Institutional Prescreening for Detection and Eradication of

Transcription

1 This is an enhance PDF from The Journal of Bone an Joint Surgery The PDF of the article you requeste follows this cover page. Institutional Prescreening for Detection an Eraication of Methicillin-Resistant Staphylococcus aureus in Patients Unergoing Elective Orthopaeic Surgery Davi H. Kim, Maureen Spencer, Susan M. Davison, Ling Li, Jeremy D. Shaw, Diane Gulczynski, Davi J. Hunter, Juli F. Martha, Geral B. Miley, Stephen J. Parazin, Pamela Dejoie an John C. Richmon J Bone Joint Surg Am. 2010;92: publishe Jul 7, 2010; oi: /jbjs.i This information is current as of August 5, 2010 Commentary Reprints an Permissions Publisher Information Click here to orer reprints or request permission to use material from this article, or locate the article citation on jbjs.org an click on the [Reprints an Permissions] link. The Journal of Bone an Joint Surgery 20 Pickering Street, Neeham, MA

2 1820 COPYRIGHT Ó 2010 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED A commentary by Bassam A. Masri, MD, FRCSC, is available at an as supplemental material to the online version of this article. Institutional Prescreening for Detection an Eraication of Methicillin-Resistant Staphylococcus aureus in Patients Unergoing Elective Orthopaeic Surgery By Davi H. Kim, MD, Maureen Spencer, RN, Susan M. Davison, MD, Ling Li, MSPH, Jeremy D. Shaw, BA, Diane Gulczynski, RN, Davi J. Hunter, MD, PhD, Juli F. Martha, MPH, Geral B. Miley, MD, Stephen J. Parazin, MD, Pamela Dejoie, an John C. Richmon, MD Investigation performe at New Englan Baptist Hospital, Boston, Massachusetts Backgroun: Surgical site infection has been ientifie as one of the most important preventable sources of morbiity an mortality associate with meical treatment. The purpose of the present stuy was to evaluate the feasibility an efficacy of an institutional prescreening program for the preoperative etection an eraication of both methicillinresistant an methicillin-sensitive Staphylococcus aureus in patients unergoing elective orthopaeic surgery. Methos: Data were collecte prospectively uring a single-center stuy. A universal prescreening program, employing rapi polymerase chain reaction analysis of nasal swabs followe by an eraication protocol of intranasal mupirocin an chlorhexiine showers for ientifie carriers, was implemente. Surgical site infection rates were calculate an compare with a historical control perio immeiately preceing the start of the screening program. Results: During the stuy perio, 7019 of 7338 patients unerwent preoperative screening before elective surgery, for a successful screening rate of 95.7%. One thousan five hunre an eighty-eight (22.6%) of the patients were ientifie as Staphylococcus aureus carriers, an 309 (4.4%) were ientifie as methicillin-resistant Staphylococcus aureus carriers. A significantly higher rate of surgical site infection was observe among methicillin-resistant Staphylococcus aureus carriers (0.97%; three of 309) compare with noncarriers (0.14%; seven of 5122) (p = ). Although a higher rate of surgical site infection was also observe among methicillin-sensitive Staphylococcus aureus carriers (0.19%; three of 1588) compare with noncarriers, this ifference i not achieve significance (p = 0.709). Overall, thirteen cases of surgical site infection were ientifieuring the stuy perio, for an institutional infection rate of 0.19%. This rate was significantly lower than that observeuring the control perio (0.45%; twenty-four cases of surgical site infection among 5293 patients) (p = ). Conclusions: Implementation of an institution-wie prescreening program for the ientification an eraication of methicillin-resistant an methicillin-sensitive Staphylococcus aureus carrier status among patients unergoing elective orthopaeic surgery is feasible an can lea to significant reuctions in postoperative rates of surgical site infection. Level of Evience: Therapeutic Level III. See Instructions to Authors for a complete escription of levels of evience. Disclosure: The authors i not receive any outsie funing or grants in support of their research for or preparation of this work. One or more of the authors, or a member of his or her immeiate family, receive, in any one year, payments or other benefits in excess of $10,000 (DePuy-Mitek, Stryker, LifeNet, Serica, an Axial Biotech) an less than $10,000 (DePuy an Allen Meical) or a commitment or agreement to provie such benefits from a commercial entity. J Bone Joint Surg Am. 2010;92: oi: /jbjs.i.01050

3 1821 Staphylococcus aureus is consiere to be the most important pathogen in terms of surgical site infection. Epiemiologic stuies have emonstrate that most cases of surgical site infection are cause by strains of Staphylococcus aureus that are brought into the hospital environment by patients themselves; i.e., most patients who evelop a Staphylococcus aureus surgical site infection are carriers of the strains causing the infection. The anterior nares may be the most common niche for Staphylococcus aureus among carriers, an multiple stuies have establishe that nasal carrier status is a significant risk factor for the evelopment of surgical site infection with Staphylococcus aureus 1. Methicillin-resistant forms of Staphylococcus aureus are particularly virulent an are especially of concern for a number of reasons. Specifically, methicillin-resistant Staphylococcus aureus has been associate with higher rates of morbiity an mortality following infection 2,thesebacteria can survive on inanimate surfaces an in ry environments for as long as twenty ays 3, an the overall prevalence of methicillin-resistant Staphylococcus aureus appears to be increasing 4. Increase morbiity associate with surgical site infection translates irectly into increase costs associate with meical care. On the average, surgical site infection is associate with a two-week increase in hospital stay, ouble the rate of rehospitalization, an triple the overall cost of treatment 5. Moreover, most capitate payor systems consier surgical site infection to be a preventable complication ano not provie hospitals aitional payment to cover treatment costs, further increasing the financial buren of this complication on institutions. Multiple stuies have ientifie nasal carriage status of Staphylococcus aureus as the most important risk factor for the evelopment of a surgical site infection. The rate of surgical site infection appears to be two to nine times higher in carriers than in noncarriers 1,6,7. In cases of surgical site infection, Staphylococcus aureus isolates have been reporte to match those from the nares 85% of the time 8. One stuy ientifie nasal carriage of Staphylococcus aureus as the only inepenent risk factor for the evelopment of surgical site infection following orthopaeic implant surgery 9. Comparable finings have been reporte in the fiels of cariac an vascular surgery 10,11. Intranasal mupirocin is currently the most efficient metho of eraicating intranasal Staphylococcus aureus an appears to be successful for a majority of treate carriers 8. Multiple clinical stuies have emonstrate efficacy in reucing the rate of Staphylococcus aureus infection in ifferent patient populations, incluing ialysis, cariac, an orthopaeic surgery patients 8, The purpose of the present stuy was to evaluate the feasibility an efficacy of an institution-wie prescreening program for the ientification of Staphylococcus aureus carrier status an eraication of Staphylococcus aureus nasal colonization among patients unergoing elective orthopaeic surgery. The hypothesis was that successful implementation of such a program woul significantly ecrease the institutional rate of surgical site infection. Materials an Methos Stuy Design an Patient Population This prospective clinical stuy receive institutional review boar approval. We evaluate aults unergoing elective inpatient orthopaeic surgery at a single institution between July 2006 an September Eligible proceures inclue arthroplasty, spine, an sports meicine proceures requiring at least one overnight hospital stay. A consecutive series of all patients unergoing elective orthopaeic surgery uring that interval participate in the present stuy. The rates of surgical site infection uring the stuy perio were compare with those observeuring a control perio immeiately preceing implementation of the screening program (between October 2005 an July 2006). A comparison of the two patient populations inicate that basic emographic variables were comparable (Table I). Stuy Intervention: Screening an Eraication Protocol In vitro antibiotic susceptibility testing of all culture isolates was performe accoring to methos recommene by the National Committee for Clinical Laboratory Stanars 19. Nasal cultures were performe by swabbing a sterile saline solutionmoistene polyester (Dacron) swab for five secons along the interior walls of each naris. All culture specimens were obtaine by a eicate technician who ha been initially traine an subsequently supervise by a microbiology supervisor. Rapi preoperative screening of patients with use of a polymerase chain reaction-baseiagnostic test (Cephei, Sunnyvale, California) was use to ientify methicillin-resistant Staphylococcus aureus carriers. Stanar microbiologic culture methos were use to ientify methicillin-sensitive Staphylococcus aureus strains. This institution-wie program was applie to all patients unergoing elective surgery. However, the vast majority of proceures performe at this specialty hospital are TABLE I Demographic Data Stuy Perio (July 2006 to September 2007) Control Perio (October 2005 to July 2006) No. of patients screene Sex (%) Male Female Age* (yr) Male Female *The values are given as the mean.

4 1822 orthopaeic in nature, an the current analysis focuses on the elective orthopaeic surgery experience. Patients who teste positive for either methicillinresistant or methicillin-sensitive Staphylococcus aureus were manage with intranasal 2% mupirocin ointment (Bactroban; GlaxoSmithKline, Milesex, Unite Kingom), which was applie to the interior of each naris twice aily for five ays, an a shower wash with 2% chlorhexiine (Hibiclens; Mölnlycke Health Care, Norcross, Georgia), which was performe once aily for five ays. The polymerase chain reaction test was then repeate to confirm eraication of the carrier status. Initial telephone contacts by traine hospital personnel provieirect personalize eucation an instruction regaring the importance of carrier status an proper implementation of the eraication protocol. A followup telephone call that was mae several ays later to confirm appropriate treatment was critical to achieving a high level of compliance. Patients in whom the carrier status was eliminatei not unergo isolation precautions while in the hospital but i receive preoperative antibiotic prophylaxis with vancomycin in lieu of routine meication with cefazolin. Patients who continue to emonstrate positive carrier status on follow-up testing were manage with routine methicillinresistant Staphylococcus aureus-isolation precautions in aition to receiving preoperative antibiotic prophylaxis with intravenous vancomycin. Patients who were ientifie as carriers of methicillin-sensitive Staphylococcus aureus were similarly manage with five ays of intranasal mupirocin an three ays of chlorhexiine showers. Follow-up polymerase chain reaction testing was not performe on these iniviuals. If any patient unerwent surgery prior to completion of the five-ay course of mupirocin, treatment was complete following surgery. During the perio of the stuy, no aitional systemic changes in the infection-control protocol were institute. Also, to limit the potential bias that might be introuce by a general increase in the awareness of the risks of surgical site infection an increase aherence to routine infection-control measures, no institutional surgical site infection-relate promotional campaign was performe. Surveillance, Outcomes, an Definitions Surveillance for nosocomial infection has been performe continuously at this institution since October 2005 with use of previously valiate methos 20,21. Healthcare-associate infections were ientifie accoring to criteria recommene by the Centers for Disease Control an Prevention 22,23. A surgical site infection was consiere to be present if one of the following finings was note within thirty ays after the operation: (1) the wounraine purulent material, (2) the wounraine serosanguineous material, the eges of the woun an surrouning tissues were erythematous, an the woun culture yiele a pathogen, or (3) a physician state in the meical recor that the surgical site was infecte. In aition, when non-human tissue-erive implants were use, inpatient proceures were followe postoperatively for a minimum of one year. Stitch abscesses were not consiere to be surgical site infections. Each case ientifie by the infection control manager was then reviewe by the hospital epiemiologist to ensure that the criteria for infection were met. Surgeons participate in a post-ischarge surveillance system on a bimonthly basis that emonstrate 95% participation. Surgeon compliance with the surveillance system was promote by annual reporting of the iniviual infection rates for each surgeon to the hospital creentialing committee. The risk inex evelope by the National Nosocomial Infections Surveillance System was use to preict risk, an stanarize infection ratios were calculate. The primary outcome measure was efine as the overall rate of surgical site infection with Staphylococcus aureus (incluing methicillinresistant Staphylococcus aureus) among all inpatients unergoing surgery. Aitional ata collection inclueemographic information an associate comorbiities. Statistical Analysis The rate of surgical site infection was etermine with use of the number of persons who presente for elective orthopaeic surgery uring the relevant time perio as the enominator. Theprimarycomparisonwasmaebetweentheratesof surgical site infection uring the stuy perio an the control perio. Seconary comparisons were mae between the rates TABLE II Screening Results* No. of Patients No. of Cases of Infection Rate of Surgical Site Infection (per 100) No. of Cases of MSSA Infection No. of Cases of MRSA Infection Patients screene Noncarrier 5122 (73.0%) Carrier (MSSA 1 MRSA) 1897 (27.0%) MSSA carrier 1588 (22.6%) MRSA carrier 309 (4.4%) *MSSA = methicillin-sensitive Staphylococcus aureus, an MRSA = methicillin-resistant Staphylococcus aureus.

5 1823 TABLE III Rates of Surgical Site Infection Accoring to Carrier Status* MRSA Carriers Noncarriers P Value (Fisher Exact Test) MSSA Carriers Noncarriers P Value (Fisher Exact Test) No. of patients No. of cases of surgical site infection (rate) 3 (0.97%) 7 (0.14%) (0.19%) 7 (0.14%) *MRSA = methicillin-resistant Staphylococcus aureus, an MSSA = methicillin-sensitive Staphylococcus aureus. of surgical site infection in methicillin-resistant Staphylococcus aureus carriers an methicillin-sensitive Staphylococcus aureus carriers compare with noncarriers uring the stuy perio. The chi-square test was use unless one or more subgroups was five or fewer, in which case the Fisher exact test was utilize. Source of Funing There was no external funing source for this stuy. Results During the stuy perio, 7019 patients unerwent screening with both the polymerase chain reaction test for methicillin-resistant Staphylococcus aureus an routine cultures for methicillin-sensitive Staphylococcus aureus. Seven thousan three hunre an thirty-eight inpatient surgical proceures were performeuring the same perio, yieling a successful screening rate of 95.7%. Thirteen cases of surgical site infection were ientifie among the 7019 screene patients, for a surgical site infection rate of 0.19% uring the stuy perio (Table II). These cases inclue three infections with methicillin-resistant Staphylococcus aureus in previously ientifie methicillinresistant Staphylococcus aureus carriers an three infections with methicillin-sensitive Staphylococcus aureus in previously ientifie methicillin-sensitive Staphylococcus aureus carriers. Seven infections (incluing one infection with methicillin-resistant Staphylococcus aureus an six infections with methicillinsensitive Staphylococcus aureus) arose in noncarriers an presumably reflect true hospital-acquire infections or failure of the screening culture. Among screene patients, 1588 patients (22.6%) were ientifie as methicillin-sensitive Staphylococcus aureus carriers, an 309 patients (4.4%) were ientifie as methicillin-resistant Staphylococcus aureus carriers. The remaining 5122 patients (73%) were noncarriers. Comparing methicillin-resistant Staphylococcus aureus carriers with noncarriers, there were three cases of surgical site infection (all with methicillin-resistant Staphylococcus aureus) among309 methicillin-resistant Staphylococcus aureus carriers an seven cases of surgical site infection (incluing one infection with methicillin-resistant an six infections with methicillinsensitive Staphylococcus aureus) among the 5122 noncarriers; this ifference in rates was significant (0.97% compare with 0.14%; p = 0.016) (Table III). There were three cases of surgical site infection among 1588 methicillin-sensitive Staphylococcus aureus carriers (0.19%), an, although this rate was also higher than that observe among noncarriers (0.14%), the ifference was not significant (p = 0.709). Surgical site infection rates were compare between the stuy an control perios. During the control perio, twentyfour cases of infection were observe among 5293 inpatient orthopaeic surgery patients, for a rate of 0.45% (Table IV). Therefore, uring the stuy perio, a 59% reuction in the infection rate was observe (p = ). The reuction in the infection rate was relatively greater for methicillin-resistant Staphylococcus aureus-associate surgical site infection (0.06% compare with 0.19%; p = ), which was associate with a threefol reuction, than for methicillin-sensitive Staphylococcus aureus-associate surgical site infection (0.13% compare with 0.26%; p = ), which was associate with a twofol reuction. The majority of ientifie methicillin-resistant Staphylococcus aureus carriers were previously unaware of their carrier status an therefore woul not have receive appropriate antibiotic prophylaxis or isolation precautions. Among ientifie methicillin-resistant Staphylococcus aureus carriers, only eight (2.6%) of 309 patients were aware of their status or ha TABLE IV Comparison of Surgical Site Infection Rates Between Stuy an Control Perios* Stuy Perio (July 2006 to September 2007) Control Perio (October 2005 to July 2006) P Value (Chi-Square Test) No. of cases of MRSA infection (rate) 4 (0.06%) 10 (0.19%) No. of cases of MSSA infection (rate) 9 (0.13%) 14 (0.26%) Total no. of cases of surgical site infection (rate) 13 (0.19%) 24 (0.45%) *MRSA = methicillin-resistant Staphylococcus aureus, an MSSA = methicillin-sensitive Staphylococcus aureus.

6 1824 available meical ocumentation inicating their status as carriers. Of the 309 methicillin-resistant Staphylococcus aureus carriers who were ientifieuring the stuy perio, 85% successfully complete all components of the eraication protocol an were subsequently reteste. Seventy-eight percent of these carriers ha negative results on retesting, whereas 22% were foun to be persistently colonize. During the stuy perio, only one (0.02%) of 5122 patients evelope a methicillinresistant Staphylococcus aureus surgical site infection following a negative screening result. Six (0.12%) of 5122 patients evelope a methicillin-sensitive Staphylococcus aureus surgical site infection following a negative screening result. Discussion The present stuy suggests the potential efficacy of a comprehensive institutional screening an selective treatment program for methicillin-resistant Staphylococcus aureus an methicillin-sensitive Staphylococcus aureus carriers in terms of achieving a significant reuction in the rate of surgical site infection. A polymerase chain reaction-base screening test for methicillin-resistant Staphylococcus aureus allowe for the rapi ientification of carrier status, among patients unergoing elective orthopaeic surgery, uring routine prescreening hospital visits. Ultimately, the screening an treatment program was associate with a 59% reuction in the rate of surgical site infection in comparison with that uring the control time perio. There have been two previously reporte stuies of large institutional efforts to reuce the rates of Staphylococcus aureus or methicillin-resistant Staphylococcus aureus infection in patients unergoing surgery 8,24. Although both stuies yiele essentially negative results, the failure to emonstrate a significant reuction in infection rates appears to have been largely ue to methoological issues. Perl et al. conucte a large ranomize, placebo-controlle, ouble-blin trial of intranasal mupirocin treatment for a group of patients unergoing elective cariothoracic, general, oncologic, gynecologic, or neurosurgical proceures 8.Threethousaneight hunre an sixty-four patients were analyze, an no ifference was observe in the rate of surgical site infection with Staphylococcus aureus between patients manage with mupirocin an those receiving placebo. However, although nasal cultures were performe to etermine carrier status, preoperative screening was not use to ientify carriers prior to surgery, an the primary analysis was therefore performe without regar to carrier status. Among patients who were ientifie as Staphylococcus aureus nasal carriers, mupirocin treatment was actually associate with a significant an nearly 50% reuction in the rate of nosocomial infection with Staphylococcus aureus (4.0% compare with 7.7%). Among nasal carriers, the risk of surgical site infection with Staphylococcus aureus was 4.5 times higher among those receiving placebo compare with those manage with mupirocin (95% confience interval, 2.47 to 8.21; p < 0.001). Therefore, the negative stuy result appears to have been largely ue to the failure to select nasal carriers as the population at risk an the failure to efine the primary stuy question in terms of how treatment might affect the rate of surgical site infection in this target population. The other major stuy, by Harbarth et al., was a large prospective interventional cohort stuy of a universal screening program for methicillin-resistant Staphylococcus aureus 24. A rapi polymerase chain reaction screening test for methicillinresistant Staphylococcus aureus was compare with no screening in a group of 21,754 mixe surgical patients in a crossover stuy esign. Ientifie methicillin-resistant Staphylococcus aureus carriers were manage with intranasal mupirocin an chlorhexiine boy wash. No significant ifference in the rates of surgical site infection with methicillin-resistant Staphylococcus aureus was observe between the screene an unscreene groups. A major problem with the stuy, however, was that the vast majority of patient screening was performe at the time of hospital amission, with a relatively small percentage (12%) of patients unergoing outpatient prescreening prior to amission. Among methicillin-resistant Staphylococcus aureus carriers who were actually ientifie an manage in an outpatient setting prior to amission, there were no infections with methicillin-resistant Staphylococcus aureus. Another important consieration with respect to that stuy is that 57% (fifty-three) of the ninety-three patients who evelope a methicillin-resistant Staphylococcus aureus nosocomial infection following screening were methicillin-resistant Staphylococcus aureus-negative at the time of amission, suggesting an enemic methicillin-resistant Staphylococcus aureus problem affecting the stuy institution. In hospitals without enemic methicillin-resistant Staphylococcus aureus contamination, universal screening protocols woul be expecte to be more effective. In contrast to the finings in the stuy by Harbarth et al. 24, only one patient in the present stuy evelope a methicillin-resistant Staphylococcus aureus-associate surgical site infection following a negative screening result. Three of the four observe cases of methicillin-resistant Staphylococcus aureus-associate surgical site infection occurre in patients who were ientifie as methicillin-resistant Staphylococcus aureus carriers uring the screening process, two of whom faile to emonstrate successful eraication of carrier status following treatment. This relatively low rate of infection in uncolonize patients contrasts with the high (59%) rate of e novo infection observe in the stuy by Harbarth et al. 24. Previous surveillance of our institution i not emonstrate a problem with enemic Staphylococcus aureus or methicillinresistant Staphylococcus aureus contamination, an this ifference in hospital environments likely explains the greater efficacy of screening in our stuy. More recently, a stuy of universal screening an selective ecolonization for Staphylococcus aureus in a population of patients unergoing elective total joint arthroplasty was reporte by Rao et al. 25. That stuy was very similar in esign to the current stuy but ha a much smaller sample size. One hunre an sixty-four (26%) of 636 patients were ientifie as nasal carriers an complete a five-ay course of intranasal mupirocin an chlorhexiine baths. This group was compare

7 1825 with both a concurrent an a historical control population, an an overall reuction in the rate of surgical site infection, from 2.6% to 1.5%, was observe. A basic cost-benefit analysis suggeste a net economic savings for the institution of $231,741 per year. The major limitation of our stuy is the use of historical controls. The potential for confouning was highlighte in a stuy by Kalmeijer et al. from the University of Amsteram 26.In that prospective, ouble-blin, placebo-controlle stuy in which intranasal mupirocin treatment was compare with placebo in patients unergoing orthopaeic surgery with implants, no significant reuction in the rate of surgical site infection was observe, espite successful eraication of intranasal carriage status in 83.5% of patients manage with mupirocin as compare with only 27.8% of those receiving placebo. In their analysis of the possible explanations for the negative result, the investigators pointe to an apparent reuction in the overall rate of surgical site infection uring the stuy perio an suggeste a potential surveillance effect. The existence an strength of such a confouning effect woul have clear implications for the use of historical controls. Nevertheless, espite the limitations inherent in the use of historical controls, we believe that such a stuy esign is reasonable in the setting of an averse event that is relatively rare, as is the case with surgical site infection following orthopaeic implant-associate surgery, particularly when an institution-wie screening program is the intervention uner investigation. Our stuy emonstrates the feasibility of implementing a hospital-wie prescreening program for etecting previously unientifie methicillin-resistant Staphylococcus aureus an methicillin-sensitive Staphylococcus aureus carriers with use of a rapi polymerase chain reaction-base assay. Practically, such a program allows early ientification of methicillin-resistant Staphylococcus aureus-colonize patients, treatment, ajustment of preoperative antibiotic prophylaxis, an early isolation an contact precautions for those who continue to remain colonize with methicillin-resistant Staphylococcus aureus. Treatment of carriers with intranasal mupirocin an chlorhexiine showers also may be associate with a significant ecrease in the rate of surgical site infection, most notably in methicillin-resistant Staphylococcus aureus carriers. However, it must be emphasize in this case that ientification of previously unrecognize methicillin-resistant Staphylococcus aureus carriers an switching of preoperative antibiotic prophylaxis to vancomycin may have playe an important role. Efficacy may require the absence of an enemic Staphylococcus aureus an methicillin-resistant Staphylococcus aureus contamination problem. Finally, espite relatively high compliance with such a program an a reuction in surgical site infection rates, previously ientifie methicillin-resistant Staphylococcus aureus carriers appear to remain at increase risk for eveloping surgical site infection following orthopaeic implant-associate surgery. n Davi H. Kim, MD Maureen Spencer, RN Susan M. Davison, MD Ling Li, MSPH Diane Gulczynski, RN Davi J. Hunter, MD, PhD Juli F. Martha, MPH Geral B. Miley, MD Stephen J. Parazin, MD Pamela Dejoie John C. Richmon, MD Department of Orthopaeic Surgery (D.H.K., M.S., D.G., S.J.P., P.D., an J.C.R.); Division of Infectious Disease, Department of Meicine (S.M.D. an G.B.M.); Division of Research (L.L., D.J.H., an J.F.M.); New Englan Baptist Hospital, 125 Parker Hill Avenue, Boston, MA aress for D.H. Kim:hkim@caregroup.harvar.eu Jeremy D. Shaw, BA Case Western Reserve University School of Meicine, Eucli Avenue, Clevelan OH References 1. Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epiemiology, unerlying mechanisms, an associate risks. Clin Microbiol Rev. 1997;10: Melzer M, Eykyn SJ, Gransen WR, Chinn S. Is methicillin-resistant Staphylococcus aureus more virulent than methicillin-susceptible S. aureus? A comparative cohort stuy of British patients with nosocomial infection an bacteremia. Clin Infect Dis. 2003;37: Sexton T, Clarke P, O Neill E, Dillane T, Humphreys H. Environmental reservoirs of methicillin-resistant Staphylococcus aureus in isolation rooms: correlation with patient isolates an implications for hospital hygiene. J Hosp Infect. 2006;62: Boucher HW, Corey GR. Epiemiology of methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2008;46 Suppl 5:S Whitehouse JD, Frieman ND, Kirklan KB, Richarson WJ, Sexton DJ. The impact of surgical-site infections following orthopeic surgery at a community hospital an a university hospital: averse quality of life, excess length of stay, an extra cost. Infect Control Hosp Epiemiol. 2002;23: Perl TM, Golub JE. New approaches to reuce Staphylococcus aureus nosocomial infection rates: treating S. aureus nasal carriage. Ann Pharmacother. 1998;32:S Wenzel RP, Perl TM. The significance of nasal carriage of Staphylococcus aureus an the incience of postoperative woun infection. J Hosp Infect. 1995;31: Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppar D, Twombley J, French PP, Herwalt LA; Mupirocin an the Risk of Staphylococcus Aureus Stuy Team. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Me. 2002;346: Kalmeijer MD, van Nieuwlan-Bollen E, Bogaers-Hofman D, e Baere GA. Nasal carriage of Staphylococcus aureus is a major risk factor for surgical-site infections in orthopeic surgery. Infect Control Hosp Epiemiol. 2000;21: Muñoz P, Hortal J, Giannella M, Barrio JM, Roríguez-Créixems M, Pérez MJ, Rincón C, Bouza E. Nasal carriage of S. aureus increases the risk of surgical site infection after major heart surgery. J Hosp Infect. 2008;68:

8 Morange-Saussier V, Giraueau B, van er Mee N, Lermusiaux P, Quentin R. Nasal carriage of methicillin-resistant staphylococcus aureus in vascular surgery. Ann Vasc Surg. 2006;20: Herwalt LA. Reuction of Staphylococcus aureus nasal carriage an infection in ialysis patients. J Hosp Infect. 1998;40 Suppl B: S Kluytmans JA, Maners MJ, van Bommel E, Verbrugh H. Elimination of nasal carriage of Staphylococcus aureus in hemoialysis patients. Infect Control Hosp Epiemiol. 1996;17: Kluytmans JA, Mouton JW, VanenBergh MF, Maners MJ, Maat AP, Wagenvoort JH, Michel MF, Verbrugh HA. Reuction of surgical-site infections in cariothoracic surgery by elimination of nasal carriage of Staphylococcus aureus. Infect Control Hosp Epiemiol. 1996;17: VanenBergh MF, Kluytmans JA, van Hout BA, Maat AP, Seeren RJ, McDonnel J, Verbrugh HA. Cost-effectiveness of perioperative mupirocin nasal ointment in cariothoracic surgery. Infect Control Hosp Epiemiol. 1996;17: Tacconelli E, Carmeli Y, Aizer A, Ferreira G, Foreman MG, D Agata EM. Mupirocin prophylaxis to prevent Staphylococcus aureus infection in patients unergoing ialysis: a meta-analysis. Clin Infect Dis. 2003;37: Cimochowski GE, Harostock MD, Brown R, Bernari M, Alonzo N, Coyle K. Intranasal mupirocin reuces sternal woun infection after open heart surgery in iabetics an noniabetics. Annals Thorac Surg. 2001;71: Gernaat-van er Sluis AJ, Hoogenboom-Veregaal AM, Eixhoven PJ, Spies-van Rooijen NH. Prophylactic mupirocin coul reuce orthopeic woun infections. 1,044 patients treate with mupirocin compare with 1,260 historical controls. Acta Orthop Scan. 1998;69: National Committee for Clinical Laboratory Stanars (NCCLS). Performance stanars for antimicrobial susceptibility testing. Ninth informational supplement. Document M100-S9. Wayne, PA: National Committee on Clinical Laboratory Stanars; Broerick A, Mori M, Nettleman MD, Stree SA, Wenzel RP. Nosocomial infections: valiation of surveillance an computer moeling to ientify patients at risk. Am J Epiemiol. 1990;131: Trilla A, Nettleman MD, Hollis RJ, Frerickson M, Wenzel RP, Pfaller MA. Restriction enonuclease analysis of plasmi DNA from methicillin-resistant Staphylococcus aureus: clinical application over a three-year perio. Infect Control Hosp Epiemiol. 1993;14: Culver DH, Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG, Banerjee SN, Ewars JR, Tolson JS, Henerson TS, Hughes JM. Surgical woun infection rates by woun class, operative proceure, an patient risk inex. National Nosocomial Infections Surveillance System. Am J Me. 1991;91:152S-7S. 23. Garner JS, Jarvis WR, Emori TG, Horan TC, Hughes JM. CDC efinitions for nosocomial infections, Am J Infect Control. 1988;16: Erratum in: Am J Infect Control. 1988;16: Harbarth S, Fankhauser C, Schrenzel J, Christenson J, Gervaz P, Baniera-Clerc C, Renzi G, Vernaz N, Sax H, Pittet D. Universal screening for methicillin-resistant Staphylococcus aureus at hospital amission an nosocomial infection in surgical patients. JAMA. 2008;299: Rao N, Cannella B, Crossett LS, Yates AJ Jr, McGough R 3r. A preoperative ecolonization protocol for staphylococcus aureus prevents orthopaeic infections. Clin Orthop Relat Res. 2008;466: Kalmeijer MD, Coertjens H, van Nieuwlan-Bollen PM, Bogaers-Hofman D, e Baere GA, Stuurman A, van Belkum A, Kluytmans JA. Surgical site infections in orthopeic surgery: the effect of mupirocin nasal ointment in a ouble-blin, ranomize, placebo-controlle stuy. Clin Infect Dis. 2002;35:353-8.