734 ASHP Therapeutic Guidelines Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery These guidelines were developed jointly by the American evidence base are noted within each individual procedure Society of Health-System Pharmacists (ASHP), the section of the guidelines. Published guidelines with recom- Infectious Diseases Society of America (IDSA), the Surgical mendations by experts in a procedure area (e.g., American Infection Society (SIS), and the Society for Healthcare College of Obstetricians and Gynecologists [ACOG]) and Epidemiology of America (SHEA). This work represents noted general guidelines (e.g., Centers for Disease Control an update to the previously published ASHP Therapeutic and Prevention [CDC], Scottish Intercollegiate Guidelines Guidelines on Antimicrobial Prophylaxis in Surgery,1 as well Network, Medical Letter, SIS, SHEA/IDSA) were also con- as guidelines from IDSA and SIS.2,3 The guidelines are in- sidered.2,3,5–11 tended to provide practitioners with a standardized approach Recommendations for the use of antimicrobial pro- to the rational, safe, and effective use of antimicrobial agents phylaxis are graded according to the strength of evidence for the prevention of surgical-site infections (SSIs) based on available. The strength of evidence represents only support currently available clinical evidence and emerging issues. for or against prophylaxis and does not apply to the antimi- Prophylaxis refers to the prevention of an infection crobial agent, dose, or dosage regimen. Studies supporting and can be characterized as primary prophylaxis, secondary the recommendations for the use of antimicrobial therapy prophylaxis, or eradication. Primary prophylaxis refers to were classified as follows: the prevention of an initial infection. Secondary prophylaxis refers to the prevention of recurrence or reactivation of a • Level I (evidence from large, well-conducted, ran- preexisting infection. Eradication refers to the elimination domized, controlled clinical trials or a meta-analysis) of a colonized organism to prevent the development of an • Level II (evidence from small, well-conducted, ran- infection. These guidelines focus on primary perioperative domized, controlled clinical trials) prophylaxis. • Level III (evidence from well-conducted cohort stud- ies) Guidelines Development and Use • Level IV (evidence from well-conducted case–control studies) Members of ASHP, IDSA, SIS, and SHEA were appointed • Level V (evidence from uncontrolled studies that were to serve on an expert panel established to ensure the valid- not well conducted) ity, reliability, and utility of the revised guidelines. The work • Level VI (conflicting evidence that tends to favor the of the panel was facilitated by faculty of the University of recommendation) Pittsburgh School of Pharmacy and University of Pittsburgh • Level VII (expert opinion or data extrapolated from Medical Center Drug Use and Disease State Management evidence for general principles and other procedures) Program who served as contract researchers and writers for the project. Panel members and contractors were required This system has been used by the Agency for to disclose any possible conflicts of interest before their ap- Healthcare Research and Quality, and ASHP, IDSA, SIS, pointment and throughout the guideline development pro- and SHEA support it as an acceptable method for organizing cess. Drafted documents for each surgical procedural section strength of evidence for a variety of therapeutic or diagnostic were reviewed by the expert panel and, once revised, were recommendations.4 Each recommendation was categorized available for public comment on the ASHP website. After ad- according to the strength of evidence that supports the use ditional revisions were made to address reviewer comments, or nonuse of antimicrobial prophylaxis as category A (levels the final document was approved by the expert panel and the I–III), category B (levels IV–VI), or category C (level VII). boards of directors of the above-named organizations. When higher-level data are not available, a category C recommendation represents a consensus of expert panel Strength of Evidence and Grading of Recommendations. members based on their clinical experience, extrapola- The primary literature from the previous ASHP Therapeutic tion from other procedures with similar microbial or other Guidelines on Antimicrobial Prophylaxis in Surgery1 was clinical features, and available published literature. In these reviewed together with the primary literature published be- cases, the expert panel also extrapolated general principles tween the date of the previous guidelines, 1999, and June and evidence from other procedures. Some recommenda- 2010, identified by searches of MEDLINE, EMBASE, and tions include alternative approaches in situations in which the Cochrane Database of Systematic Reviews. Particular panel member opinions were divided. attention was paid to study design, with greatest credence A major limitation of the available literature on anti- given to randomized, controlled, double-blind studies. microbial prophylaxis is the difficulty in establishing sig- There is a limited number of adequately powered random- nificant differences in efficacy between prophylactic antimi- ized controlled trials evaluating the efficacy of antimicrobial crobial agents and controls (including placebo, no treatment, prophylaxis in surgical procedures. Guidelines development or other antimicrobial agents) due to study design and low included consideration of the following characteristics: va- SSI rates for most procedures. A small sample size increases lidity, reliability, clinical applicability, flexibility, clarity, the likelihood of a Type II error; therefore, there may be no and a multidisciplinary nature as consistent with ASHP’s apparent difference between the antimicrobial agent and pla- philosophy on therapeutic guidelines.4 The limitations of the cebo when in fact the antimicrobial has a beneficial effect.12 ASHP Therapeutic Guidelines 735 A valid study is placebo controlled and randomized with a These guidelines reflect current knowledge of antimi- sufficient sample in each group to avoid a Type II error. Of crobial prophylaxis in surgery. Given the dynamic nature of note, prophylaxis is recommended in some cases due to the scientific information and technology, periodic review, up- severity of complications of postoperative infection (e.g., dating, and revisions are to be expected. an infected device that is not easily removable) necessitat- ing precautionary measures despite the lack of statistical Special Patient Populations. Pediatric patients. Pediatric support. patients undergo a number of procedures similar to adults that may warrant antimicrobial prophylaxis. Although pedi- Summary of Key Updates. These guidelines reflect sub- atric-specific prophylaxis data are sparse, available data have stantial changes from the guidelines published in 1999.1 been evaluated and are presented in some of the procedure- Highlights of those changes are outlined here. specific sections of these guidelines. Selection of antimi- Preoperative-dose timing. The optimal time for admin- crobial prophylactic agents mirrors that in adult guidelines, istration of preoperative doses is within 60 minutes before with the agents of choice being first- and second-generation surgical incision. This is a more-specific time frame than cephalosporins, reserving the use of vancomycin for patients the previously recommended time, which was “at induction with documented b-lactam allergies.19,20 While the use of a of anesthesia.” Some agents, such as fluoroquinolones and penicillin with a b-lactamase inhibitor in combination with vancomycin, require administration over one to two hours; cefazolin or vancomycin and gentamicin has also been stud- therefore, the administration of these agents should begin ied in pediatric patients, the number of patients included in within 120 minutes before surgical incision. these evaluations remains small.20–23 As with adults, there is Selection and dosing. Information is included regard- little evidence supporting the use of vancomycin, alone or ing the approach to weight-based dosing in obese patients in combination with other antimicrobials, for routine peri- and the need for repeat doses during prolonged proce- operative antimicrobial prophylaxis in institutions that have dures.13–18 Obesity has been linked to an increased risk for a high prevalence of methicillin-resistant Staphylococcus SSI. The pharmacokinetics of drugs may be altered in obese aureus (MRSA). Vancomycin may be considered in children patients, so dosage adjustments based on body weight may known to be colonized with MRSA and, in one retrospective be warranted in these patients. For all patients, intraopera- historical cohort study, was shown to decrease MRSA infec- tive redosing is needed to ensure adequate serum and tis- tions.21 Mupirocin use has been studied in and is efficacious sue concentrations of the antimicrobial if the duration of in children colonized with MRSA, but there are limited data the procedure exceeds two half-lives of the drug or there supporting its use perioperatively.24–30 However, there is is excessive blood loss during the procedure (Table 1). little reason to think that the impact and effect would be any Recommendations for selection of antimicrobial agents for different in children, so its use may be justified. Additional specific surgical procedures and alternative agents (e.g.,