 78:908-13. and prophylaxis. Int J Infect Dis. 2007; 884. Fawley WN, Parnell P, Hall J et al. 901. Penketh A, Wansbrough-Jones M, 11:S17-22. Surveillance for mupirocin resistance Wright E et al. Antibiotic prophylaxis 869. Zibari GB, Gadallah MF, Landreneau following introduction of routine for coronary artery bypass graft sur- M et al. Preoperative vancomycin peri-operative prophylaxis with na- gery. Lancet. 1985; 1:1500. prophylaxis decreases incidence of sal mupirocin. J Hosp Infect. 2006; 902. Muñoz P, Menasalvas A, Bernaldo de postoperative hemodialysis vascular 62:327-32. Quirós JC et al. Postsurgical mediasti- access infections. Am J Kidney Dis. 885. Kaiser A, Clayton KR, Mulherin JL et nitis: a case-control study. Clin Infect 1997; 30:343-8. al. Antibiotic prophylaxis in vascular Dis. 1997; 25:1060-4. 870. Naylor AR, Payne D, London NJ et al. surgery. Ann Surg. 1978; 188:283-9. 903. Filsoufi F, Rahmanian PB, Castillo JG Prosthetic patch infection after carotid 886. Edwards WH, Kaiser AB, Kernodle DS et al. Incidence, treatment strategies endarterectomy. Eur J Vasc Endovasc et al. Cefuroxime versus cefazolin as and outcome of deep sternal wound Surg. 2002; 23:11-6. prophylaxis in vascular surgery. J Vasc infection after orthotopic heart trans- 871. Richet HM, Chidiac C, Prat A et al. Surg. 1992; 15:35-42. plantation. J Heart Lung Transplant. Analysis of risk factors for surgical 887. Edwards WH Jr, Kaiser AB, Tapper S 2007; 26:1084-90. wound infections following vascular et al. Cefamandole versus cefazolin 904. Abid Q, Nkere UU, Hasan A et al. Me- surgery. Am J Med. 1991; 91:171S-172S. in vascular surgical wound infection diastinitis in heart and lung transplan- 872. Ross CB, Wheeler WG II, Jones MJ et al. prophylaxis: cost-effectiveness and risk tation: 15 years experience. Ann Thorac Ceftriaxone versus cefazolin in periph- factors. J Vasc Surg. 1993; 18:470-5. Surg. 2003; 75:1565-71.

278 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis

905. Carrier M, Perrault LP, Pellerin M et 920. Campos S, Caramori M, Teixeira R et 937. Kim YJ, Kim SI, Wie SH et al. Infec- al. Sternal wound infection after heart al. Bacterial and fungal pneumonia tious complications in living-donor transplantation: incidence and results after lung transplantation. Transplant liver transplant recipients: a 9-year with aggressive surgical treatment. Ann Proc. 2008; 40:822-4. single-center experience. Transplant Thorac Surg. 2001; 72:719-24. 921. Krishnam MS, Suh RD, Tomasian A et Infect Dis. 2008; 10:316-24. 906. Ramos A, Asensio A, Muñoz E et al. al. Postoperative complications of lung 938. Hollenbeak CS, Alfrey EJ, Souba WW. Incisional surgical infection in heart transplantation: radiologic findings The effect of surgical site infections on transplantation. Transpl Infect Dis. along a time continuum. Radiograph- outcomes and resource utilization after 2008; 10:298-302. ics. 2007; 27:957-74. liver transplantation. Surgery. 2001; 907. Sénéchal M, LePrince P, Tezenas du 922. Helmi M, Love RB, Welter D et al. 130:388-95. Montcel S et al. Bacterial mediastinitis Aspergillus infection in lung transplant 939. Kibbler CC. Infections in liver trans- after heart transplantation: clinical recipients with cystic fibrosis: risk plantation: risk factors and strategies presentation, risk factors and treat- factors and outcomes comparison to for prevention. J Hosp Infect. 1995; ment. J Heart Lung Transplant. 2004; other types of transplant recipients. 30(suppl):209-17. 23:165-70. Chest. 2003; 123:800-8. 940. Wade JJ, Rolando N, Hayllar K et al. 908. Mattner F, Fischer S, Weissbrodt H et 923. Russo MJ, Iribarne A, Hong KN et al. Bacterial and fungal infections after al. Post-operative nosocomial infec- High lung allocation score is associated liver transplantation: an analysis tions after lung and heart transplanta- with increased morbidity and mor of 284 patients. Hepatology. 1995; tion. J Heart Lung Transplant. 2007; tality following transplantation. Chest. 21:1328-36. 26:241-9. 2010; 137:651-7. 941. Shepherd RW, Turmelle Y, Nadler M et 909. Van De Beek D, Kremer WK, Del Pozo 924. Dowling RD, Zenati M, Yousem S et al. Risk factors for rejection and infec- JL et al. Effect of infectious diseases on al. Donor-transmitted pneumonia in tion in pediatric liver transplantation. outcome after heart transplant. Mayo experimental lung allografts. J Thorac Am J Transplant. 2008; 8:396-403. Clin Proc. 2008; 83:304-8. Cardiovasc Surg. 1992; 103:767-72. 942. Hollenbeak CS, Alfrey EJ, Sheridan K et 910. Keay S. Cardiac transplantation: 925. Low DE, Kaiser LR, Haydock DA et al. al. Surgical site infections following pe- pre-transplant infectious diseases The donor lung: infectious and patho- diatric liver transplantation: risks and evaluation and post-transplant pro- logic factors affecting outcome in lung costs. Transpl Infect Dis. 2003; 5:72-8. phylaxis. Curr Infect Dis Rep. 2002; transplantation. J Thorac Cardiovasc 943. Arnow PM, Carandang GC, Zabner R 4:285-92. Surg. 1993; 106:614-21. et al. Randomized controlled trial of 911. Kaiser AB. Use of antibiotics in cardiac 926. Steinbach S, Sun L, Jiang RZ et al. selective bowel decontamination for and thoracic surgery. In: Sabiston DC Transmissibility of Pseudomonas cepa- prevention of infections following liver Jr, Spencer FC, eds. Surgery of the cia infection in clinic patients and transplantation. Clin Infect Dis. 1996; chest. 6th ed. Philadelphia: W. B. Saun- lung-transplant recipients with cystic 22:997-1003. ders; 1995:98-116. fibrosis.N Engl J Med. 1994; 331:981-7. 944. Colonna JO II, Drew WJ, Brill JE et al. 912. Khaghani A, Martin M, Fitzgerald M 927. Dauber JH, Paradis IL, Dummer JS. Infectious complications in liver trans- et al. Cefotaxime and flucloxacillin Infectious complications in pulmonary plantation. Arch Surg. 1988; 123:360-4. as antibiotic prophylaxis in cardiac allograft recipients. Clin Chest Med. 945. George DL, Arnow PM, Fox AS et al. transplantation. Drugs. 1988; 35(suppl 1990; 11:291-308. Bacterial infection as a complication 2):124-6. 928. Deusch E, End A, Grimm M et al. Early of liver transplantation: epidemiology 913. Montoya JG, Giraldo LF, Efron B et al. bacterial infections in lung transplant and risk factors. Rev Infect Dis. 1991; Infectious complications among 620 recipients. Chest. 1993; 104:1412-6. 13:387-96. consecutive heart transplant patients 929. Paradis IL, Williams P. Infection after 946. Uemoto S, Tanaka K, Fujita S et al. In- at Stanford University Medical Center. lung transplantation. Semin Respir In- fectious complications in living related Clin Infect Dis. 2001; 33:629-40. fect. 1993; 8:207-15. liver transplantation. J Pediatr Surg. 914. Petri WA Jr. Infections in heart trans- 930. Husain S, Zaldonis D, Kusne S et 1994; 29:514-7. plant recipients. Clin Infect Dis. 1994; al. Variation in antifungal prophy- 947. Kusne S, Dummer JS, Singh N et al. 18:141-8. laxis strategies in lung transplantation. Infections after liver transplantation. 915. Trulock EP. Lung transplantation. Am Transpl Infect Dis. 2006; 8:213-8. An analysis of 101 consecutive cases. J Respir Crit Care Med. 1997; 155:789- 931. Noyes BE, Kurland G, Orenstein DM. Medicine. 1988; 67:132-43. 818. Lung and heart-lung transplantation 948. Singh N, Paterson DL, Gayowski T 916. U.S. Department of Health and in children. Pediatr Pulmonol. 1997; et al. Predicting bacteremia and bac- Human Services. Organ Procure- 23:39-48. teremic mortality in liver transplant ment and Transplantation Network/ 932. Moreno R, Berenguer M. Post-liver recipients. Liver Transpl. 2000; 6:54-61. Scientific Registry of Transplant Re- transplantation medical complications. 949. Hjortrup A, Rasmussen A, Hansen cipients annual report. Table 12.4. Ann Hepatol. 2006; 5:77-85. BA et al. Early bacterial and fungal Transplant recipient characteristics, 933. Muiesan P, Vergani D, Mieli-Vergani infections in liver transplantation after 1999 to 2008. Recipients of deceased G. Liver transplantation in children. oral selective bowel decontamination. donor lungs. 2009 May 4. http://optn. J Hepatol. 2007; 46:340-8. Transplant Proc. 1997; 29:3106-10. transplant.hrsa.gov/ar2009/1204_rec- 934. United Network for Organ Sharing. 950. Villacian JS, Paya CV. Prevention of dgn_lu.htm (accessed 2011 Mar 17). Organ Procurement and Transplan- infections in solid organ transplant 917. Hosenpud JD, Novick RJ, Bennett LE et tation Network: data. http://optn. recipients. Transpl Infect Dis. 1999; al. The registry of the International So- transplant.hrsa.gov/data/. Based on 1:50-64. ciety for Heart and Lung Transplanta- OPTN data as of September 26, 2008. 951. Asensio A, Ramos A, Cuervas-Mons V tion: thirteenth official report.J Heart 935. García Prado ME, Matia EC, Ciuro et al. Effect of antibiotic prophylaxis on Lung Transplant. 1996; 15:655-74. FP et al. Surgical site infection in liver the risk of surgical site infection in or- 918. Davis RD Jr, Pasque MK. Pulmo- transplant recipients: impact of the thotopic liver transplant. Liver Transpl. nary transplantation. Ann Surg. 1995; type of perioperative prophylaxis. 2008; 14:799-805. 221:14-28. Transplantation. 2008; 85:1849-54. 952. Arnow PM, Zachary KC, Thistlethwaite 919. Kotloff RM, Zuckerman JB. Lung 936. Kuo PC, Bartlett ST, Lim JW et al. Se- JR et al. Pathogenesis of early operative transplantation for cystic fibrosis. lective bowel decontamination in hos- site infections after orthotopic liver Special considerations. Chest. 1996; pitalized patients awaiting liver trans- transplantation. Transplantation. 1998; 109:787-98. plantation. Am J Surg. 1997; 174:745-9. 65:1500-3.

Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 279 ASHP Report Antimicrobial prophylaxis

953. Mattner F, Kola A, Fischer S et al. antibiotics in liver transplant patients. tamination: a controlled trial in liver Impact of bacterial and fungal donor Antimicrob Agents Chemother. 1992; transplant recipients. Transplantation. organ contamination in lung, heart- 36:2125-30. 2002; 74:123-8. lung, heart and liver transplantation. 968. Gorensek MJ, Carey WD, Washington 981. González-Segura C, Pascual M, Garcia Infection. 2008; 36:207-12. JA II et al. Selective bowel decontami- Huete L et al. Donors with positive 954. Barkholt LM, Andersson J, Ericzon BG nation with quinolones and nystatin blood culture: could they transmit et al. Stool cultures obtained before liv- reduces gram-negative and fungal in- infections to the recipients? Transplant er transplantation are useful for choice fections in orthotopic liver transplant Proc. 2005; 37:3664-6. of perioperative antibiotic prophylaxis. recipients. Cleve Clin J Med. 1993; 982. Lumbreras C, Cuervas-Mons V, Jara Transplant Int. 1997; 10:432-8. 60:139-44. P et al. Randomized trial of flucon- 955. Hellinger WC, Yao JD, Alvarez S et al. 969. Piselli P, Zanfi C, Corazza V et al. In- azole versus nystatin for the prophy- A randomized, prospective, double- cidence and timing of infections after laxis of Candida infection following blinded evaluation of selective bowel liver transplant in Italy. Transplant liver transplantation. J Infect Dis. 1996; decontamination in liver transplanta- Proc. 2007; 39:1950-2. 174:583-8. tion. Transplantation. 2002; 73:1904-9. 970. Desai D, Desai N, Nightingale P et 983. Winston DJ, Pakrasi A, Busuttil RW. 956. Zwaveling JH, Maring JK, Klompmaker al. Carriage of methicillin-resistant Prophylactic fluconazole in liver IJ et al. Selective decontamination of the Staphylococcus aureus is associated transplant recipients. A randomized, digestive tract to prevent postoperative with an increased risk of infection after double-blind, placebo-controlled trial. infection: a randomized placebo- liver transplantation. Liver Transpl. Ann Intern Med. 1999; 131:729-37. controlled trial in liver transplant pa- 2003; 9:754-9. 984. Sharpe MD, Ghent C, Grant D et al. tients. Crit Care Med. 2002; 30:1204-9. 971. Rayes N, Seehofer D, Theruvath T Efficacy and safety of itraconazole 957. Hashimoto M, Sugawara Y, Tamura et al. Supply of pre- and probiotics prophylaxis for fungal infections after S et al. Impact of new methicillin- reduces bacterial infection rates after orthotopic liver transplantation: a resistant Staphylococcus aureus carriage liver transplantation—a randomized, prospective, randomized, double-blind postoperatively after living donor liver double-blind trial. Am J Transplant. study. Transplantation. 2003; 76:977- transplantation. Transplant Proc. 2007; 2005; 5:125-30. 83. 39:3271-5. 972. Reid GE, Grim SA, Aldeza CA et al. 985. Castroagudin JF, Ponton C, Bustamante 958. Hashimoto M, Sugawara Y, Tamura S Rapid development of Acinetobacter M et al. Prospective interventional study et al. Bloodstream infection after living baumannii resistance to tigecycline. to evaluate the efficacy and safety of donor liver transplantation. Scand J Pharmacotherapy. 2007; 27:1198-201. liposomal amphotericin B as prophy- Infect Dis. 2008; 40:509-16. 973. Chen H, Zhang Y, Chen YG et al. Sepsis laxis of fungal infections in high-risk 959. Hashimoto M, Sugawara Y, Tamura S resulting from Enterobacter aerogenes liver transplant recipients. Transplant et al. Pseudomonas aeruginosa infection resistant to carbapenems after liver Proc. 2005; 37:3965-7. after living-donor liver transplanta- transplantation. Hepatobiliary Pan- 986. Lorf T, Braun F, Ruchel R et al. Systemic tion in adults. Transpl Infect Dis. 2009; creat Dis Int. 2009; 8:320-2. mycoses during prophylactical use 11:11-9. 974. Chen YG, Zhang Y, Yu YS et al. In of liposomal amphotericin B (Ambi- 960. Bert F, Galdbart JO, Zarrouk V et al. vivo development of carbapenem some) after liver transplantation. My- Association between nasal carriage of resistance in clinical isolates of Entero- coses. 1999; 42:47-53. Staphylococcus aureus and infection in bacter aerogenes producing multiple 987. Tollemar J, Hockerstedt K, Ericzon BG liver transplant recipients. Clin Infect ß-lactamases. Int J Antimicrob Agents. et al. Liposomal amphotericin B pre- Dis. 2000; 31:1295-9. 2008; 32:302-7. vents invasive fungal infections in liver 961. Bert F, Bellier C, Lassel L et al. Risk 975. Bennett JW, Herrera ML, Lewis JS II transplant recipients. A randomized, factors for Staphylococcus aureus infec- et al. KPC-2-producing Enterobacter placebo-controlled study. Transplanta- tion in liver transplant recipients. Liver cloacae and Pseudomonas putida coin- tion. 1995; 59:45-50. Transpl. 2005; 11:1093-9. fection in a liver transplant recipient. 988. Fortun J, Martin-Davila P, Montejo M 962. Chang FY, Singh N, Gayowski T et al. Antimicrob Agents Chemother. 2009; et al. Prophylaxis with caspofungin for Staphylococcus aureus nasal coloniza- 53:292-4. invasive fungal infections in high-risk tion and association with infections in 976. Carignan A, Allard C, Pépin J et al. Risk liver transplant recipients. Transplanta- liver transplant recipients. Transplanta- of Clostridium difficile infection after tion. 2009; 87:424-35. tion. 1998; 65:1169-72. perioperative antibacterial prophylaxis 989. Cruciani M, Mengoli C, Malena M 963. Mehrabi A, Fonouni H, Wente M et before and during an outbreak of in- et al. Antifungal prophylaxis in liver al. Wound complications following fection due to a hypervirulent strain. transplant patients: a systematic review kidney and liver transplantation. Clin Clin Infect Dis. 2008; 46:1838-46. and meta-analysis. Liver Transpl. 2006; Transplant. 2006; 20(suppl 17):97-110. 977. Stelzmueller I, Goegele H, Biebl M et 12:850-8. 964. Kawecki D, Chmura A, Pacholczyk M al. Clostridium difficile in solid organ 990. Weisner RH, Hermans PE, Rakela J et et al. Surgical site infections in liver transplantation—a single-center ex- al. Selective bowel decontamination to recipients in the early posttransplan- perience. Dig Dis Sci. 2007; 52:3231-6. decrease gram-negative aerobic bacte- tation period: etiological agents and 978. Hashimoto M, Sugawara Y, Tamura S rial and candidal colonization and susceptibility profiles.Transplant Proc. et al. Clostridium difficile-associated prevent infection after orthotopic liver 2007; 39:2800-6. diarrhea after living donor liver trans- transplantation. Transplantation. 1988; 965. Bedini A, Codeluppi M, Cocchi S et al. plantation. World J Gastroenterol. 2007; 45:570-4. Gram-positive bloodstream infections 13:2072-6. 991. Safdar N, Said A, Lucey MR. The role in liver transplant recipients: incidence, 979. Bion JF, Badger I, Crosby HA et al. of selective digestive decontamina- risk factors, and impact on survival. Selective decontamination of the diges- tion for reducing infection in patients Transplant Proc. 2007; 39:1947-9. tive tract reduces gram-negative pul- undergoing liver transplantation: a 966. Dar FS, Faraj W, Zaman MB et al. Out- monary colonization but not systemic systematic review and meta-analysis. come of liver transplantation in heredi- endotoxemia in patients undergoing Liver Transpl. 2004; 10:817-27. tary hemochromatosis. Transplant Int. elective liver transplantation. Crit Care 992. Wiesmayr S, Stelzmueller I, Mark 2009; 22:717-24. Med. 1994; 22:40-9. W et al. Experience with the use of 967. Arnow PM, Furmaga K, Flaherty JP 980. Rayes N, Seehofer D, Hansen S et al. piperacillin-tazobactam in pediatric et al. Microbiological efficacy and Early enteral supply of lactobacillus non-renal solid organ transplantation. pharmacokinetics of prophylactic and fiber versus selective bowel decon- Pediatr Transplant. 2007; 11:38-48.

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993. Barker RJ, Mayes JT, Schulak JA. tions and microbiological aspects. urinary tract and surgical site infec- Wound abscesses following retroperi- Transplant Proc. 2004; 36:980-1. tions. J Hosp Infect. 2006; 63:117-23. toneal pancreas transplantation. Clin 1008. Bassetti M, Salvalaggio PR, Topal J et 1025. Celik A, Sifil A, Cavdar C et al. Out- Transplant. 1991; 5:403-7. al. Incidence, timing and site of infec- come of renal transplantation: 7-year 994. Douzdjian V, Abecassis MM, Cooper tions among pancreas transplant re- experience. Transplant Proc. 2001; JL et al. Incidence, management, and cipients. J Hosp Infect. 2004; 56:184-90. 33:2657-9. significance of surgical complications 1009. Barone GW, Hudec WA, Sailors DM et 1026. Lai MK, Huang CC, Chu SH et al. after pancreas-kidney transplantation. al. Prophylactic wound antibiotics for Surgical complications in renal trans- Surg Gynecol Obstet. 1993; 177:451-6. combined kidney and pancreas transplantation. Transplant Proc. 1994; 995. Everett JE, Wahoff DC, Statz C et al. plants. Clin Transplant. 1996; 10:386-8. 26:2165-6. Characterization and impact of wound 1010. Freise CE, Stock PG, Roberts JP et al. 1027. Schmaldienst S, Hoerl WH. Bacterial infection after pancreas transplanta- Low postoperative wound infection infections after renal transplantation. tion. Arch Surg. 1994; 129:1310-7. rates are possible following simultane- Nephron. 1997; 75:140-53. 996. Ozaki CF, Stratta RJ, Taylor RJ et al. ous pancreas-kidney transplantation. 1028. Maraha B, Bonten H, van Hooff H et Surgical complications in solitary pan- Transplant Proc. 1995; 27:3069-70. al. Infectious complications and anti- creas and combined pancreas-kidney 1011. Smets YF, van der Pijl JW, van Dissel JT biotic use in renal transplant recipients transplantations. Am J Surg. 1992; et al. Major bacterial and fungal infec- during a 1-year follow-up. Clin Micro- 164:546-51. tions after 50 simultaneous pancreas- biol Infect. 2001; 7:619-25. 997. Sollinger HW, Ploeg RJ, Eckhoff DE kidney transplantations. Transplant 1029. Ramos A, Asensio A, Muñoz E et al. et al. Two hundred consecutive simul- Proc. 1995; 27:3089-90. Incisional surgical site infection in taneous pancreas-kidney transplants 1012. Douzdjian V, Gugliuzza KK. Wound kidney transplantation. Urology. 2008; with bladder drainage. Surgery. 1993; complications after simultaneous 72:119-23. 114:736-44. pancreas-kidney transplants: midline 1030. Menezes FG, Wey SB, Peres CA et 998. United Network for Organ Shar- versus transverse incision. Transplant al. Risk factors for surgical site infec- ing. Organ Procurement and Trans- Proc. 1995; 27:3130-2. tion in kidney transplant recipients. plantation Network: data. http:// 1013. Bartlett ST. Pancreatic transplanta- Infect Control Hosp Epidemiol. 2008; optn.transplant.hrsa.gov/data/. Based tion after thirty years: still room for 29:771-3. on OPTN data as of October 2, 2008. improvement. J Am Coll Surg. 1996; 1031. Stephan RN, Munschauer CE, Kumar 999. Reddy KS, Stratta RJ, Shokouh-Amiri 183:408-10. MS. Surgical wound infection in renal MH et al. Surgical complications after 1014. Cohen J, Rees AJ, Williams G. A pro- transplantation. Outcome data in 102 pancreas transplantation with portal- spective randomized controlled trial consecutive patients without periop- enteric drainage. J Am Coll Surg. 1999; of perioperative antibiotic prophylaxis erative systemic antibiotic coverage. 189:305-13. in renal transplantation. J Hosp Infect. Arch Surg. 1997; 132:1315-9. 1000. Berger N, Wirmsberger R, Kafka R et 1988; 11:357-63. 1032. Sawyer RG, Pelletier SJ, Pruett TL. In- al. Infectious complications follow- 1015. Hoy WE, May AG, Freeman RB. Prima- creased early morbidity and mortality ing 72 consecutive enteric-drained ry renal transplant wound infections. with acceptable long-term function in pancreas transplants. Transpl Int. 2006; N Y State J Med. 1981; 81:1469-73. severely obese patients undergoing 19:549-57. 1016. Kohlberg WI, Tellis VA, Bhat DJ et al. liver transplantation. Clin Transplant. 1001. Bonatti H, Berger N, Kafka R et al. Wound infections after transplant ne- 1999; 13:126-30. Experience with ATG short course high phrectomy. Arch Surg. 1980; 115:645-6. 1033. Koyle MA, Glasscock RJ, Ward HJ dose induction therapy in a series of 1017. Muakkassa WF, Goldman MH, et al. Declining incidence of wound 112 enteric drained pancreatic trans- Mendez-Picon G et al. Wound infec- infection in cadaveric renal transplant plants. Ann Transplant. 2002; 7:22-7. tions in renal transplant patients. recipient. Urology. 1988; 31:103-6. 1002. Berger N, Guggenbichler S, Steurer W J Urol. 1983; 130:17-9. 1034. Judson RT. Wound infection following et al. Bloodstream infection follow- 1018. Novick AC. The value of intraoperative renal transplantation. Aust N Z J Surg. ing 217 consecutive systemic-enteric antibiotics in preventing renal trans- 1984; 54:223-4. drained pancreas transplants. BMC plant wound infections. J Urol. 1981; 1035. Del Rio G, Dalet F, Chechile G. Antimi- Infect Dis. 2006; 6:127. 125:151-2. crobial prophylaxis in urologic surgery: 1003. Humar A, Kandawamy R, Drangstveit 1019. Ramos E, Karmi S, Alongi SV et al. does it give some benefit?Eur Urol. MB et al. Prolonged preservation Infectious complications in renal 1993; 24:305-12. increases surgical complications after transplant recipients. South Med J. 1036. Midtvedt K, Hartmann A, Midtvedt pancreas transplants. Surgery. 2000; 1980; 73:752-4. T et al. Routine perioperative antibi- 127:545-51. 1020. Rubin RH, Wolfson JS, Cosimi AB et al. otic prophylaxis in renal transplanta- 1004. Pfundstein J, Roghmann MC, Schwalbe Infection in the renal transplant recipi- tion. Nephrol Dial Transplant. 1998; RS et al. A randomized trial of surgical ent. Am J Med. 1981; 70:405-11. 13:1637-41. antimicrobial prophylaxis with and 1021. Tilney NL, Strom TB, Vineyard GC et 1037. Capocasale E, Mazzoni MP, Tondo S without vancomycin in organ trans- al. Factors contributing to the declin- et al. Antimicrobial prophylaxis with plant patients. Clin Transplant. 1999; ing mortality rate in renal transplanta- ceftriaxone in renal transplantation. 13:245-52. tion. N Engl J Med. 1978; 299:1321-5. Prospective study of 170 patients. Che- 1005. Smets YF, van der Pijl JW, van Dissel 1022. Muñoz P. Management of urinary tract motherapy. 1994; 40:435-40. JT et al. Infectious disease complica- infections and lymphocele in renal 1038. Wakelin SJ, Casey J, Robertson A et al. tions of simultaneous pancreas-kidney transplant recipients. Clin Infect Dis. The incidence and importance of bac- transplantation. Nephrol Dial Trans- 2001; 33(suppl 1):S53-7. terial contaminants of cadaveric renal plant. 1997; 12:764-71. 1023. Alangaden GJ, Thyagarajan R, Gruber perfusion fluid.Transplant Int. 2005; 1006. Michalak G, Kwiatkowski A, Bieniasz SA et al. Infectious complications after 17:680-6. M et al. Infectious complications kidney transplantation: current epi- 1039. Zomorrodi A, Buhluli A. Is antibiotic after simultaneous pancreas-kidney demiology and associated risk factors. usage necessary after donor nephrec- transplantation. Transplant Proc. 2005; Clin Transplant. 2006; 20:401-9. tomy? A single center experience. Saudi 37:3560-3. 1024. Dantas SP, Kuboyama RH, Mazzali M J Kidney Dis Transpl. 2008; 19:200-5. 1007. Linhares MM, Gonzalez AM, Triviño et al. Nosocomial infections in renal 1040. Pape L, Offner G, Ehrich JH et al. A T et al. Simultaneous pancreas-kidney transplant patients: risk factors and single center clinical experience in transplantation: infectious complica- treatment implications associated with intensive care management of 104 pe-

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diatric renal transplantations between prescribing habits in plastic surgery. 1071. Kompatscher P, von Planta A, Spicher 1998 and 2002. Pediatr Transplant. J Plast Reconstr Aesthet Surg. 2008; I et al. Comparison of the incidence 2004; 8:39-43. 61:1347-56. and predicted risk of early surgical site 1041. Thorne CH. Techniques and principles 1056. Ahmadi AH, Cohen BE, Shayani P. A infections after breast reduction. Aes- in plastic surgery. In: Thorne CH, prospective study of antibiotic efficacy thetic Plast Surg. 2003; 27:308-14. Beasley RW, Aston SJ et al., eds. Grabb in preventing infection in reduction 1072. Bunn F, Cunningham ME, Handscomb and Smith’s plastic surgery. 6th ed. mammaplasty. Plast Reconstr Surg. K. Prophylactic antibiotics to prevent Philadelphia: Lippincott Williams and 2005; 116:126-31. surgical site infection after breast can- Wilkins; 2007. 1057. Carroll WR, Rosenstiel D, Fix JR et cer surgery. Cochrane Database Syst 1042. Chełmoński A, Jabłecki J, Sycz Z. Com- al. Three-dose vs. extended-course Rev. 2006; 2:CD005360. posite allotransplantations of knee clindamycin prophylaxis for free-flap 1073. Perrotti JA, Castor SA, Perez PC et al. joint, larynx, uterus, abdominal wall, reconstruction of the head and neck. Antibiotic use in aesthetic surgery: a face and penis. Ann Transplant. 2007; Arch Otolaryngol Head Neck Surg. national survey and literature review. 12:5-11. 2003; 129:771-4. Plast Reconstr Surg. 2002; 109:1685-93. 1043. Bonatti H, Brandacher G, Margreiter R 1058. Serletti JM, Davenport MS, Herrera 1074. Smyth AG, Knepil GJ. Prophylactic et al. Infectious complications in three HR et al. Efficacy of prophylactic an- antibiotics and surgery for primary double hand recipients: experience tibiotics in reduction mammoplasty. clefts. Br J Oral Maxillofac Surg. 2008; from a single center. Transplant Proc. Ann Plast Surg. 1994; 33:476-80. 46:107-9. 2009; 41:517-20. 1059. Halpern AC, Leyden JJ, Dzubow LM et 1075. Cocco JF, Antonetti JW, Burns JL et 1044. Babcock MD, Grekin RC. Antibiotic al. The incidence of bacteremia in skin al. Characterization of the nasal, sub- use in dermatologic surgery. Dermatol surgery of the head and neck. J Am lingual and oropharyngeal mucosa Clin. 2003; 21:337-48. Acad Dermatol. 1988; 19:112-6. microbiota in cleft lip and palate indi- 1045. Messingham MJ, Arpey CJ. Updates on 1060. Samra S, Sawh-Martinez R, Barry O et viduals before and after surgical repair. the use of antibiotics in cutaneous sur- al. Complication rates of lipoabdomi- Cleft Palate Craniofac J. 2010; 47:151-5. gery. Dermatol Surg. 2005; 31:1068-78. noplasty versus traditional abdomi- 1046. Wright TI, Baddour LM, Berbari EF et noplasty in high-risk patients. Plast Appendix A—National Healthcare al. Antibiotic prophylaxis in dermato- Reconstr Surg. 2010; 125:683-90. Safety Network criteria for classifying logic surgery: advisory statement 2008. 1061. Olsen MA, Lefta M, Dietz JR et al. Risk 35 J Am Acad Dermatol. 2008; 59:464-73. factors for surgical site infection after wounds 1047. Throckmorton AD, Boughey JC, major breast operation. J Am Coll Surg. Clean: An uninfected operative wound in Boostrom SY et al. Postoperative 2008; 207:326-35. which no inflammation is encountered and the prophylactic antibiotics and surgi- 1062. Dixon AJ, Dixon MP, Dixon JB. respiratory, alimentary, genital, or uninfected cal site infection rates in breast sur- Prospective study of skin surgery in urinary tracts are not entered. In addition, clean gery patients. Ann Surg Oncol. 2009; patients with and without known di- wounds are primarily closed and, if neces- 16:2464-9. abetes. Dermatol Surg. 2009; 35:1035- sary, drained with closed drainage. Operative 1048. Khan UD. Breast augmentation, an- 40. incisional wounds that follow nonpenetrating tibiotic prophylaxis, and infection: 1063. Wahie S, Lawrence CM. Wound com- (blunt) trauma should be included in this cat- comparative analysis of 1,628 primary plications following diagnostic skin bi- egory if they meet the criteria. augmentation mammoplasties assess- opsies in dermatology inpatients. Arch Clean-contaminated: Operative wounds in ing the role and efficacy of antibiotics 2007; 143:1267-71. Dermatol. which the respiratory, alimentary, genital, or uri- prophylaxis duration. Aesthetic Plast 1064. Gravante G, Araco A, Sorge R et al. nary tracts are entered under controlled condi- Surg. 2010; 34:42-7. Wound infections in post-bariatric 1049. Baran CN, Sensöz Ö, Ulusoy MG. patients undergoing body contouring tions and without unusual contamination. Spe- Prophylactic antibiotics in plastic and abdominoplasty: the role of smoking. cifically, operations involving the biliary tract, reconstructive surgery. Plast Reconstr Obes Surg. 2007; 17:1325-31. appendix, vagina, and oropharynx are included Surg. 1999; 103:1561-6. 1065. Rey JE, Gardner SM, Cushing RD. in this category, provided no evidence of infec- 1050. Mekako AI, Chetter IC, Coughlin PA Determinants of surgical site infection tion or major break in technique is encountered. et al., on behalf of the Hull Antibiotic after breast biopsy. Am J Infect Control. Contaminated: Open, fresh, accidental pRophylaxis in varicose VEin Surgery 2005; 33:126-9. wounds. In addition, operations with major Trialists (HARVEST). Randomized 1066. Sevin A, Senen D, Sevin K et al. An- breaks in sterile technique (e.g., open cardiac clinical trial of co-amoxiclav versus no tibiotic use in abdominoplasty: pro- massage) or gross spillage from the gastrointes- antibiotic prophylaxis in varicose vein spective analysis of 207 cases. J Plast tinal tract and incisions in which acute, nonpu- surgery. Br J Surg. 2010; 97:29-36. Reconstr Aesthet Surg. 2007; 60:379-82. rulent inflammation is encountered are included 1051. Stone JF, Davidson JS. The role of an- 1067. Gravante G, Caruso R, Araco A et al. in this category. tibiotics and timing of repair in flexor Infections after plastic procedures: Dirty or infected: Includes old traumatic tendon injuries of the hand. Ann Plast incidences, etiologies, risk factors, and wounds with retained devitalized tissue and Surg. 1998; 40:7-13. antibiotic prophylaxis. Aesthetic Plast those that involve existing clinical infection or 1052. LeRoy J, Given KS. Wound infection Surg. 2008; 32:243-51. perforated viscera. This definition suggests that in breast augmentation: the role of 1068. Bertin ML, Crowe J, Gordon SM. De- the organisms causing postoperative infection prophylactic perioperative antibiotics. terminants of surgical site infection were present in the operative field before the Aesthetic Plast Surg. 1991; 15:303-5. after breast surgery. Am J Infect Control. 1053. Stewart KJ, Stewart DA, Coghlan B et 1998; 26:61-5. operation. al. Complications of 278 consecutive 1069. Harness NG, Inacio MC, Pfeil FF et al. abdominoplasties. J Plast Reconstr Rate of infection after carpal tunnel Appendix B—National Healthcare Aesth Surg. 2006; 59:1152-5. release surgery and effect of antibi- Safety Network criteria for defining a 1054. Rosengren H, Dixon A. Antibacterial otic prophylaxis. J Hand Surg. 2010; surgical-site infection (SSI)8,36 prophylaxis in dermatologic surgery: 35:189-96. an evidence-based review. Am J Clin 1070. Platt R, Zucker JR, Zaleznik DF et al. Superficial incisional SSI: Occurs within 30 Dermatol. 2010; 11:35-44. Perioperative antibiotic prophylaxis days postoperatively and involves skin or sub- 1055. Landes G, Harris PG, Lemaine V et and wound infection following breast cutaneous tissue of the incision and at least one al. Prevention of surgical site infec- surgery. J Antimicrob Chemother. 1993; of the following: (1) purulent drainage from the tion and appropriateness of antibiotic 31(suppl B):43-8. superficial incision, (2) organisms isolated from

282 Am J Health-Syst Pharm—Vol 70 Feb 1, 2013 ASHP Report Antimicrobial prophylaxis an aseptically obtained culture of fluid or tissue from the superficial incision, (3) at least one of the following signs or symptoms of infection: pain or tenderness, localized swelling, redness, or heat, and superficial incision is deliberately opened by surgeon and is culture-positive or not cultured (a culture-negative finding does not meet this criterion), and (4) diagnosis of superficial incisional SSI by the surgeon or attending physician. Deep incisional SSI: Occurs within 30 days after the operative procedure if no implant is left in place or within one year if implant is in place and the infection appears to be related to the operative procedure, involves deep soft tissues (e.g., fascial and muscle layers) of the incision, and the patient has at least one of the following: (1) purulent drainage from the deep incision but not from the organ/space component of the surgical site, (2) a deep incision spontaneously dehisces or is deliberately opened by a surgeon and is culture-positive or not cultured and the patient has at least one of the following signs or symptoms: fever (>38 °C) or localized pain or tenderness (a culture-negative finding does not meet this criterion), (3) an abscess or other evidence of infection involving the deep incision is found on direct examination, during reoperation, or by histopathologic or radiologic examination, and (4) diagnosis of a deep incisional SSI by a surgeon or attending physician. Organ/space SSI: Involves any part of the body, excluding the skin incision, fascia, or muscle layers, that is opened or manipulated during the operative procedure. Specific sites are assigned to organ/space SSI to further identify the location of the infection (e.g., endocarditis, endometritis, mediastinitis, vaginal cuff, and osteomyelitis). Organ/space SSI must meet the following criteria: (1) infection occurs within 30 days after the operative procedure if no implant is in place or within 1 year if implant is in place and the infection appears to be related to the operative procedure, (2) infection involves any part of the body, excluding the skin incision, fascia, or muscle layers, that is opened or manipulated during the operative procedure, and (3) the patient has at least one of the following: (a) purulent drainage from a drain that is placed through a stab wound into the organ/ space, (b) organisms isolated from an aseptically obtained culture of fluid or tissue in the organ/ space, (c) an abscess or other evidence of infection involving the organ/space that is found on direct examination, during reoperation, or by histopathologic or radiologic examination, and (d) diagnosis of an organ/space SSI by a surgeon or attending physician.

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