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Instructions 1. Review the stated learning objectives at the beginning of the CME article and determine if these objectives match your individual learning needs. cme 2. Read the article carefully. Do not neglect the tables ARTICLE and other illustrative materials, as they have been selected to enhance your knowledge and understanding. 3. The following quiz questions have been designed to provide a useful link between the CME article in the issue and your everyday practice. Read each question, choose Vancomycin Prophylaxis of the correct answer, and record your answer on the CME Registration Form at the end of the quiz. 4. Type or print your full name and address and your date of birth in the space provided on the CME Registration Form. Surgical Site in 5. Indicate the total time spent on the activity (reading article and completing quiz). Forms and quizzes cannot be processed if this section is incomplete. All participants are required by the accreditation agency to attest to the time spent Clean Orthopedic completing the activity. 6. Complete the Evaluation portion of the CME Regi­stration Form. Forms and quizzes cannot be processed if the Evaluation Wajdi W. Kanj, BS; John M. Flynn, MD; David A. Spiegel, MD; portion is incomplete. The Evaluation portion of the CME Registration Form will be separated from the quiz upon receipt at John P. Dormans, MD; Keith D. Baldwin, MD, MPH, MSPT Orthopedics. Your evaluation of this activity will in no way affect the scoring of your quiz. 7. Send the completed form, with your $15 payment (check or money order in US dollars drawn on a US bank, or credit educational objectives card information) to: Orthopedics CME Quiz, PO Box 36, Thorofare, NJ 08086, OR take the quiz online. Visit www. As a result of reading this article, should be able to: Healio.com/EducationLab/Orthopedics for details. 8. Your answers will be graded, and you will be advised 1. Identify the motivation for vancomycin prophylaxis in clean orthopedic whether you have passed or failed. Unanswered questions will be considered incorrect. A score of at least 80% is required to pass. surgery. If a passing score is achieved, Keck School of of USC will issue an AMA PRA Category 1™ certificate within 4-6 weeks. 2. Identify the complications and challenges surrounding vancomycin pro- 9. Be sure to mail the CME Registration Form on or before the deadline listed. After that date, the quiz will close. CME phylaxis in clean orthopedic surgery. Registration Forms received after the date listed will not be processed. 3. Describe the effectiveness of intravenous vancomycin in clean orthopedic CME ACCREDITATION This activity has been planned and implemented surgery. in accordance with the Essential Areas and policies of the Accreditation Council for Continuing through 4. Describe the effectiveness of locally delivered vancomycin in clean ortho- the sponsorship of Keck School of Medicine of USC and Orthopedics. Keck School of Medicine of USC is accredited pedic surgery. by the ACCME to provide continuing medical education for physicians. Keck School of Medicine of USC designates this Journal- based CME activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate entity using antibiotics known to be effec- with the extent of their participation in the activity. Abstract This CME activity is primarily targeted to orthopedic tive against MRSA. The goal of this study , hand surgeons, head and neck surgeons, trauma Community-acquired methicillin-resistant was to assess the use of MRSA prophy- surgeons, physical medicine specialists, and rheumatologists. Staphylococcus aureus (MRSA) has been There is no specific background requirement for participants laxis to determine whether it is safe and taking this activity. recognized as a concern FULL DISCLOSURE POLICY effective. In accordance with the Accreditation Council for Continuing since the mid-1990s. Because of the in- Medical Education’s Standards for Commercial Support, all crease in reports of this pathogen, it has A systematic search of the literature was CME providers are required to disclose to the activity audience the relevant financial relationships of the planners, teachers, become increasingly tempting for clini- performed to identify articles that ex- and authors involved in the development of CME content. An individual has a relevant financial relationship if he or she has cians to provide prophylaxis against this amined the use of vancomycin in clean a financial relationship in any amount occurring in the last 12 months with a commercial interest whose products or services are discussed in the CME activity content over which the individual has control. Drs Kanj and Spiegel have no relevant financial relationships The authors are from the Department of Orthopaedic Surgery, the Children’s of to disclose. Dr Flynn receives royalties from Biomet. Dr Philadelphia, Philadelphia, Pennsylvania. Dormans is a board member of POSNA and receives royalties The material presented in any Keck School of Medicine of USC continuing education activity does not from Elsevier, Mosby, Brooke’s Publishing, and his department receives grants from AO Spine and OMEGA. Dr Baldwin is a necessarily reflect the views and opinions of Orthopedics or Keck School of Medicine of USC. Neither stock owner in Pfizer. Dr Aboulafia, CME Editor, has no relevant Orthopedics nor Keck School of Medicine of USC nor the authors endorse or recommend any tech- financial relationships to disclose. Dr D’Ambrosia, Editor-in- niques, commercial products, or manufacturers. The authors may discuss the use of materials and/or prod- Chief, has no relevant financial relationships to disclose. The staff of Orthopedics have no relevant financial relationships ucts that have not yet been approved by the US Food and Drug Administration. All readers and continuing to disclose. education participants should verify all information before treating patients or using any product. UNLABELED AND INVESTIGATIONAL USAGE Correspondence should be addressed to: Keith D. Baldwin, MD, MPH, MSPT, Department of The audience is advised that this continuing medical Orthopaedic Surgery, The Children’s Hospital of Philadelphia, 34th and Civic Center Blvd, 2 Wood education activity may contain references to unlabeled uses of FDA-approved products or to products not approved by the Bldg, Philadelphia, PA 19104 ([email protected]). FDA for use in the . The faculty members have doi: 10.3928/01477447-20130122-10 been made aware of their obligation to disclose such usage.

138 ORTHOPEDICS | Healio.com/Orthopedics Vancomycin Prophylaxis in Orthopedic Surgery | Kanj et al cme ARTICLE orthopedic surgery. Infection rates and its transmission and mode of antibiotic nously had effective serum and synovial adverse events were extracted, and the resistance.4 vancomycin levels intraoperatively and in data were aggregated and analyzed using Although the use of vancomycin pro- the knee for more than 20 hours postop- a DerSimonian and Laird random effects phylaxis has seemed to increase, debate eratively. model. Publication bias and study quality remains about whether the drug achieves The purpose of the current systematic were also assessed. No benefit of paren- adequate penetration of relevant tissues to literature review was to determine whether teral administration of vancomycin was justify prophylaxis. Parenteral vancomy- evidence exists supporting the routine use identified. Local, vancomycin-impreg- cin has variable absolute concentra- of vancomycin prophylaxis in the face of nated cement and powder are associated tions and lower bone:serum concentration increasing bacterial resistance in orthope- with lower infection rates. Few adverse ratios in uninfected bone than most other dic surgery. In addition, the study aimed to events occurred, and most of those that antistaphylococcal agents.5 In addition, determine which mode of administration, if occurred involved infusion rate. recent data have shown a concerning trend any, was effective, and what safety profile toward higher infection rates when using vancomycin has as a prophylactic drug in Cost, resistance, and are con- vancomycin to prevent in the clean orthopedic surgery. cerns in using vancomycin in ad- absence of the carrier state.6 dition to standard antibiotic prophylaxis. Although first-generation cephalospo- Search Strategy and Methods Given the lack of efficacy of intravenous rins have been vetted in clinical trials for Medline and EMBASE databases were vancomycin, the authors do not recom- prophylaxis of surgical site infections, searched for articles containing the terms mend its routine use in clean orthopedic no such literature exists for vancomycin. vancomycin AND prophylaxis AND sur- surgery. However, local administration Despite this, vancomycin has been shown gery and vancomycin AND prophylaxis appears to be safe and effective. The data to be safe in the treatment of infections.7 AND orthopedics. References from the ar- are most compelling in orthopedic spine Incidence rates for adverse reactions con- ticles were reviewed to identify additional surgery in which a patient without prophy- sist of the following: an anaphylactoid studies of interest. abstract laxis is more than 4 times as likely to have reaction known as red man syndrome books from the past 3 years available on- a deep postoperative wound infection (5%-50%), (approxi- line were searched to assure that the most compared with a patient who received lo- mately 40%), rash (4%-6%), nephrotoxic- recent data were obtained. Abstracts for the cal vancomycin. The authors recommend ity (7%-8%), proteinuria (approximately Research Society, the American the use of local antibiotics when possible 2%), hepatotoxicity (approximately 2%), Association of Hip and Knee Surgeons, in clean orthopedic surgery. and ototoxicity (4%-10%).7-10 Although the Orthopaedic Trauma Association, antihistamines are used to treat these reac- the European Paediatric Orthopaedic he use of prophylactic antibiotics tions, anaphylaxis, although exceedingly Society, the Pediatric Orthopaedic Society in orthopedic surgery is a well- rare, does not respond to this therapy.10,11 of North America, and the American Taccepted practice. First-generation Vancomycin prophylaxis in clean or- Academy of Orthopaedic Surgeons from cephalosporins have been shown to be thopedic surgery may be administered 2009 to 2011 were also searched. The ab- safe, effective, and superior to placebo either locally or parenterally. Parenteral stract book for the American Orthopaedic in terms of reduction in surgical site in- vancomycin is given prior to incision, Association was available for 2011 fections.1,2 Nafcillin has also been shown similar to standard antibiotic prophy- only, North American Spine Society ab- to be an effective agent for prophylaxis, laxis. Local forms consist of antibiotic- stract books were not available, and the although Staphylococcus aureus organ- impregnated cement typically used in Musculoskeletal Infection Society had isms from the same series were found to adult reconstruction, and powder forms abstracts for 2010 and 2009, but the 2011 be sensitive to penicillin.3 Since the first placed in bone grafts are primarily used abstracts were not posted at the time of recognized case of community-acquired for spine surgery. The elution and con- this review, so the authors were unable to methicillin-resistant S aureus (MRSA) centration of vancomycin following its use these references. Finally, the tables of in the 1990s, an increase in the reports of use in the form of impregnated bone ce- contents of 13 major orthopedics journals these infections has been noted.4 This has ment has been studied in vivo and was from the past 6 months were reviewed. led some clinicians to routinely use van- shown to have variable bioactivity against These reviews were performed because comycin as prophylaxis against surgical Staphylococcus epidermidis, as well as this topic is becoming more popular, and site infections. This practice is controver- variable elution properties.12 Eshkenazi et many of the data are recent. sial because community-acquired MRSA al13 reported that patients who had been Studies were included if they met the differs from hospital-acquired MRSA in given vancomycin prophylaxis intrave- following criteria: (1) English language;

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used 3 groups: a control group, a group “Vancomycin AND prophylaxis “Vancomycin AND prophylaxis that had an alcohol-based preoperative AND surgery” AND orthopedic” 669 results 83 results preparation and drains, and a group that had vancomycin prophylaxis, alcohol- based preparation, and drains. For the Filtered by title Filtered by title 99 results 65 results purpose of analysis, the current authors compared their alcohol drain group with their vancomycin, alcohol, and drain Combined and duplicates removed group to try to isolate the effect of vanco- 109 results mycin powder.

References cross-checked and After data extraction, a DerSimonian search of past 6 months in and Laird random effects model was used orthopedic journals, and abstracts to aggregate infectious data for meta-anal- from specialty meetings 23 results ysis. Data were analyzed separately for all modalities (local [including cement and Filtered using exclusion and powder], systemic, and intravenous). In inclusion criteria 12 results addition, data were analyzed for deep (de- 1 fined in individual studies as intra-articular Figure 1: Flow chart showing the search strategy. infections confirmed with joint cultures, or, for spine patients, infections involving sub- fascial layers and spinal instrumentation) (2) orthopedic patients only or orthopedic (6) other execution issues.14 Each study and superficial (defined in individual stud- patients separable in the body of the text was graded independently by 2 authors of ies as infections involving the superficial or in tables; (3) vancomycin used as sur- the current study (W.W.K., K.D.B.). and subcutaneous tissue, with clini- gical prophylaxis in intravenous, cement, Overall, 8 studies15-22 and 4 ab- cal signs of infection) infections (Table 2). or powder forms; (4) clean (ie, stracts5,23-25 met the criteria for analysis Publication bias was assessed with funnel no vancomycin used for treatment of in- (Table 1). The studies and abstracts in- plots and Egger’s intercepts. fection or for prophylaxis in the case of cluded a total of 10,889 patients.15-22 A Meta-analysis was conducted with open fractures or traumatic arthrotomies); total of 6630 patients received vancomy- MIX version 1.7 software (BiostatXL, and (5) studies with levels of evidence cin prophylaxis, and 4259 were controls. Sunnyvale, California).26 of I through IV. Studies were excluded if A total of 3180 patients were treated they met any of the following criteria: (1) with intravenous vancomycin,18,20,22,23 of Results inclusion criteria were not met; (2) anti- these 168 were treated with vancomycin- Deep and Superficial Infection Rates biotics being used for current infection; impregnated cement as part of a total Intravenous vancomycin added to typi- (3) basic science study; (4) animal model joint ,16,17 3259 with vanco- cal gram-positive coverage was reported in only; (5) editorial, opinion, review, or mycin powder as an adjunct to spine sur- 3 studies of patients undergoing total joint commentary; or (6) combination of van- gery,5,19,21,24,25 and 58 (62 surgeries) with arthroplasty (Figure 2).20,22,23 One case comycin and another antibiotic used in a vancomycin-impregnated hydroxyapa- control study reviewed infection rates in local form for prophylaxis. Search details tite on their noncemented joint replace- spine surgery before and after institution are shown in Figure 1. ments.15 Of these, 2 were primarily safe- of a vancomycin prophylaxis regimen and Study quality was graded using the ty studies, which examined a cohort of found no difference in infection rates.18 No systematic quality assessment described patients treated with either intravenous significant difference was found between by Zaza et al.14 This tool, designed to vancomycin or vancomycin cement.16,20 those treated with intravenous vancomycin provide consistency, reduce bias, and im- These 2 studies did not compare vanco- and those treated with standard prophylaxis prove the validity and reliability of pre- mycin prophylaxis patients with control (P5.380). ventive medicine studies, uses a checklist patients. Another study was a case con- Five studies examined deep infections to evaluate the execution of studies in 6 trol study that compared spine surgery in spine surgery when using a vancomycin- areas: (1) intervention and study descrip- patients with infections with those with- impregnated powder.5,19,21,24,25 These stud- tions, (2) sampling, (3) measurement, (4) out infections (case control) to determine ies showed in the aggregate that a patient analysis, (5) interpretation of results, and rates of vancomycin use.18 Pahys et al25 was more than 4 times as likely to have a

140 ORTHOPEDICS | Healio.com/Orthopedics Vancomycin Prophylaxis in Orthopedic Surgery | Kanj et al cme ARTICLE

Table 1 Study Demographics

Vancomycin Author Year Journal Medium Surgery Type Outcomes LOE Rahman et al5 2011 Scoliosis Research Society Powder Adult spinal deformity Deep infection III Annual Meeting Assor15 2010 Canadian Journal of Powder TKA (noncemented) Superficial and deep II Surgery infection Buttaro et al16 2010 Hip International Cement Revision THA for aseptic Superficial and deep IV failure infection; short-term clinical and radiographic results Chiu & Lin17 2009 Journal of Bone and Joint Cement Revision TKA (cemented) Superficial and deep I Surgery, American Volume infection Klekamp et al18 1999 Journal of Spinal Disorders Intravenous Spinal surgery (various) Superficial and deep III & Techniques infection O’Neill et al19 2011 The Spine Journal Powder Posterior for Superficial and deep II traumatic infection; complications Ritter et al20 1989 Orthopedics Intravenous Bilateral/unilateral total Superficial and deep IV joint arthroplasty infection; complications Sweet et al21 2011 Spine Powder Thoracic and lumbar Superficial and deep II posterior instrumented infection; complications spinal fusions Tyllianakis et al22 2010 Journal of Arthroplasty Intravenous Primary TKA and THA Superficial and deep II infection Smith et al23 2011 American Association of Intravenous Adult joint reconstruction Deep infection III Hip and Knee Surgeons Annual Meeting Molinari et al24 2011 Scoliosis Research Society Powder Adult spinal surgery Deep infection IV Annual Meeting Pahys et al25 2011 American Academy of Powder Cervical spine Deep infection III Orthopaedic Surgeons Annual Meeting Abbreviations: LOE, level of evidence; THA, total hip arthroplasty; TKA, total knee arthroplasty.

deep infection without powder prophylaxis Safety (4%) of 201 patients that returned to baseline than with prophylaxis (P,.001) (Figure 3). Incidence rates for adverse reactions level postoperatively and minor drug infu- O’Neill et al19 examined superficial infec- associated with vancomycin have been sion reactions in 40 (20%) patients: red man tions in spine surgery patients but reported well documented in the scientific literature syndrome (2%), itching (15%), rash (1%), no difference with or without prophylaxis and include the following: an anaphylac- and itching and rash (2%). All complications (P5.239). toid reaction known as red man syndrome responded to antihistamine therapy and none Two studies used vancomycin cement, (5%-50%), thrombophlebitis (approxi- required cessation of drug infusion. The 5 but only 1 was comparative.17 This study mately 40%), rash (4%-6%), nephrotoxic- studies that used local vancomycin powder found a significant decrease in deep in- ity (7%-8%), proteinuria (approximately for spine surgeries reported no adverse ef- fections but not in superficial infections 2%), hepatotoxicity (approximately 2%), fects attributed to the local application of (P5.013 and .492, respectively).17 One and ototoxicity (4%-10%).7-10 Its use as vancomycin, specifically no episodes of hy- study used a mixture of vancomycin in prophylaxis warrants careful precautions potension or renal toxicity.5,19,21,24,25 the hydroxyapatite layer of noncemented to avoid these complications. TKA and reported no difference in deep Only 1 of the 12 studies reported the Vancomycin Levels or superficial infections P( 5.249 and presence of these complications.20 Ritter et Vancomycin levels were measured .999, respectively).15 al20 reported elevated creatinine levels in 8 in the serum of articular fluid in 3 stud-

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of infection with vancomycin to be 20% of Table 2 what it was without vancomycin; this re- Superficial and Deep Infection Criteria sult was statistically significant (P,.01). When all superficial infections were ex- Superficial Infection amined, some evidence of publication bias Author Criteria Deep Infection Criteria was found, with smaller studies showing Rahman et al5 Not defined Deep wound process requiring operative lower infection rates preferentially in the I&D within 90 d of index procedure prophylaxis group compared with the Assor15 Early and localized Intra-articular infection confirmed by nonprophylaxis group (P5.05). The sig- surgical site infections articular fluid culture nificance of this finding is unclear because Buttaro et al16 Not defined Moderate or severe pain; discharging sinus or serum parameters the identification of superficial infections was not a main aim of any study. The fun- Chiu & Lin17 Not defined Intra-articular infection confirmed with CRP, ESR, and articular fluid culture nel plot for vancomycin powder in spine Klekamp et al18 Not defined Spinal wound infections requiring surgery was symmetric, with no evidence operative of publication bias (P5.63). O’Neill et al19 Local infection based on Infection based on axial imaging and wound inspection confirmed with culture Study Quality Ritter et al20 Not defined Not defined The authors were unable to assess Sweet et al21 Infection involving Infection of subfascial layers study quality on the 4 abstracts because superficial skin or and spinal instrumentation not enough information existed. Two of subcutaneous tissues these studies were Level III case controls, Tyllianakis et Local infection based on Intra-articular infection based on acute al22 clinical signs including clinical and radiographic findings, wound and 1 was a Level IV case series. wound drainage drainage, or dehiscence Of the remaining 8 studies, all ad- Smith et al23 Not defined equately described the patient population Molinari et al24 Not defined Not defined and intervention being evaluated. The se- Pahys et al25 Not defined Not defined lection and screening criteria for patient inclusion were clearly described in all but Abbreviations: CRP, C-reactive protein; ESR: erythrocyte sedimentation rate; I&D, 18 irrigation and debridement. 1 study. The entire population was used in all 8 studies, minimizing selection bias. In 1 of the studies, all treatment group patients were operated on by 1 , ies.15,20,21 Assor15 measured the intra- the study by Sweet et al.21 Wound drains whereas all controls were operated on by articular vancomycin concentration in were used as the source for the wound con- different surgeons, which could bias in- 4 patients on postoperative day 3 or 4 centrations, which were a mean of 1457 µg/ fection results through surgical technique, when surgical drains were removed. The mL postoperative day 1 and 128 µg/mL at operative time, or other factors known to concentration was found to be at least 12 postoperative day 3. Serum levels were not influence infection.19 In another study, the times the minimum inhibitory concentra- detectable in 80% of the patients sampled treatment and control groups were sepa- tion in all patients. No long-term or serum and were less than 1.6 µg/mL in the remain- rated by time and were not randomized.21 measurements were performed in this ing 20%.21 In no study were the observers blinded to study. The remaining 8 studies did not measure the intervention. Furthermore, 3 studies Ritter et al20 measured the serum van- serum or local vancomycin concentrations. did not exclude patients with significant comycin concentration in all patients over comorbidities, which could allow con- a 24-hour postoperative period. Peak val- Publication Bias founding but potentially increase the ex- ues occurred at 1 hour postoperatively, The current study’s funnel plots for the ternal validity of their results.16,20,21 One with a mean value of 25.8 µg/mL. Mean question of whether vancomycin was ef- study had longer operative time in the concentration at 24 hours was 4.5 µg/mL, fective (all modalities) found significant control group, which was not controlled still greater than the minimum inhibitory publication bias (P5.02). The publication for to minimize confounding.19 concentration for all sensitive organisms. bias suggests that larger effect sizes were All but 1 study described the antibi- Wound and serum vancomycin concen- shown in smaller studies. However, a trim otic regimens given to the patients pre-, trations were measured in 178 patients in and fill analysis showed the overall odds intra-, and postoperatively (Table 3).18

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2 Figure 2: Forest plot showing no difference in infection rate for intravenous (IV) prophylaxis vs no IV prophylaxis. Abbreviation: CI, confidence interval.

3 Figure 3: Forest plot showing decreased infection rate using powder vancomycin in spine surgery. Abbreviation: CI, confidence interval.

Similarly, 1 study did not report precise economic and social costs for the patient, antibiotics.28,29 This is important because diagnostic criteria for deep and superficial the hospital, and the community. It is es- first-generation cephalosporins have been infections.20 Appropriate statistical testing timated that the costs associated with a widely used as prophylaxis against surgi- was conducted for 6 comparative stud- single postoperative spinal infection are cal site infections for decades. Studies have ies (5 cohort studies and 1 case control more than $100,000.27 The majority of pa- shown these antibiotics to be safe and ef- study).15,17-19,21,22 However, when statisti- tients who sustain these infections never fective for use prior to orthopedic surgery, cal testing was repeated for 1 of the stud- return to work, resulting in indirect loss and they remain the most commonly used ies that claimed to have a difference in the of productivity to society.27 For these rea- and preferred agents for prophylaxis.26 infection rate, no statistically significant sons, much research has been conducted Recently, the emergence of MRSA difference was found.15 to address this issue. and the clear relationship between the na- The rate of hospital- and community- sal carriage of MRSA and postoperative Discussion acquired S aureus infections has been in- surgical site infections has led clinicians Surgical site infections account for creasing worldwide since its discovery in to begin using more selective antibiot- 22% of all –related infections, the 1960s. It has been reported as the re- ics as prophylaxis.30,31 Meanwhile, stud- resulting in an estimated $1 to $10 billion sponsible pathogen in 48.6% of surgical ies in a general surgical population have in additional medical costs annually.26 site infections in orthopedic surgeries, with shown that vancomycin prophylaxis may Postoperative infections carry serious a 56% rate of resistance to beta-lactam increase the rate of infections in patients

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Table 3 Antibiotic Regimens

Study Preoperative Intraoperative Postoperative Rahman et al5 Not defined 500 mg to 1g vancomycin Not defined powder Assor15 500 mg IV cephazolin 1-2 g vancomycin powder 500 mg IV cephazolin mixed with HAC every 12 h for 2 d Buttaro et al16 1 g IV cephazolin Bone graft with 1 g vancomycin 1 g IV cephazolin every 8 h for 24 h powder (3 doses total) Chiu & Lin17 500 mg IV cephazolin and 80 1 g vancomycin powder in 500 mg IV cephazolin every 6 h and 80 mg IV mg IV gentamicin 40 g of cement gentamicin every 12 h for 36 h; followed by 500 mg oral cephazolin every 6 h for 7 d Klekamp et al18 Not described Not described Not described O’Neill et al19 1 g IV cephazolin 1 g vancomycin powder 1 g IV cephazolin every 8 h for 24 h (3 doses total) Ritter et al20 1 g IV vancomycin1 None given None given 80 mg gentamicin Sweet et al21 1 g IV cephazolin 1 g vancomycin powder 1 g IV cephazolin every 8 h for 24 h mixed with cement and 1 g (3 doses total) vancomycin powder sprinkled in wound Tyllianakis et al22 Group A, 1.5 g IV cefuroxime; None given Group A, 750 mg IV cefuroxime at 8 and 16 h; group B, 500 mg IV fusidic acid; group B, 500 mg IV fusidic acid at 8 and 16 h; group C, 1 g IV vancomycin group C, 1 g vancomycin at 12 and 24 h Smith et al23 Not defined Not defined Not defined Molinari et al24 Not defined 1 g vancomycin powder Not defined Pahys et al25 Not defined 500 mg vancomycin powder Not defined Abbreviation: IV, intravenous.

who are not carriers.6,32 This is particular- in the case of adult reconstruction, is safe noted for local administration, specifical- ly concerning because S aureus resistance and effective according to the best avail- ly kidney toxicity or red man syndrome. to glycopeptides such as vancomycin has able literature. Parenteral (intravenous) Serum levels of vancomycin with local led some authors to recommend against vancomycin does not appear to be as use- administration are low to nonexistent, ac- nonselective uses of these antibiotics for ful; although studies available on this mo- cording to the best available data.21 The prophylaxis.33,34 dality are limited, the available data sug- effect size of vancomycin powder is asso- The goals of the current systematic gest that it provides no benefit over stan- ciated with a number needed to treat of 46 review were to determine whether vanco- dard prophylaxis.18,20,22 It should be noted (ie, 46 patients would need to be treated mycin prophylaxis, in addition to standard that 3 studies are available on this modality with vancomycin powder to prevent 1 prophylaxis, was effective in decreasing in adult reconstruction,20,22,23 but only 1 in deep postoperative infection). surgical site infections in clean orthope- spine surgery.18 In addition, according to cost data dic surgery in local or parenteral forms; In terms of safety, vancomycin given from the authors’ institution, this inter- whether vancomycin is safe to administer in prophylactic doses appears to be safe vention would cost approximately $2.50 on a prophylactic basis locally or paren- to use in local and parenteral forms.7,8,16,20 per patient. As such, it would cost ap- terally; and the state of the literature to ad- Data from single studies suggest that the proximately $115 to prevent 1 deep spine dress the first and second goals. adverse effects of parenteral vancomycin infection (oral communication, This study found that local vancomycin, were limited to infusion reactions and personnel, The Children’s Hospital of in the form of intrawound powder in the responded to slowed infusion rates and Philadelphia, November 2011). Because case of spine surgery or antibiotic cement antihistamines.20 No adverse effects were the outcome is expensive and life chang-

144 ORTHOPEDICS | Healio.com/Orthopedics Vancomycin Prophylaxis in Orthopedic Surgery | Kanj et al cme ARTICLE ing and the intervention is relatively be- prophylaxis for clean orthopedic surgery. It 5. Rahman RK, Lenke LG, Bridwell KH, et al. Intrawound vancomycin powder lowers nign and inexpensive, the authors feel that may be of benefit in situations where the the acute deep wound infection rate in adult this constitutes a clinically effective and patient is allergic to cefazolin or is a carrier spinal deformity patients. Paper presented at: Scoliosis Research Society 46th Annual cost-effective treatment. In addition, the of MRSA, although few data exist in the Meeting & Course; September 14-17, 2011; abstract that was most favorable toward orthopedic literature to support this. Louisville, KY. intravenous vancomycin for joint replace- However, local vancomycin appears to be 6. Gupta K, Strymish J, Abi-Haidar Y, Williams ment patients had an effect size that would safe and effective to use as additional anti- SA, Itani KM. Preoperative nasal methicillin- resistant Staphylococcus aureus status, surgi- be associated with a number needed to biotic prophylaxis when large prosthetic or cal prophylaxis, and risk-adjusted postop- treat of 161, approximately one-quarter as fixation devices are used. The authors give erative outcomes in veterans. Infect Control efficacious as local treatment. In the best the use of vancomycin powder a U.S. Hosp Epidemiol. 2011; 32(8):791-796. case, given data from the authors’ institu- Preventive Services Task Force level B rec- 7. Sorrell TC, Collignon PJ. A prospective study of adverse reactions associated with van- tion, this would represent $9581 per in- ommendation: the benefits outweigh the comycin therapy. J Antimicrob Chemother. fection saved (oral communication, phar- risks, and the data are consistent and com- 1985; 16(2):235-241. macy personnel, The Children’s Hospital pelling. In addition, pilot data from an in- 8. Mellor JA, Kingdom J, Cafferkey M, of Philadelphia, November 2011). If the formal survey performed of major spine Keane CT. Vancomycin toxicity: a prospec- tive study. J Antimicrob Chemother. 1985; full systematic review is to be believed, centers suggests that this method is becom- 15(6):773-780. no benefit over standard treatment would ing the standard of care in the spine com- 9. Savarese A, Nanni ML, Pasquali C, Egidio exist. munity (oral communication, J.P. Dormans, AC. Vancomycin prophylaxis in joint arthro- plasty. Chir Organi Mov. 1999; 84(3):247- Limitations of this systematic review MD, The Children’s Hospital of 251. include a low level of evidence and scien- Philadelphia, November 2011). Further 10. Wazny LD, Daghigh B. Desensitization pro- tific rigor inherent in the included studies. study is warrented on this particular modal- tocols for vancomycin hypersensitivity. Ann None of the studies were well-designed, ity. It is unclear whether this is specifically Pharmacother. 2001; 35(11):1458-1464. randomized, placebo-controlled, double- vancomycin providing the increased pro- 11. Kupstaite R, Baranauskaite A, Pileckyte M, Sveikata A, Kadusevicius E, Muckiene G. blind trials. The member studies had is- tection or whether local antibiotics provide Severe vancomycin-induced anaphylactic re- sues with selection bias and observer bias a locally inhospitable environment for bac- action. Medicina (Kaunas). 2010; 46(1):30- outlined in the quality analysis. In addi- teria. Gentamicin was used by Borkhuu et 33. tion, publication bias may have existed, as al35 in neuromuscular spinal fusions with 12. Brien WW, Salvati EA, Klein R, Brause B, Stern S. Antibiotic impregnated indicated by our Egger’s intercept for all similar results. The current authors recom- in total hip arthroplasty. An in vivo compari- modalities and superficial infections. This mend further safety and clinical data to son of the elution properties of tobramycin and vancomycin. Clin Orthop Relat Res. is unclear because no publication bias was study local vancomycin in clean orthope- 1993; (296):242-248. detected in deep infections in the indi- dic surgery because it appears to provide 13. Eshkenazi AU, Garti A, Tamir L, Hendel D. vidual cohorts, which are more clinically the most consistent protection and is Serum and synovial vancomycin concentra- significant and less heterogeneous. The achieving widespread use. tions following prophylactic administration in knee arthroplasty. Am J Knee Surg. 2001; search method was systematic; however, 14(4):221-223. the search was limited to studies available References 14. Zaza S, Wright-De Aguero LK, Briss PA, et in the English language and indexed in 1. Hill C, Flamant R, Mazas F, Evrard J. al. Data collection instrument and procedure the medical literature. This may increase Prophylactic cefazolin versus placebo in to- for systematic reviews in the guide to com- tal . Report of a multicentre munity preventive services. Am J Prev Med. study quality by increasing the peer re- double-blind randomised trial. Lancet. 1981; 2000; 18(1):44-74. 1(8224):795-796. view rigor to which the studies were sub- 15. Assor M. Noncemented total knee arthro- jected. However, it may also decrease the 2. Doyon F, Evrard J, Mazas F, Hill C. Long- plasty with a local prophylactic anti-infection total number of studies and overestimate term results of prophylactic cefazolin versus agent: a prospective series of 135 cases. Can placebo in total hip replacement. Lancet. J Surg. 2010; 53(1):47-50. effects due to publication bias. 1987; 1(8537):860. 16. Buttaro MA, Guala AJ, Comba F, Suarez 3. Boyd RJ, Burke JF, Colton T. A double-blind F, Piccaluga F. Incidence of deep infection Conclusion clinical trial of prophylactic antibiotics in in aseptic revision tha using vancomycin- hip fractures. J Bone Joint Surg Am. 1973; impregnated impacted bone allograft. Hip With the available data, due to the risks 55(6):1251-1258. Int. 2010; 20(4):535-541. of antibiotic resistance and adverse reac- 4. Chen LF, Chastain C, Anderson DJ. 17. Chiu FY, Lin CF. Antibiotic-impregnated ce- tions, the added expense, and the lack of an Community-acquired methicillin-resistant ment in revision total knee arthroplasty. A apparent difference in deep or superficial Staphylococcus aureus skin and soft tis- prospective cohort study of one hundred and sue infections: management and prevention. eighty-three knees. J Bone Joint Surg Am. infection rates, the authors do not recom- Curr Infect Dis Rep. 2011; 13(5):442-450. 2009; 91(3):628-633. mend the use of parenteral vancomycin as

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18. Klekamp J, Spengler DM, McNamara MJ, 24. Molinari WJ, Khera O, Molinari RW. 30. Morange-Saussier V, Giraudeau B, van der Haas DW. Risk factors associated with meth- Prophylactic operative site powdered vanco- Mee N, Lermusiaux P, Quentin R. Nasal car- icillin-resistant staphylococcal wound infec- mycin and postoperative deep spinal wound riage of methicillin-resistant Staphylococcus tion after spinal surgery. J Spinal Disord. infection: 1,512 consecutive surgical cases aureus in . Ann Vasc Surg. 1999; 12(3):187-191. during a six-year period. Paper presented 2006; 20(6):767-772. 19. O’Neill KR, Smith JG, Abtahi AM, et al. at: Scoliosis Research Society 46th Annual 31. Kim DH, Spencer M, Davidson SM, et Reduced surgical site infections in patients Meeting & Course; September 14-17, 2011; al. Institutional prescreening for detec- undergoing posterior spinal stabilization of Louisville, KY. tion and eradication of methicillin-resistant traumatic injuries using vancomycin powder. 25. Pahys J, Pahys JR, Cho SK, et al. Methods to Staphylococcus aureus in patients undergo- Spine J. 2011; 11(7):641-646. decrease post-operative infections following ing elective orthopaedic surgery. J Bone Joint Surg Am 20. Ritter MA, Barzilauskas CD, Faris PM, posterior cervical spine surgery. American . 2010; 92(9):1820-1826. Keating EM. Vancomycin prophylaxis and Academy of Orthopaedic Surgeons 2011 32. Antimicrobial prophylaxis in surgery. Med elective total joint arthroplasty. Orthopedics. Annual Meeting; February 15-19, 2011; San Lett Drugs Ther. 2001; 43(1116-1117):92- 1989; 12(10):1333-1336. Diego, CA. 97. 21. Sweet FA, Roh M, Sliva C. Intrawound ap- 26. Evans RP. Surgical site infection prevention 33. Baiocchi P, Capone A, Carfagna P, Santini J Bone plication of vancomycin for prophylaxis in and control: an emerging paradigm. C, Venditti M. Changes in susceptibilities to Joint Surg Am instrumented thoracolumbar fusions: effica- . 2009; 91 suppl 6:2-9. teicoplanin, vancomycin and other antibiot- cy, drug levels, and patient outcomes. Spine 27. Calderone RR, Garland DE, Capen DA, ics among Staphylococcus aureus isolates (Phila Pa 1976). 2011; 36(24):2084-2088. Oster H. Cost of medical care for postopera- in a tertiary-care university hospital. Int J Orthop Clin North Am Antimicrob Agents 22. Tyllianakis ME, Karageorgos A, Marangos tive spinal infections. . . 1996; 7(2):93-96. MN, Saridis AG, Lambiris EE. Antibiotic 1996; 27(1):171-182. 34. Johnson AP, Uttley AH, Woodford N, George prophylaxis in primary hip and knee arthro- 28. Hidron AI, Edwards JR, Patel J, et al. NHSN RC. Resistance to vancomycin and teico- plasty: comparison between cefuroxime and annual update: antimicrobial-resistant patho- planin: an emerging clinical problem. Clin two specific antistaphylococcal agents. J gens associated with healthcare-associated Microbiol Rev. 1990; 3(3):280-291. Arthroplasty . 2010; 25(7):1078-1082. infections: annual summary of data reported 35. Borkhuu B, Borowski A, Shah SA, Littleton 23. Smith EB, Wynne R, Liu H, Good RP. Time to the National Healthcare Safety Network AG, Dabney KW, Miller F. Antibiotic-loaded to include vancomycin for routine periop- at the Centers for Disease Control and allograft decreases the rate of acute deep Infect Control Hosp erative antibiotic prophylaxis in total joint Prevention, 2006-2007. wound infection after spinal fusion in ce- Epidemiol replacement patients? American Association . 2008; 29(11):996-1011. rebral palsy. Spine (Phila Pa 1976). 2008; of Hip and Knee Surgeons 23rd Annual 29. Boucher HW, Corey GR. Epidemiology of 33(21):2300-2304. Meeting; November 8-10, 2011; Dallas, TX. methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2008;46 suppl 5:S344-S349.

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