Ijsa-08-243 180.183

Prevalence of community-associated methicillin-resistantStaphylococcus aureus colonization in men who havesex with men T Antoniou PharmD*†‡, R Devlin MD MHSc*†, K Gough MD MEd*†, M Mulvey PhD§, K C Katz MD MSc**, M Zehtabchi BSc†, J Polsky MSc†, D Tilley MD‡, J Brunetta MD‡, G Arbess MD†, C Guiang MD†, B Chang MD‡, C Kovacs MD‡, A Ghavam-Rassoul MD MHSc†, C Cavacuiti MD MHSc†, B Corneslon MD†, *Leslie Dan Faculty of Pharmacy, University of Toronto; †St Michael’s Hospital, Toronto; ‡Maple Leaf Medical Clinic, Toronto, Ontario;§National Microbiology Laboratory, Winnipeg, Manitoba; **North York General Hospital, Toronto, Ontario, Canada Summary: Outbreaks of skin and soft tissue infections mediated by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are being reported with increasing frequency among men who have sex with men (MSM). However, the potential role of asymptomatic colonization with this organism in perpetuating these infections is unclear. The purpose of this cross-sectional study was to determine the prevalence of colonization with CA-MRSA among a cohort of 500 MSM recruited from two inner city clinics in Toronto, Canada. Following the provision of informed consent, subjects completed a questionnaire capturing demographic and clinical variables, which may be associated with MRSA colonization. A nasal swab for MRSA was collected from each subject, and instructions were provided regarding the self-collection of a rectal swab. Cultured MRSA underwent pulsed-field gel electrophoresis and virulence testing for Panton-Valentine leukocidin gene expression. The prevalence of CA-MRSA colonization Keywords: prevalence, methicillin resistance, Staphylococcus aureus, community-acquired infections, cross-sectional studies protocols. In addition, as most observed infections withCA-MRSA in MSM involve the buttocks or perianal region, the Infections attributable to strains of community-associated possibility of widespread rectal carriage contributing to these methicillin-resistant Staphylococcus aureus (CA-MRSA) are being infections is not understood and requires clarification. The increasingly described among men who have sex with men purpose of this cross-sectional study was to determine the preva- (MSM).1,2 Although much of the published literature thus far lence of CA-MRSA colonization among a large cohort of MSM has focused on MSM who are HIV-positive, recent data followed at two inner city family practice clinics. Outbreaks of confirm that the spread of CA-MRSA among MSM can occur infection with CA-MRSA in MSM had occurred in the year pre- independently of HIV infection and may be sexually transmitted ceding the onset of the study at both clinics, and new infections in this population.3 Risk factors for infection with CA-MRSA were continuing to be observed at both sites at the time of study have been analysed in various studies of HIV-positive MSM, and have included high-risk sexual behaviours, use of crystalmethamphetamine and recent history of sexually transmitteddisease.1,2,4 However, there are few data describing the potential role of asymptomatic colonization in propagating the continuedspread of CA-MRSA among MSM. Such information is import- ant to capture, as the possibility of widespread rectal or nasal Participants were recruited from two study sites in downtown carriage of CA-MRSA among MSM would prompt and inform Toronto between May 2007 and August 2007. Study recruit- the development of relevant prevention and decolonization ment was performed four days per week (Monday –Thursday) during regular clinic hours at both sites. All eligiblepatients who self-identified as MSM and attended either clinic Correspondence to: Dr Tony Antoniou, St Michael’s at these times were informed about the study and invited to Hospital, 410 Sherbourne Street, 4th floor, Toronto, Ontario, participate by means of a study card providing the relevant contact information of the study coordinator. On most occasions, potential participants completed the study the International Journal of STD & AIDS 2009; 20: 180 – 183. DOI: 10.1258/ijsa.2008.008243 Antoniou et al. CA-MRSA colonization in MSM same day of clinic attendance. Ethical approval for the study Fingerprints were compared with those in the national MRSA fingerprint database. A real-time polymerase chain reactionassay was used to detect the presence of the nuc, mecA andPanton-Valentine leukocidin (PVL) genes.9 SCCmec typing Following the provision of informed consent, subjects com-pleted a questionnaire capturing demographic, clinical and behavioural variables that may be associated with MRSA colo-nization. A nasal culture for MRSA was obtained by rotating a Given the extent of the CA-MRSA outbreaks observed at both sterile, moistened rayon swab into both nares, and participants clinics, and colonization rates of 1 –30% reported in studies of were provided with instructions for the on site self-collection of various populations, we estimated a colonization prevalence a rectal swab. Evidence of faecal matter (i.e. yellow or brown of 15% in our cohort.11,12 Screening approximately 200 patients colouration) on rectal swabs was used to confirm proper self- would allow us to determine this proportion with a 95% confi- collection technique. Swabs were placed in liquid Amies dence interval of +5%. To explore the relationship between transport medium and processed within 24 hours of collection.
CA-MRSA colonization and 12 baseline variables, a minimum Isolates that met the Centers for Disease Control (CDC) defi- of 60 patients with positive swabs would be required.13 With nition for community-acquired infection were defined as a prevalence of 15%, a sample size of 500 patients was set to CA-MRSA.5 Specifically, to be classified as CA-MRSA, cultured identify 75 patients colonized with CA-MRSA.
isolates had to be derived from individuals with no history All statistical analyses were performed using SAS version of MRSA infection or colonization, no history of dialysis, 9.1 statistical software (SAS institute, Cary, NC, USA).
surgery, hospitalization or hospice/long-term care facility Comparisons between participants who were colonized and admission in the past year, and no permanent indwelling cath- were not colonized with CA-MRSA were made using the eters or percutaneous devices. Although the questionnaire was appropriate bivariate non-parametric tests (Fisher’s Exact and designed to capture these variables, participants from whom a median tests for categorical and continuous variables, positive nasal or rectal culture for MRSA was obtained were interviewed to ensure that the CDC criteria for being acommunity-associated strain were met, and the patient chartwas reviewed to clarify vague or ambiguous information.
A total of 500 subjects were enrolled in the study, of whom298 (59.6%) were HIV-positive. Demographic characteristics of Laboratory identification and antimicrobial the cohort are summarized in Table 1. The median age of the entire cohort was 43 years (interquartile range [IQR] 37, 49).
Clinical specimens were inoculated onto an MRSA Selectw Seventy-one (14.2%) participants had received antibiotic therapy (Bio-Rad, Hercule, CA, USA) plate, streaked for isolation of within three months preceding the study. The median viral load single colonies and incubated at 358C aerobically for 24 – and CD4þ cell count of the HIV-positive participants were 48 hours. Pink colonies were confirmed as Staphylococcus 1.69 log10copies/mL (IQR 1.69, 2.83) and 420 cells/mm3 (IQR aureus by testing for coagulase production. Screening for methi- 280, 650), respectively. A total of 181 (60.7%) HIV-positive partici- cillin resistance was conducted using a Mueller-Hinton agar pants had a viral load of ,50 copies/mL, and 36 (12.1%) were plate with 4% sodium chloride and 6 mg/mL of oxacillin, incu- receiving daily TMP-SMX for Pneumocystis jirovecii disease bated at 358C for 24 hours. Oxacillin-resistant Staphylococcus aureus isolates were confirmed as MRSA using the Vitek Of the 500 screened patients, 8 (1.6% [95% CI: 0.6–2.6%]) had system (BioMerieux Inc., Hazelwood) and by testing for the MRSA cultured from either the rectum (n ¼ 2), the nares (n ¼ 3) production of penicillin-binding protein 2a (Denka Sieken Co, or both sites (n ¼ 3). All isolates met the predefined criteria for being community-associated. Four of the eight patients from Susceptibility to clindamycin, erythromycin, rifampin, van- whom CA-MRSA was cultured were HIV-positive. The median number of sexual partners in the three months preceding the study was significantly higher among participants colonized Erythromycin-inducible clindamycin resistance was assessed with CA-MRSA relative to those who were not (7 [IQR 5, 12] vs.
with a double-disk diffusion test (D-test).6 Minimum inhibitory 2 [IQR 1, 4]; P ¼ 0.0091). There were no significant differences concentrations (MICs) to fusidic acid and mupirocin were observed between the groups with respect to other variables determined using the E-test system (AB Biodisk, Solna) and examined, including recent (i.e. within three months) treatment interpreted in accordance with the Clinical and Laboratory for a sexually transmitted disease (P ¼ 0.09), antibiotic use (P ¼ Standards Institute breakpoint criteria.7 0.09) and engagement in high-risk sexual behaviours (P ¼ 0.15).
Isolates were uniformly sensitive to vancomycin, rifampin, TMP-SMX was observed in one HIV-positive participant despite a lack of recent exposure to this agent. Clindamycin and erythro- Cultured isolates were subtyped using pulsed-field gel electro- mycin resistance were observed in two and 10 of the 11 isolates, phoresis (PFGE) as previously described.8 PFGE-generated fingerprints were digitized and analysed with BioNumerics Based on PFGE patterns, nine of the 11 isolates were identified Version 3.5 (Applied Maths, Sint-Martens-Latem, Belgium) as strains of USA300 (CMRSA-10), and a further isolate was ident- using a position tolerance of 1.0 and optimization of 1.0.
ified as USA400 (CMRSA-7). The remaining isolate had a PFGE Our study adds to the existing small body of literature exam- ining CA-MRSA colonization in MSM. In the only other study looking at a cohort comprised exclusively of MSM, seven of 158 participants had a nasal culture that was positive for CA-MRSA.14 Rectal carriage was not assessed by these investi- gators. Given that five of 11 isolates of CA-MRSA in our study were cultured from rectal swabs, future studies addressing the question of CA-MRSA prevalence among MSM should include collection and culture of rectal swabs, as the sole reliance on Health-care associated risk factors in previous year nasal swabs may underestimate the prevalence of colonization in this population. In a separate study performed at an urban Hospice and/or shelter (overnight or longer) outpatient clinic, 15 of 279 (5.4%) patients had MRSA cultured from the nares, 13 of whom were MSM. However, although the majority of patients enrolled in the study were MSM, this was Treated for skin infection in past 3 months not a study performed exclusively in this population. In Number of sexual partners in past 3 monthsà addition, it is unclear what criteria were in place to ascertain whether strains were community-derived or health-care associ- ated.15 Finally, an additional published study examined the prevalence of nasal MRSA colonization in 162 HIV-positive outpatients, 144 of whom were men.16 A colonization rate of 6% was observed in this cohort, although it is unclear if these Treated for sexually transmitted disease (other than HIV) isolates met the definition for being community-derived, and Our study has several strengths, including the large sample of participants enrolled from two community clinics, use of predefined criteria for determining whether isolates were community-associated, molecular typing of strains and assess- Within past 3 months, had close contact with someone who ment of both nasal and rectal carriage. However, there are several limitations to our study. As both clinics had experienced outbreaks of CA-MRSA infections among MSM in the year preceding the initiation of this study, infection control Had been treated for skin infection with antibiotics measures and educational initiatives directed towards the com- ARVs ¼ antiretrovirals; TMP-SMX ¼ trimethoprim-sulfamethoxazole; MRSA ¼ munity may have resulted in a decreased rate of colonization methicillin-resistant Staphylococcus aureus relative to a period preceding the identification of CA-MRSA as a significant public health concern among this cohort.
In addition, we were statistically limited in our ability toperform any multivariable regression analysis to assess the fingerprint pattern that was not described in the national MRSA role of healthcare-associated or demographic variables as risk database. Ten of the 11 isolates were PVL-positive, and all were factors for CA-MRSA colonization, given the small number of found to carry the SCCmec type IVa gene.
patients with a positive culture. Similarly, the finding ofsignificantly more sexual contacts among participants whowere colonized may be spurious given the small number of out-comes observed and large number of comparisons drawn.
Still, this finding cannot be dismissed entirely, given prior The prevalence of CA-MRSA nasal or rectal carriage in our evidence identifying sex with multiple partners as a risk cohort of MSM was 1.6%, implying that colonization with factor for CA-MRSA skin infections in MSM. In addition, the this organism has not occurred in this population to a signifi- possibility of non-response bias cannot be excluded as refusal cant extent. These findings are similar to those attained in sur- rates and reasons for refusal were not recorded in the study.
veillance studies of other community dwelling populations and Finally, it is possible that self-collection of rectal swabs may are mirrored by the pooled CA-MRSA colonization prevalence have affected the results, although patients were instructed on of 1.3% attained by meta-analysis of studies conducted among the proper collection technique and a study coordinator was healthy community members.11,12 Widespread colonization available if problems with this procedure arose. No participant with CA-MRSA is therefore unlikely contributing to the was required to repeat the rectal swab due to incorrect speci- ongoing nature of the outbreaks of purulent skin and soft tissue infections being observed in the MSM population in In summary, we observed a low prevalence of colonization the clinic catchment area. It is therefore more likely that new with CA-MRSA among a large cohort of MSM seen at two infections with CA-MRSA in our MSM clients are occurring inner city family practice clinics. These data suggest that new secondary to direct skin-to-skin contact with an infected infections are not occurring as a result of widespread asympto- person or by indirect transmission mediated by contaminated matic nasal or rectal colonization in this community.
clothing, equipment or other fomites. The colonizing strains In addition, our data do not support routine screening of observed in our cohort were consistent with those most MSM for asymptomatic carriage of CA-MRSA. Instead, strat- egies aimed at disrupting the continual spread of this organism within the MSM community would likely be most successful if Antoniou et al. CA-MRSA colonization in MSM emphasis was placed on basic infection control measures in Centers for Disease Control and Prevention. See: www.cdc.gov/ncidod/ venues such as bath-houses, gyms or other centres where dhqp/ar_mrsa_ca_clinicians.html (last checked 27 March 2008) 6 Feibelkorn KR, Crawfors SA, McElmeel ML, Jorgensen JH. Practical disc contact with potentially contaminated surfaces can occur.
diffusion method for detection of inducible clindamycin resistance inStaphylococcus aureus and coagulase-negative staphylococci. J Clin Microbiol2003;41:4740–4 7 Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Sixteenth Informational Supplement This study was funded by the AIDS Bureau, Ministry of Health and Long Term Care, Ontario. We would like to thank Ms 8 Mulvey MR, Chui L, Ismail J, et al. Development of a Canadian standardized Wendy Small (SMH) and the staff of the St Michael’s protocol for subtyping methicillin-resistant Staphylococcus aureus usingpulsed-field gel electrophoresis. J Clin Microbiol 2001;39:3481 –5 Hospital Microbiology Laboratory for their technical assistance 9 McDonald RR, Antonishyn NA, Hansen T, et al. Development of a triplex with this study, Ms Tatjana Reko (MLM) and Ms Roberta real-time PCR assay for detection of Panton-Valentine leukocidin toxin genes Halpenny (MLM) for their assistance in coordinating the in clinical isolates of methicillin-resistant Staphylococcus aureus. J Clin Microbiol study. We would also like to thank Ms Jennifer Campbell 10 Oliveira DC, de Lencastre H. Multiplex PCR strategy for rapid (NML) and Mr Dave Spreitzer (NML) for molecular typing identification of structural types and variants of the mec element in analysis and Ms Melissa McCracken (NML) for PCR confir- methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother mation of MRSA and PVL toxin determination.
Funding: Funded by the AIDS Bureau, Ontario Ministry of 11 Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin InfectDis 2003;36:131 –9 12 Kuehnert MJ, Kruszon-Moran D, Hill HA, et al. Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001 –2002. J Infect Dis 13 Kleibaum DG, Kupper LL, Muller KE. Applied Regression Analysis and Other 1 Crum-Cianflone NF, Burgi AA, Hale BR. Increasing rates of Multivariable Methods. 2nd ed. Boston, MA: PWS-Kent Publishing Company, community-acquired methicillin-resistant Staphylococcus aureus infections among HIV-infected persons. Int J STD AIDS 2007;18:521 –6 14 Rieg G, Daar E, Witt M, Guerrero M, Miller L. Community-acquired 2 Lee NE, Taylor MM, Bancroft E, et al. Risk factors for community-associated methicillin resistant Staphylococcus aureus colonization among HIV-infected methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men: a point prevalence survey [abstract 877].
men who have sex with men. Clin Infect Dis 2005;40:1529 –34 2005; Presented at the 12th Conference on Retroviruses and Opportunistic Infections, 3 Diep BA, Chambers HF, Graber CJ, et al. Emergence of multidrug-resistant, community-associated, methicillin-resistant Staphylococcus aureus clone 15 Wener KM, Gold HS, Wong M, et al. High prevalence of methicillin-resistant USA300 in men who have sex with men. Ann Intern Med 2008;148:249 –57 Staphylococcus aureus (MRSA) colonization in an urban outpatient population 4 Ly LT, Revuelta MP, Hongo I, Kreisworth BN, Davis S, Saltzman BR. Clonal [abstract 380]. 2006; Presented at the 44th Annual Meeting of the Infectious outbreak of community-acquired methicillin-resistant Staphylococcus aureus Diseases Society of America, Toronto, 12 –15 October skin abscesses in men who have sex with men in New York City: possible 16 McDonald LC, Lauderdale TL, Lo HJ, Tsai JJ, Hung CC. Colonization association with crystal methamphetamine usage (abstract 490). 2004; of HIV-infected outpatients in Taiwan with methicillin-resistant and Presented at the 42nd Annual Meeting of the Infectious Diseases Society of America, methicillin-susceptible Staphylococcus aureus. Int J STD AIDS 2003;14:473 –7 5 Department of Health and Human Services, Centers for Disease Control and Prevention. Community-associated MRSA Information for Clinicians. Atlanta, GA:

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