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Emergence of Multidrug-Resistant, Community-Associated, Methicillin-Resistant Staphylococcus aureus Clone USA300 in Men Who Have Sex with Men FREE

Binh An Diep, PhD; Henry F. Chambers, MD; Christopher J. Graber, MD, MPH; John D. Szumowski, MD, MPH; Loren G. Miller, MD, MPH; Linda L. Han, MD; Jason H. Chen, BA; Felice Lin, BA; Jessica Lin, BA; Tiffany HaiVan Phan, BA; Heather A. Carleton, MPH; Linda K. McDougal, MS; Fred C. Tenover, PhD; Daniel E. Cohen, MD; Kenneth H. Mayer, MD; George F. Sensabaugh, DCrim; and Françoise Perdreau-Remington, PhD
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From the University of California, San Francisco, San Francisco, Harbor-University of California, Los Angeles, Medical Center, Torrance, and University of California, Berkeley, Berkeley, California; Beth Israel Deaconess Medical Center, Massachusetts Department of Public Health, and The Fenway Institute of Fenway Community Health, Boston, Massachussetts; Centers for Disease Control and Prevention, Atlanta, Georgia; and Brown University and Miriam Hospital, Providence, Rhode Island.


Acknowledgment: The authors thank Dr. David A. Talan for providing isolates and clinical data.

Grant Support: By U.S. Public Health Service grant R01/CCR923381 (Dr. Chambers); University of California, Berkeley, Faculty Research Grant (Dr. Sensabaugh); unrestricted grant from Pfizer (Dr. Perdreau-Remington); Microbial Pathogenesis and Host Defense Postdoctoral Fellowship (5T32AI060537-02) (Dr. Diep) and HIV Translational Research Fellowship (5T32AI060530-02) (Dr. Graber) from the University of California, San Francisco; and U.S. Public Health Service grant R01/CCR923419 (Dr. Miller).

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement: Study protocol, statistical code, and portions of deidentified data are available from Dr. Diep (e-mail, bdiep@epi-center.ucsf.edu).

Requests for Single Reprints: Binh An Diep, PhD, Department of Medicine, University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Building 30, Room 3300, San Francisco, CA 94110; e-mail, bdiep@epi-center.ucsf.edu.

Current Author Addresses: Drs. Diep, Chambers, Graber, and Perdreau-Remington; Ms. Phan; and Ms. Carleton: University of California, San Francisco, San Francisco General Hospital, 1001 Potrero Avenue, Building 30, Room 3300, San Francisco, CA 94110.

Dr. Szumowski: Beth Israel Deaconess Medical Center, Deaconess 311, 330 Brookline Avenue, Boston, MA 02215.

Dr. Miller: Harbor-UCLA Medical Center, 1000 West Carson Street, Box 466, Torrance, CA 90509.

Dr. Han: State Laboratory Institute, 305 South Street, Jamaica Plain, MA 02130.

Mr. Chen, Ms. F. Lin, Ms. J. Lin, and Dr. Sensabaugh: School of Public Health, MC#7360, University of California, Berkeley, CA 94720.

Ms. McDougal and Dr. Tenover: Centers for Disease Control and Prevention, 1600 Clifton Road, Atlanta, GA 30333.

Dr. Cohen: Fenway Community Health, 7 Haviland Street, Boston, MA 02115.

Dr. Mayer: Brown University/Miriam Hospital, 164 Summit Avenue, Providence, RI 02906.

Author Contributions: Conception and design: B.A. Diep, C.J. Graber.

Analysis and interpretation of the data: B.A. Diep, C.J. Graber, J.D. Szumowski, L.G. Miller, L.L. Han, F.C. Tenover, D.E. Cohen, K.H. Mayer, G.F. Sensabaugh, F. Perdreau-Remington, H.F. Chambers.

Drafting of the article: B.A. Diep.

Critical revision of the article for important intellectual content: B.A. Diep, C.J. Graber, H.F. Chambers, G.F. Sensabaugh, F. Perdreau-Remington, J.D. Szumowski, L.G. Miller, L.L. Han, J.H. Chen, F. Lin, J. Lin, T.H. Phan, H.A. Carleton, L.K. McDougal, F.C. Tenover, D.E. Cohen, K.H. Mayer.

Final approval of the article: B.A. Diep, H.F. Chambers, C.J. Graber, J.D. Szumowski, L.G. Miller, L.L. Han, J.H. Chen, F. Lin, J. Lin, T.H. Phan, H.A. Carleton, L.K. McDougal, F.C. Tenover, D.E. Cohen, K.H. Mayer, G.F. Sensabaugh, F. Perdreau-Remington.

Provision of study materials or patients: H.F. Chambers, F. Perdreau-Remington, L.G. Miller, L.L. Han, D.E. Cohen, K.H. Mayer.

Statistical expertise: B.A. Diep, C.J. Graber, L.G. Miller.

Obtaining of funding: H.F. Chambers, G.F. Sensabaugh, F. Perdreau-Remington.

Collection and assembly of data: B.A. Diep, C.J. Graber, J.D. Szumowski, J.H. Chen, F. Lin, J. Lin, T.H. Phan, H.A. Carleton, L.K. McDougal, L.L. Han.


Ann Intern Med. 2008;148(4):249-257. doi:10.7326/0003-4819-148-4-200802190-00204
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Editors' Notes
Context

  • Researchers have recently identified multidrug-resistant USA300, a clone of community-acquired, methicillin-resistant Staphylococcus aureus (MRSA) that is resistant to multiple antibiotics.

Contribution

  • The authors demonstrate that the incidence of multidrug-resistant USA300 MRSA is highest in the areas of San Francisco where more male same-sex couples reside. The infection frequently manifests as an abscess or cellulitis in the buttocks, genitals, or perineum, and male–male sex was a risk factor.

Caution

  • Data were passively reported or retrospectively collected and are therefore subject to bias.

Implication

  • Multidrug-resistant USA300 MRSA infection is especially common among men who have sex with men. It might be sexually transmitted in this population.

—The Editors

Infections caused by community-associated, methicillin-resistant Staphylococcus aureus (MRSA) have become a major public health threat. A single clone of community-associated MRSA, USA300, was not seen before 2000 but is now widely disseminated in 38 U.S. states, Canada, and 9 European Union countries (117). It can cause unusually severe disease, including necrotizing fasciitis, sepsis, endocarditis, and pneumonia (1823). Infections occur predominantly among healthy, community-dwelling persons who lack traditional risk factors for MRSA (9, 18, 2426).

Whereas hospital-associated MRSA strains are resistant to multiple antimicrobial classes, USA300 and other community-associated MRSA strains are typically resistant to β-lactams and 1 or 2 other drug classes. Older generic antimicrobials, such as clindamycin, tetracycline, or trimethoprim–sulfamethoxazole, are recommended for treating less serious community-associated MRSA infections, such as uncomplicated skin and soft tissue infections (3, 27). However, increased use of these antimicrobials could drive the emergence of new subclones of community-associated MRSA that are multidrug resistant. Recently, Diep and colleagues (28) described a multidrug-resistant USA300 isolate that had accumulated multiple resistance genes, rendering it resistant to β-lactams, fluoroquinolones, tetracycline, macrolide, clindamycin, and mupirocin. Two of the resistance genes from this isolate, ermC and mupA—which determine constitutive resistance to macrolides, clindamycin, and mupirocin—are carried on a large conjugative plasmid called pUSA03 (28). Researchers have identified clusters of infections due to multidrug-resistant USA300 in San Francisco and Boston (2930), which could complicate disease management and contribute to development of persistent or recurrent community-associated MRSA infections (3132).

We report the incidence of multidrug-resistant USA300 in San Francisco and Boston among men who have sex with men, and we describe factors associated with its spread in this high-risk population, on the basis of 4 studies: a population-based survey to estimate the incidence and spatial clustering of multidrug-resistant USA300 in San Francisco; 2 clinic-based, cross-sectional studies to identify risk factors for multidrug-resistant USA300 infection; and a post hoc analysis of multidrug-resistant USA300 isolates previously collected from emergency departments (1).

Population-Based Survey

We characterized MRSA isolates previously collected in a population-based survey of MRSA infections at 9 of the 10 medical centers serving San Francisco in 2004 to 2005 (Liu C, Graber CJ, Karr M, Diep BA, Basuino L, Schwartz BS, et al. A population-based study of the incidence and molecular epidemiology of methicillin-resistant-Staphylococcus aureus disease in San Francisco, 2004-5. In preparation). The medical centers used passive surveillance for MRSA; physicians submitted cultures to laboratories for identification of pathogens when patients presented with a disease that, in the physician's opinion, required culture. The 9 medical centers operate 4368 licensed hospital beds; the medical center that did not participate in the survey operates 59 licensed hospital beds. The participating medical centers initiated routine specimen collection between February and September 2004 and collected clinical MRSA specimens from unique patients (n = 3929) for 12 consecutive months. If a specimen was submitted from a patient for whom a sample was cultured earlier in the study period, we used the first specimen. We excluded 103 isolates because they came from patient nares and did not represent active infection. Of the remaining 3826 MRSA specimens, 2495 were from patients residing in San Francisco. The 3826 MRSA specimens were stratified by the medical center of origin and then by the month of specimen collection, and we used a random-number generator to select up to 8 MRSA specimens from each stratum. The stratified random sample comprised 801 nonduplicated MRSA specimens, and of these, 532 were recovered from patients residing in San Francisco. We calculated the incidence of multidrug-resistant USA300 infection in each city ZIP code on the basis of the 532 cases, and we used 2000 U.S. Census data (33) to test the association between disease incidence estimates and the proportion of male same-sex couples living in those ZIP codes.

HIV Clinic–Based Study

We conducted a retrospective chart review of consecutive patients (n = 183) who had MRSA cultured from an infection site from January 2004 through June 2006 at the San Francisco General Hospital (SFGH) Positive Health Program, an outpatient HIV clinic that provides specialized HIV and AIDS care in San Francisco, California. Of the 183 specimens, 83 were collected between 1 February 2004 and 31 January 2005 as part of the population-based survey; these 83 specimens represented a subset of 1014 unique MRSA isolates identified from all SFGH sites in the population survey. Using a standardized instrument, we abstracted information about patients' demographic characteristics, male homosexual behavior, HIV viral load, CD4+ cell count, past culture-proven MRSA infection, past clinical presentation, and site of infection from medical records. We collected information about male homosexual behavior from the patient's clinic intake form (typically administered by a social worker), in which the patient was asked for self-identification of sexual behavior. If the clinic intake form was incomplete or missing, we classified a male patient as a man who has sex with men if an anal Papanicolaou (Pap) smear was performed at any time during his history at the clinic in the absence of indications other than anal receptive intercourse (screening anal Pap smear). Eight patients had missing sexual behavior data and no history of anal Pap smears; we classified them as men who do not have sex with men. Seven of these men had non–multidrug-resistant USA300 infection, and 1 had a non-USA300 infection. Our estimates of risk for multidrug-resistant USA300 with male–male sex did not change meaningfully when these 7 patients with non–multidrug-resistant USA300 infection were reclassified as occurring in men who have sex with men or when they were excluded from analyses (data not shown).

We also compared the proportion of patients with multidrug-resistant USA300 infection in the HIV clinic with a subset of 91 MRSA cases randomly selected from the 1014 MRSA isolates identified from SFGH in the population-based study.

Community Health Clinic–Based Study

We conducted retrospective chart reviews of 130 consecutive patients with MRSA infection treated at Fenway Community Health, Boston, Massachusetts, from April 2004 through March 2006. Fenway Community Health is a community-based organization that provides primary care to more than 10 000 patients annually (34). Reports have noted that a large proportion of MRSA isolates recovered from skin and soft tissue infection sites of patients seen at Fenway Community Health were resistant to multiple antimicrobial agents (30, 31). Using the same standardized instrument developed for the SFGH HIV clinic study, we abstracted clinical data from medical records of each patient at Fenway Community Health.

Among these patients, 3 with missing data on sexual behavior and no history of screening anal Pap smears were classified as men who do not have sex with men; these 3 patients had non–multidrug-resistant USA300 infections. We genotyped the multidrug-resistant USA300 isolate of 1 clinic patient who reported male–male sex and frequent travel to and from the Castro District in San Francisco to see whether frequent travel by men who have sex with men between the East and West coasts facilitates the clonal spread of multidrug-resistant USA300.

Emergency Department–Based Study

Because the spread of multidrug-resistant USA300 is a potential public health threat, we investigated the distribution of multidrug-resistant USA300 in the general population of patients with community-associated MRSA infections. To this end, we conducted a post hoc analysis of 212 USA300 isolates collected by Moran and colleagues (1) in August 2004 from emergency departments in 11 U.S. cities.

The study was approved by the University of California, San Francisco, Committee on Human Research and the institutional review board of Fenway Community Health; the institutions waived the informed consent process because the study involved retrospective chart reviews.

Antimicrobial Susceptibility Testing

We tested isolates for susceptibility to oxacillin, ciprofloxacin, erythromycin, tetracycline, clindamycin, trimethoprim–sulfamethoxazole, gentamicin, vancomycin, linezolid, and mupirocin and interpreted the results in accordance with the Clinical and Laboratory Standards Institute guidelines (35). We performed inducible clindamycin resistance (D-zone test) by using the agar disk diffusion method in accordance with Clinical and Laboratory Standards Institute guidelines (35).

Molecular Analysis

We genotyped isolates by using pulsed-field gel electrophoresis after SmaI-macrorestriction digest of chromosomal DNA (36), spa typing of the polymorphic repeat regions of protein A (37), and multilocus sequence typing of fragments of 7 housekeeping genes (38). We further defined USA300 by the presence of Panton–Valentine leukocidin genes (lukF-PV and lukS-PV) and the arginine catabolic mobile element by using polymerase chain reaction assays (28). We defined multidrug-resistant USA300 by its carriage of the multiresistance conjugative plasmid pUSA03, which was assessed by using polymerase chain reaction assays and whole plasmid DNA sequencing, as described in the Appendix.

Statistical Analysis

We analyzed the population-based survey data by weighting each of the 532 cases originating from patients residing San Francisco by the inverse of the probability of being included in the sample, so that the results reflect estimates for the entire population of San Francisco (39). On the basis of each patient's ZIP code of residence, we estimated the number of new cases for each San Francisco ZIP code by using the Stata subroutine svytab, which accounted for the stratified random sampling design (Stata, version 9, College Station, Texas). By using ZIP code–derived population estimates from the 2000 U.S. Census (Summary File 3 [33]), we calculated the annual incidence rates for San Francisco as a whole and for each of its 26 ZIP codes. We used Epimap (version 3.2.2, Centers for Disease Control and Prevention, Atlanta, Georgia) to display the distribution of the ZIP code–specific incidence rates, with boundary files obtained from the Family Health Outcomes Project (40). In the 2 cross-sectional studies, we used 2-sided chi-square or Fisher exact tests to evaluate associations between multidrug-resistant USA300 infections and demographic or clinical characteristics, and we used the Cochran–Mantel–Haenszel procedure to calculate unadjusted and adjusted relative risks for multidrug-resistant USA300 infection with associated 95% CIs (Stata, version 9).

Role of the Funding Source

Centers for Disease Control and Prevention; University of California, Berkeley and San Francisco; and Pfizer funded this study. The funding sources had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Population-Based Survey

On the basis of a stratified random sample of 532 (21%) of 2495 San Francisco residents who had a culture-proven MRSA infection that was treated at 9 of 10 medical centers serving San Francisco, we estimated the annual incidence of USA300 infection in San Francisco to be 275 cases per 100 000 persons (CI, 256 to 295 cases per 100 000 persons). The annual incidence of multidrug-resistant USA300 infection containing multiresistance conjugative plasmid pUSA03 was 26 cases per 100 000 persons (CI, 16 to 36 cases per 100 000 persons). Eight contiguous San Francisco ZIP codes had an average incidence of multidrug-resistant USA300 of 59 cases per 100 000 persons (CI, 36 to 82 cases per 100 000 persons) (Figure), compared with 4 cases per 100 000 persons (CI, 0 to 8 cases per 100 000 persons) for the other 18 ZIP codes (relative risk, 16.1 [CI, 9.8 to 26.5]). According to 2000 U.S. Census data (33), 10.3% (4896 of 47 664) of couples in the 8 ZIP codes with high incidence of multidrug-resistant USA300 were male same-sex couples, compared with 2.2% (1771 of 81 141) in the other 18 ZIP codes (P < 0.001). The Castro District (ZIP code 94114), which had the highest percentage (25.7%) of male same-sex couples of any ZIP code in the United States, had an incidence of multidrug-resistant USA300 of 170 cases per 100 000 persons (CI, 41 to 299 cases per 100 000 persons) (Figure). Taken together, the data suggest that men who have sex with men may be at increased risk for infection with multidrug-resistant USA300.

Grahic Jump Location
Figure.
Annual incidence of multidrug-resistant USA300 infection and percentage of male same-sex couples, by San Francisco ZIP code.

The key indicates the annual incidence of multidrug-resistant USA300 infection per 100 000 persons. The number within each ZIP code is the percentage of male same-sex couples, calculated by dividing the number of male same-sex, unmarried-partner households by the number of coupled (married and unmarried) households for each ZIP code, based on 2000 U.S. Census (Summary File 3) data (33). *Location of the San Francisco General Hospital HIV clinic.

Grahic Jump Location
HIV Clinic–Based Study

The SFGH HIV clinic is located in a ZIP code with high prevalence of multidrug-resistant USA300 (Figure). The 183 consecutive patients with MRSA infection treated at the SFGH HIV clinic were predominantly male (85%), white (54%), and men who have sex with men (69%) and had a median age of 40 years (interquartile range, 34 to 47 years). Most (n = 179) had skin and soft tissue infections that manifested as an abscess (n = 121), cellulitis (n = 17), folliculitis (n = 18), impetigo (n = 2), ulceration (n = 6), and wound infection (n = 15). The remaining 4 patients had non–multidrug-resistant USA300 or non-USA300 infection that manifested as joint infection, acute sinusitis, bloodstream infection, and pneumonia. Forty-five (25%) patients had infections involving the buttocks, genitals, or perineum (buttocks [n = 27], scrotum [n = 6], penis [n = 5], perianal area [n = 3], pubic region [n = 2], rectum [n = 1], and vulva [n = 1]).

Of the 183 MRSA cases, 170 (93%) were USA300 and 13 (7%) were non-USA300. Of the 170 USA300 cases, 30 were multidrug-resistant USA300 (16% of all MRSA cases) and 140 were non–multidrug-resistant USA300 (76% of all cases) (Table 1). In comparison, multidrug-resistant USA300 accounted for only 2 of 91 (2%) MRSA cases randomly selected from the 1014 MRSA isolates identified from throughout SFGH in the population-based study (P < 0.001). Among the 118 men who have sex with men, the proportion of USA300 and multidrug-resistant USA300 infections that involved the buttocks, genitals, or perineum was 27% (32 persons) and 11% (13 persons), respectively.

Table Jump PlaceholderTable 1.  Distribution of Methicillin-Resistant Staphylococcus aureus Genotypes and Antimicrobial Resistance Profiles at the San Francisco General Hospital HIV Clinic

In bivariate analyses, having male–male sex increased the risk for multidrug-resistant USA300 infection (relative risk, 12.8 [CI, 1.8 to 91.3]) (Table 2). Twenty-nine of the 30 patients with multidrug-resistant USA300 infection had a history of having male–male sex, consistent with the high incidence of multidrug-resistant USA300 observed in San Francisco ZIP codes with high percentages of male same-sex couples (Figure). The proportion of multidrug-resistant USA300 infections that involved the buttocks, genitals, or perineum was 30% (13 of 43 persons), whereas the proportion of multidrug-resistant USA300 infections that involved other sites was 14% (17 of 121 persons) (relative risk, 2.2 [CI, 1.1 to 4.1]). Other risk factors for infection with multidrug-resistant USA300 were past MRSA infection (relative risk, 3.2 [CI, 1.7 to 5.9]) and past use of clindamycin (relative risk, 2.8 [CI, 1.5 to 5.3]) and trimethoprim–sulfamethoxazole (relative risk, 2.2 [CI, 1.1 to 4.2]). In a multivariable analysis simultaneously adjusted for the 3 strongest predictors of developing multidrug-resistant USA300 infection, namely male–male sex, past MRSA infection, and past use of clindamycin, all 3 risk factors retained their strong association with multidrug-resistant USA300 infection (Table 3).

Table Jump PlaceholderTable 2.  Risk Factors for Multidrug-Resistant USA300 Infections among Outpatients in San Francisco and Boston*
Table Jump PlaceholderTable 3.  Adjusted Relative Risk for Multidrug-Resistant USA300 Infections among Outpatients Treated at the San Francisco General Hospital HIV Clinic*
Community Health Clinic–Based Study

Of 130 patients with MRSA infection, 126 (97%) were infected with USA300 and 4 (3%) were infected with non-USA300; of the 126 USA300 infections, 60 were multidrug-resistant USA300 (46% of all MRSA cases) and 66 were non–multidrug-resistant USA300 (51% of all cases). Compared with the 170 patients with USA300 infection from the SFGH HIV clinic (Table 2), the 126 patients with USA300 infection from Fenway Community Health were more likely to be white (86% vs. 56%; P < 0.001); have male–male sex (96% vs. 69%; P < 0.001); and have infections involving the buttocks, genitals, or perineum (37% vs. 25%; P = 0.026). They were also less likely to have HIV infection (45% vs. 100%; P < 0.001) or to have used clindamycin in the preceding 12 months (1% vs. 20%; P < 0.001). The 1 Fenway Community Health patient who had used clindamycin in the preceding 12 months had multidrug-resistant USA300 infection. Among the 121 men who have sex with men in the Fenway Community Health sample, the proportions of those with USA300 and multidrug-resistant USA300 infections that involved the buttocks, genitals, or perineum were 39% (47 patients) and 18% (22 patients), respectively.

As in the SFGH HIV clinic population, having male–male sex was a risk factor for multidrug-resistant USA300 infection among patients in the Fenway Community Health sample (Table 2). All patients in this sample who had multidrug-resistant USA300 infection were men who had sex with men, and none of the more than 3000 men seen at this health center annually who did not have male–male sex had multidrug-resistant USA300 infection, suggesting the exclusive spread of the multidrug-resistant USA300 clone among men who have sex with men. Infection with HIV seemed to be a risk factor (Table 2). In a subgroup analysis involving only the 121 USA300-infected men who have sex with men, 33 of 56 (59%) who were HIV positive had multidrug-resistant USA300 infection compared with 27 of 65 (42%) who were HIV negative (relative risk, 1.4 [CI, 1.0 to 2.0]; P = 0.056). We could not calculate the adjusted relative risk for multidrug-resistant USA300 infection for men who have sex with men after controlling for the potential confounding effects of HIV infection because the 5 patients who did not have male–male sex also did not have multidrug-resistant USA300 infection. Nonetheless, these data suggest that although HIV infection is a risk factor for multidrug-resistant USA300 infection, having male–male sex is also a risk factor independent of HIV infection.

We noted a multidrug-resistant USA300 isolate from 1 patient treated at Fenway Community Health for multidrug-resistant USA300 infection who reported having male–male sex and a history of frequent travel to and from the Castro District, the epicenter of multidrug-resistant USA300 infection in San Francisco (Figure). The isolate has the pulsed-field gel electrophoresis subtype USA300-0114, as does the vast majority of multidrug-resistant USA300 isolates in San Francisco (28). The isolate also contained a 37136–base pair plasmid identical in nucleotide sequence to the multiresistance pUSA03 found in multidrug-resistant USA300 isolates from San Francisco (Appendix) (28), indicating that men who have sex with men and frequently travel between Boston and San Francisco may facilitate the clonal spread of multidrug-resistant USA300.

Emergency Department–Based Study

In our post hoc analysis of 212 USA300 isolates collected in August 2004 from emergency departments in 11 U.S. cities (1), 8 isolates were constitutively resistant to clindamycin. We tested these 8 clindamycin-resistant USA300 isolates and found that only 2 carried the multidrug-resistant plasmid pUSA03. One of these isolates was recovered from an 81-year-old woman from New York City, and 1 was recovered from a 37-year-old man from Los Angeles who was identified as a man who has sex with men (Talan D. Personal communication.). These findings suggest that multidrug-resistant USA300 is presently rare in the general population.

Multidrug-resistant USA300 is the first widely disseminated, community-associated, multidrug-resistant MRSA clone. Emergence of multidrug-resistant USA300 in the community suggests that the USA300 lineage can overcome the presumed fitness cost of multidrug resistance. Data from this study suggest that multidrug-resistant USA300 has spread rapidly among men who have sex with men in San Francisco and Boston and that having male–male sex seems to be a risk factor for multidrug-resistant USA300 infection independent of HIV infection. Although the use of clindamycin and mupirocin, 2 antimicrobial agents that can select for multidrug-resistant USA300 over non–multidrug-resistant USA300 strains, may have contributed to the spread of multidrug-resistant USA300 in men who have sex with men in San Francisco (Tables 1, 2, and 3), the data also suggest that antimicrobial use is not an a priori condition for the spread of multidrug-resistant USA300 given the infrequent use of clindamycin and mupirocin among the Fenway Community Health sample.

Spread of the USA300 clone among men who have sex with men is associated with high-risk behaviors, including use of methamphetamine and other illicit drugs, sex with multiple partners, participation in a group sex party, use of the Internet for sexual contacts, skin-abrading sex, and history of sexually transmitted infections (4143). The same patterns of increased sexual risk behaviors among men who have sex with men—which have resulted from changes in beliefs regarding HIV disease severity with the availability of potent antiretroviral therapy—have been driving resurgent epidemics of early syphilis, rectal gonorrhea, and new HIV infections in San Francisco, Boston, and elsewhere (4446). Our findings that 27% (32 of 118) of men who have sex with men from the SFGH HIV clinic and 39% (47 of 121) of those from Fenway Community Health had infections involving the buttocks, genitals, or perineum are consistent with sexual transmission of USA300 in this population. Cook and colleagues (47) recently reported MRSA infections involving the buttocks or genitoperineal area of heterosexual partners; these community-associated MRSA infections can progress to necrotizing fasciitis of the genitoperineal region (Fournier gangrene) (48). It is not clear whether the behavior potentiating these infections among men who have sex with men is anal sex (that is, dissemination of rectal carriage of community-associated MRSA), skin-abrading sexual practices, or increased frequency of intimate skin-to-skin contact; prevention messages may therefore need to suggest caution in each of these practices.

The risk for multidrug-resistant USA300 infections in the buttocks, genitals, or perineum was 30% (13 of 43) among SFGH HIV clinic patients and 47% (22 of 47) among Fenway Community Health patients, suggesting a similar role of sexual contact in the rapid dissemination of multidrug-resistant USA300. We also found that a patient treated at Fenway Community Health for infection with multidrug-resistant USA300 who had a history of frequent travel to and from the Castro District in San Francisco had a multidrug-resistant USA300 clone identical to that isolated from San Francisco patients. Since the beginning of the AIDS epidemic, sexual contact by men who have sex with men from Boston with partners from New York City, Los Angeles, and San Francisco has been associated with the dissemination of infectious pathogens (49). Because travel history is not frequently documented in patients' charts, it is not clear to what extent contacts between men who have sex with men from Boston and San Francisco could have contributed to the clonal dissemination of multidrug-resistant USA300. However, the genotype of multidrug-resistant USA300 in the patient from Fenway Community Health and the recent marked predominance of multidrug-resistant USA300 in Boston suggest that the multidrug-resistant USA300 epidemic probably started in San Francisco and has been disseminated by the frequent cross-coastal travel of men who have sex with men. The recent emergence of multidrug-resistant, community-associated MRSA with similar antimicrobial susceptibility profiles to multidrug-resistant USA300 was recently noted among men who have sex with men in New York City (32) and Los Angeles (Miller LG, Diep BA. Unpublished data.), indicating the potential for rapid, nationwide dissemination of multidrug-resistant USA300 among men who have sex with men.

The high incidence of multidrug-resistant USA300 among men who have sex with men has major implications for empirical treatment of skin infections in these patients. Several important antimicrobial classes for treatment of MRSA infections or eradication of colonization, including clindamycin, tetracycline, and mupirocin, may not be effective in this population. Resistance to trimethoprim–sulfamethoxazole and rifampin remains rare among USA300 isolates and was not seen in multidrug-resistant USA300 in our study (Table 1). However, prophylactic antimicrobial use has selected for the emergence of trimethoprim–sulfamethoxazole resistance in subclones genetically related to the USA300 lineage in patients from San Francisco and New York City who were infected with HIV (5052). Prudent use of these antimicrobial agents for suspected MRSA disease in men who have sex with men is advisable to slow the emergence of even more resistant community-associated MRSA. The pUSA03 plasmid that determines multidrug resistance in multidrug-resistant USA300 belongs to a highly promiscuous class of conjugative plasmids that could readily accept transposons encoding resistance to aminoglycosides, trimethoprim, vancomycin, and other antimicrobials, potentiating the emergence of even more resistant community-associated MRSA (28, 53).

Our study has limitations. Our incidence estimates for San Francisco come from a passive surveillance system and may underestimate the incidence of true infection. We relied on retrospective chart review for identification of risk factors for multidrug-resistant USA300 infection in the 2 clinic populations; because data were not collected or documented systematically, our estimates of risk may be influenced by selection, referral, documentation, or other biases. Specific sexual behaviors were not assessed or documented in clinic charts; we therefore cannot comment on the association between multidrug-resistant USA300 infection and specific male–male sexual practices. Finally, because the number of multidrug-resistant USA300 infection within risk factor subgroups was small, some of our higher estimates of risk are statistically compatible with more modest risk increases (that is, many of the CIs are wide and their lower bounds approach 1.0).

In summary, we show that multidrug-resistant USA300 has emerged as an important source of disease among men who have sex with men in 2 geographically distinct communities. The high proportion of infection involving the buttocks, genitals, and perineum suggests that community-associated MRSA may be transmitted in the setting of sexual contact among men who have sex with men. The link among USA300, multidrug-resistant USA300, and unsafe sexual risk behaviors should be evaluated further in prospective studies.

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King MD, Humphrey BJ, Wang YF, Kourbatova EV, Ray SM, Blumberg HM.  Emergence of community-acquired methicillin-resistant Staphylococcus aureus USA 300 clone as the predominant cause of skin and soft-tissue infections. Ann Intern Med. 2006; 144:309-17. PubMed
 
Hota B, Ellenbogen C, Hayden MK, Aroutcheva A, Rice TW, Weinstein RA.  Community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections at a public hospital: do public housing and incarceration amplify transmission? Arch Intern Med. 2007; 167:1026-33. PubMed
 
Gilbert M, MacDonald J, Gregson D, Siushansian J, Zhang K, Elsayed S. et al.  Outbreak in Alberta of community-acquired (USA300) methicillin-resistant Staphylococcus aureus in people with a history of drug use, homelessness or incarceration. CMAJ. 2006; 175:149-54. PubMed
 
Larsen A, Stegger M, Goering R, Sorum M, Skov R.  Emergence and dissemination of the methicillin resistant Staphylococcus aureus USA300 clone in Denmark (2000–2005). Euro Surveill. 2007; 12. PubMed
 
Ruppitsch W, Stoger A, Schmid D, Fretz R, Indra A, Allerberger F. et al.  Occurrence of the USA300 community-acquired Staphylococcus aureus clone in Austria. Euro Surveill. 2007; 12:071025.1. PubMed
 
Kearns AM, Ganner M, Hill RLR, East C, McCormick Smith I, Ganner MA. et al.  Community-associated MRSA ST8-SCCmecIVa (USA-300): experience in England and Wales. Oral presentation at the 17th European Congress of Clinical Microbiology and Infectious Diseases, Munich, Germany, 31 March–3 April 2007. Clin Microbiol Infect. 2007; 13:S27.
 
Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B. et al.  A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med. 2005; 352:468-75. PubMed
 
Hidron AI, Kourbatova EV, Halvosa JS, Terrell BJ, McDougal LK, Tenover FC. et al.  Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage. Clin Infect Dis. 2005; 41:159-66. PubMed
 
Adam H, McGeer A, Simor A.  Fatal case of post-influenza, community-associated MRSA pneumonia in an Ontario teenager with subsequent familial transmission. Can Commun Dis Rep. 2007; 33:45-8. PubMed
 
Christianson S, Golding GR, Campbell J, Mulvey MR, Canadian Nosocomial Infection Surveillance Program.  Comparative genomics of Canadian epidemic lineages of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2007; 45:1904-11. PubMed
 
Tinelli M, Pantosti A, Lusardi C, Vimercati M, Monaco M.  First detected case of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infection in Italy. Euro Surveill. 2007; 12:070412.1. PubMed
 
Wannet WJ, Heck ME, Pluister GN, Spalburg E, van Santen MG, Huijsdans XW. et al.  Panton-Valentine leukocidin positive MRSA in 2003: the Dutch situation. Euro Surveill. 2004; 9:28-9. PubMed
 
Huijsdens XW, van Santen-Verheuvel MG, Spalburg E, Heck ME, Pluister GN, Eijkelkamp BA. et al.  Multiple cases of familial transmission of community-acquired methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2006; 44:2994-6. PubMed
 
Hanssen AM, Fossum A, Mikalsen J, Halvorsen DS, Bukholm G, Sollid JU.  Dissemination of community-acquired methicillin-resistant Staphylococcus aureus clones in northern Norway: sequence types 8 and 80 predominate. J Clin Microbiol. 2005; 43:2118-24. PubMed
 
Tietz A, Frei R, Widmer AF.  Transatlantic spread of the USA300 clone of MRSA [Letter]. N Engl J Med. 2005; 353:532-3. PubMed
 
Gonzalez BE, Martinez-Aguilar G, Hulten KG, Hammerman WA, Coss-Bu J, Avalos-Mishaan A. et al.  Severe Staphylococcal sepsis in adolescents in the era of community-acquired methicillin-resistant Staphylococcus aureus. Pediatrics. 2005; 115:642-8. PubMed
 
Seybold U, Kourbatova EV, Johnson JG, Halvosa SJ, Wang YF, King MD. et al.  Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis. 2006; 42:647-56. PubMed
 
Haque NZ, Davis SL, Manierski CL, Vager D, Donabedian SM, Perri MB. et al.  Infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus(MRSA). Int J Antimicrob Agents. 2007; 30:72-7. PubMed
 
Miller LG, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer AS. et al.  Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. 2005; 352:1445-53. PubMed
 
Francis JS, Doherty MC, Lopatin U, Johnston CP, Sinha G, Ross T. et al.  Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis. 2005; 40:100-7. PubMed
 
Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG, Bridges CB. et al.  Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis. 2006; 12:894-9. PubMed
 
Campbell KM, Vaughn AF, Russell KL, Smith B, Jimenez DL, Barrozo CP. et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. J Clin Microbiol. 2004; 42:4050-3. PubMed
 
Coronado F, Nicholas JA, Wallace BJ, Kohlerschmidt DJ, Musser K, Schoonmaker-Bopp DJ. et al.  Community-associated methicillin-resistant Staphylococcus aureus skin infections in a religious community. Epidemiol Infect. 2007; 135:492-501. PubMed
 
Miller LG, Perdreau-Remington F, Bayer AS, Diep B, Tan N, Bharadwa K. et al.  Clinical and epidemiologic characteristics cannot distinguish community-associated methicillin-resistant Staphylococcus aureus infection from methicillin-susceptible S. aureus infection: a prospective investigation. Clin Infect Dis. 2007; 44:471-82. PubMed
 
.  Treatment of community-associated MRSA infections. Med Lett Drugs Ther. 2006; 48:13-4. PubMed
 
Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG. et al.  Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet. 2006; 367:731-9. PubMed
 
Carleton HA, Perdreau-Remington F.  A ten year survey of S. aureus isolates causing infections among gay men and people with HIV in San Francisco. Presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California; 27-30 September 2006:C2-1142.
 
Han LL, McDougal LK, Gorwitz RJ, Mayer KH, Patel JB, Sennott JM. et al.  High frequencies of clindamycin and tetracycline resistance in methicillin-resistant Staphylococcus aureus pulsed-field type USA300 isolates collected at a Boston ambulatory health center. J Clin Microbiol. 2007; 45:1350-2. PubMed
 
Szumowski JD, Cohen DE, Kanaya F, Mayer KH.  Treatment and outcomes of infections by methicillin-resistant Staphylococcus aureus at an ambulatory clinic. Antimicrob Agents Chemother. 2007; 51:423-8. PubMed
 
Shastry L, Rahimian J, Lascher S.  Community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections in men who have sex with men in New York City [Letter]. Arch Intern Med. 2007; 167:854-7. PubMed
 
Simmons T, O'Connell M.  Married-Couple and Unmarried-Partner Households: 2000. United States Census 2000. Accessed athttp://www.census.gov/prod/2003pubs/censr-5.pdfon 10 December 2007.
 
Mayer K, Appelbaum J, Rogers T, Lo W, Bradford J, Boswell S.  The evolution of the Fenway Community Health model. Am J Public Health. 2001; 91:892-4. PubMed
 
Clinical and Laboratory Standards Institute.  Methods for dilution antimicrobial susceptibility test for bacterial that grow aerobically. Approved standard. 7th ed. Document M7-A7. Wayne, PA: Clinical and Laboratory Standards Institute; 2006.
 
Tenover FC, McDougal LK, Goering RV, Killgore G, Projan SJ, Patel JB. et al.  Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006; 44:108-18. PubMed
 
Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE. et al.  Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol. 1999; 37:3556-63. PubMed
 
Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG.  Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 2000; 38:1008-15. PubMed
 
Groves R, Fowler F, Couper M, Lepkowski J, Singer E, Tourangeau R.  Survey Methodology. Hoboken, NJ: J Wiley; 2004.
 
Family Health Outcomes Project. Accessed athttp://www.ucsf.edu/fhopon 10 December 2007.
 
Ly LT, Revuelta MP, Hongo I, Kreiswirth BN, Davis S, Saltzman BR.  Clonal outbreak of community-acquired methicillin resistant Staphylococcus aureus skin abscesses in men who have sex with men in New York City: possible association with crystal methamphetamine usage [Abstract]. Presented at the annual meeting of the Infectious Diseases Society of America, Boston, 30 September–3 October 2004. Boston: Infectious Diseases Society of America; 2004: Abstract 490.
 
Lee NE, Taylor MM, Bancroft E, Ruane PJ, Morgan M, McCoy L. et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men. Clin Infect Dis. 2005; 40:1529-34. PubMed
 
Wener K, Gold HS, Wong M, Venkataraman L, Mayer KH, Cohen DE, et al.  High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization in an urban outpatient population [Abstract]. Presented at the 44th Annual Meeting of Infectious Diseases Society of America, Toronto, Ontario, Canada, 12-15 October 2006:Abstract 380. Accessed athttp://www.idsociety.org/WorkArea/showcontent.aspx?id=2092on 17 December 2007.
 
Scheer S, Chu PL, Klausner JD, Katz MH, Schwarcz SK.  Effect of highly active antiretroviral therapy on diagnoses of sexually transmitted diseases in people with AIDS. Lancet. 2001; 357:432-5. PubMed
 
Klausner JD, Kent CK, Wong W, McCright J, Katz MH.  The public health response to epidemic syphilis, San Francisco, 1999-2004. Sex Transm Dis. 2005; 32:S11-8. PubMed
 
Truong HM, Truong HH, Kellogg T, Klausner JD, Katz MH, Dilley J. et al.  Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting? Sex Transm Infect. 2006; 82:461-6. PubMed
 
Cook HA, Furuya EY, Larson E, Vasquez G, Lowy FD.  Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2007; 44:410-3. PubMed
 
Kalorin CM, Tobin EH.  Community associated methicillin resistant Staphylococcus aureus causing Fournier's gangrene and genital infections. J Urol. 2007; 177:967-71. PubMed
 
Mayer KH, Stoddard AM, McCusker J, Ayotte D, Ferriani R, Groopman JE.  Human T-lymphotropic virus type III in high-risk, antibody-negative homosexual men. Ann Intern Med. 1986; 104:194-6. PubMed
 
Martin JN, Rose DA, Hadley WK, Perdreau-Remington F, Lam PK, Gerberding JL.  Emergence of trimethoprim-sulfamethoxazole resistance in the AIDS era. J Infect Dis. 1999; 180:1809-18. PubMed
 
Shopsin B, Mathema B, Zhao X, Martinez J, Kornblum J, Kreiswirth BN.  Resistance rather than virulence selects for the clonal spread of methicillin-resistant Staphylococcus aureus: implications for MRSA transmission. Microb Drug Resist. 2000; 6:239-44. PubMed
 
Gordon RJ, Quagliarello B, Cespedes C, Chung M, de Lencastre H, Vavagiakis P. et al.  A molecular epidemiological analysis of 2 Staphylococcus aureus clonal types colonizing and infecting patients with AIDS. Clin Infect Dis. 2005; 40:1028-36. PubMed
 
Weigel LM, Clewell DB, Gill SR, Clark NC, McDougal LK, Flannagan SE. et al.  Genetic analysis of a high-level vancomycin-resistant isolate of Staphylococcus aureus. Science. 2003; 302:1569-71. PubMed
 
Appendix

We tested for multiresistance conjugative plasmid pUSA03 by using polymerase chain reaction assays designed to detect ermC, mupA, and the conjugative gene transfer genes traE and traI(28). These assays used the following oligonucleotides: mupA–F, 5′-CTTAGTTAACTCAGCATCAG-3′; mupA–R, 5′-GGTTTGATAGCGGCTCTATGC-3′; ermC–F, 5′-GAAATCGGCTCAGGAAAAGG-3′; ermC–R, 5′-GCTATTCACTTTAGGTTTAGGATG-3′; traE-F, 5′-AACAAATGCGTACTACAGACC-3′; traE–R, 5′-CCTGCTGTTGCTGTATCC-3′; traI–F, 5′-ACCGATATGAATAACACCGTC-3′; traI–R, 5′-AAACCTTCACAAGCAATGGAC-3′.

By using whole-plasmid DNA sequencing, we found that the pUSA03 plasmid from the Fenway Community Health patient with multidrug-resistant USA300 infection who had a frequent history of travel to and from the Castro District was identical in nucleotide sequence to the multiresistance pUSA03 found in multidrug-resistant USA300 isolates from San Francisco (GenBank Accession no. CP000258) (28). In brief, we prepared plasmid DNA by using the Qiagen Plasmid Midi Kit (Qiagen, Valencia, California). We sequenced 250 ng of plasmid DNA directly with 2.0 pmol of primers by using an Applied Biosystems 96-capillary 3730xl DNA Analyzers (DNA Sequencing Facility, University of California, Berkeley, California). Primers (n = 86) were designed to provide complete sequence coverage of the prototypical pUSA03 nucleotide sequence (28); these primers are described in detail in the Appendix Table.

Table Jump PlaceholderAppendix Table.  Primers Used in Sequencing of Multiresistance Conjugative Plasmid pUSA03

Figures

Grahic Jump Location
Figure.
Annual incidence of multidrug-resistant USA300 infection and percentage of male same-sex couples, by San Francisco ZIP code.

The key indicates the annual incidence of multidrug-resistant USA300 infection per 100 000 persons. The number within each ZIP code is the percentage of male same-sex couples, calculated by dividing the number of male same-sex, unmarried-partner households by the number of coupled (married and unmarried) households for each ZIP code, based on 2000 U.S. Census (Summary File 3) data (33). *Location of the San Francisco General Hospital HIV clinic.

Grahic Jump Location

Tables

Table Jump PlaceholderAppendix Table.  Primers Used in Sequencing of Multiresistance Conjugative Plasmid pUSA03
Table Jump PlaceholderTable 3.  Adjusted Relative Risk for Multidrug-Resistant USA300 Infections among Outpatients Treated at the San Francisco General Hospital HIV Clinic*
Table Jump PlaceholderTable 2.  Risk Factors for Multidrug-Resistant USA300 Infections among Outpatients in San Francisco and Boston*
Table Jump PlaceholderTable 1.  Distribution of Methicillin-Resistant Staphylococcus aureus Genotypes and Antimicrobial Resistance Profiles at the San Francisco General Hospital HIV Clinic

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References

Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB. et al.  Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. 2006; 355:666-74. PubMed
 
Diep BA, Carleton HA, Chang RF, Sensabaugh GF, Perdreau-Remington F.  Roles of 34 virulence genes in the evolution of hospital- and community-associated strains of methicillin-resistant Staphylococcus aureus. J Infect Dis. 2006; 193:1495-503. PubMed
 
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Hota B, Ellenbogen C, Hayden MK, Aroutcheva A, Rice TW, Weinstein RA.  Community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections at a public hospital: do public housing and incarceration amplify transmission? Arch Intern Med. 2007; 167:1026-33. PubMed
 
Gilbert M, MacDonald J, Gregson D, Siushansian J, Zhang K, Elsayed S. et al.  Outbreak in Alberta of community-acquired (USA300) methicillin-resistant Staphylococcus aureus in people with a history of drug use, homelessness or incarceration. CMAJ. 2006; 175:149-54. PubMed
 
Larsen A, Stegger M, Goering R, Sorum M, Skov R.  Emergence and dissemination of the methicillin resistant Staphylococcus aureus USA300 clone in Denmark (2000–2005). Euro Surveill. 2007; 12. PubMed
 
Ruppitsch W, Stoger A, Schmid D, Fretz R, Indra A, Allerberger F. et al.  Occurrence of the USA300 community-acquired Staphylococcus aureus clone in Austria. Euro Surveill. 2007; 12:071025.1. PubMed
 
Kearns AM, Ganner M, Hill RLR, East C, McCormick Smith I, Ganner MA. et al.  Community-associated MRSA ST8-SCCmecIVa (USA-300): experience in England and Wales. Oral presentation at the 17th European Congress of Clinical Microbiology and Infectious Diseases, Munich, Germany, 31 March–3 April 2007. Clin Microbiol Infect. 2007; 13:S27.
 
Kazakova SV, Hageman JC, Matava M, Srinivasan A, Phelan L, Garfinkel B. et al.  A clone of methicillin-resistant Staphylococcus aureus among professional football players. N Engl J Med. 2005; 352:468-75. PubMed
 
Hidron AI, Kourbatova EV, Halvosa JS, Terrell BJ, McDougal LK, Tenover FC. et al.  Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage. Clin Infect Dis. 2005; 41:159-66. PubMed
 
Adam H, McGeer A, Simor A.  Fatal case of post-influenza, community-associated MRSA pneumonia in an Ontario teenager with subsequent familial transmission. Can Commun Dis Rep. 2007; 33:45-8. PubMed
 
Christianson S, Golding GR, Campbell J, Mulvey MR, Canadian Nosocomial Infection Surveillance Program.  Comparative genomics of Canadian epidemic lineages of methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2007; 45:1904-11. PubMed
 
Tinelli M, Pantosti A, Lusardi C, Vimercati M, Monaco M.  First detected case of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infection in Italy. Euro Surveill. 2007; 12:070412.1. PubMed
 
Wannet WJ, Heck ME, Pluister GN, Spalburg E, van Santen MG, Huijsdans XW. et al.  Panton-Valentine leukocidin positive MRSA in 2003: the Dutch situation. Euro Surveill. 2004; 9:28-9. PubMed
 
Huijsdens XW, van Santen-Verheuvel MG, Spalburg E, Heck ME, Pluister GN, Eijkelkamp BA. et al.  Multiple cases of familial transmission of community-acquired methicillin-resistant Staphylococcus aureus. J Clin Microbiol. 2006; 44:2994-6. PubMed
 
Hanssen AM, Fossum A, Mikalsen J, Halvorsen DS, Bukholm G, Sollid JU.  Dissemination of community-acquired methicillin-resistant Staphylococcus aureus clones in northern Norway: sequence types 8 and 80 predominate. J Clin Microbiol. 2005; 43:2118-24. PubMed
 
Tietz A, Frei R, Widmer AF.  Transatlantic spread of the USA300 clone of MRSA [Letter]. N Engl J Med. 2005; 353:532-3. PubMed
 
Gonzalez BE, Martinez-Aguilar G, Hulten KG, Hammerman WA, Coss-Bu J, Avalos-Mishaan A. et al.  Severe Staphylococcal sepsis in adolescents in the era of community-acquired methicillin-resistant Staphylococcus aureus. Pediatrics. 2005; 115:642-8. PubMed
 
Seybold U, Kourbatova EV, Johnson JG, Halvosa SJ, Wang YF, King MD. et al.  Emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 genotype as a major cause of health care-associated blood stream infections. Clin Infect Dis. 2006; 42:647-56. PubMed
 
Haque NZ, Davis SL, Manierski CL, Vager D, Donabedian SM, Perri MB. et al.  Infective endocarditis caused by USA300 methicillin-resistant Staphylococcus aureus(MRSA). Int J Antimicrob Agents. 2007; 30:72-7. PubMed
 
Miller LG, Perdreau-Remington F, Rieg G, Mehdi S, Perlroth J, Bayer AS. et al.  Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus in Los Angeles. N Engl J Med. 2005; 352:1445-53. PubMed
 
Francis JS, Doherty MC, Lopatin U, Johnston CP, Sinha G, Ross T. et al.  Severe community-onset pneumonia in healthy adults caused by methicillin-resistant Staphylococcus aureus carrying the Panton-Valentine leukocidin genes. Clin Infect Dis. 2005; 40:100-7. PubMed
 
Hageman JC, Uyeki TM, Francis JS, Jernigan DB, Wheeler JG, Bridges CB. et al.  Severe community-acquired pneumonia due to Staphylococcus aureus, 2003-04 influenza season. Emerg Infect Dis. 2006; 12:894-9. PubMed
 
Campbell KM, Vaughn AF, Russell KL, Smith B, Jimenez DL, Barrozo CP. et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus infections in an outbreak of disease among military trainees in San Diego, California, in 2002. J Clin Microbiol. 2004; 42:4050-3. PubMed
 
Coronado F, Nicholas JA, Wallace BJ, Kohlerschmidt DJ, Musser K, Schoonmaker-Bopp DJ. et al.  Community-associated methicillin-resistant Staphylococcus aureus skin infections in a religious community. Epidemiol Infect. 2007; 135:492-501. PubMed
 
Miller LG, Perdreau-Remington F, Bayer AS, Diep B, Tan N, Bharadwa K. et al.  Clinical and epidemiologic characteristics cannot distinguish community-associated methicillin-resistant Staphylococcus aureus infection from methicillin-susceptible S. aureus infection: a prospective investigation. Clin Infect Dis. 2007; 44:471-82. PubMed
 
.  Treatment of community-associated MRSA infections. Med Lett Drugs Ther. 2006; 48:13-4. PubMed
 
Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG. et al.  Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet. 2006; 367:731-9. PubMed
 
Carleton HA, Perdreau-Remington F.  A ten year survey of S. aureus isolates causing infections among gay men and people with HIV in San Francisco. Presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, California; 27-30 September 2006:C2-1142.
 
Han LL, McDougal LK, Gorwitz RJ, Mayer KH, Patel JB, Sennott JM. et al.  High frequencies of clindamycin and tetracycline resistance in methicillin-resistant Staphylococcus aureus pulsed-field type USA300 isolates collected at a Boston ambulatory health center. J Clin Microbiol. 2007; 45:1350-2. PubMed
 
Szumowski JD, Cohen DE, Kanaya F, Mayer KH.  Treatment and outcomes of infections by methicillin-resistant Staphylococcus aureus at an ambulatory clinic. Antimicrob Agents Chemother. 2007; 51:423-8. PubMed
 
Shastry L, Rahimian J, Lascher S.  Community-associated methicillin-resistant Staphylococcus aureus skin and soft tissue infections in men who have sex with men in New York City [Letter]. Arch Intern Med. 2007; 167:854-7. PubMed
 
Simmons T, O'Connell M.  Married-Couple and Unmarried-Partner Households: 2000. United States Census 2000. Accessed athttp://www.census.gov/prod/2003pubs/censr-5.pdfon 10 December 2007.
 
Mayer K, Appelbaum J, Rogers T, Lo W, Bradford J, Boswell S.  The evolution of the Fenway Community Health model. Am J Public Health. 2001; 91:892-4. PubMed
 
Clinical and Laboratory Standards Institute.  Methods for dilution antimicrobial susceptibility test for bacterial that grow aerobically. Approved standard. 7th ed. Document M7-A7. Wayne, PA: Clinical and Laboratory Standards Institute; 2006.
 
Tenover FC, McDougal LK, Goering RV, Killgore G, Projan SJ, Patel JB. et al.  Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006; 44:108-18. PubMed
 
Shopsin B, Gomez M, Montgomery SO, Smith DH, Waddington M, Dodge DE. et al.  Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus strains. J Clin Microbiol. 1999; 37:3556-63. PubMed
 
Enright MC, Day NP, Davies CE, Peacock SJ, Spratt BG.  Multilocus sequence typing for characterization of methicillin-resistant and methicillin-susceptible clones of Staphylococcus aureus. J Clin Microbiol. 2000; 38:1008-15. PubMed
 
Groves R, Fowler F, Couper M, Lepkowski J, Singer E, Tourangeau R.  Survey Methodology. Hoboken, NJ: J Wiley; 2004.
 
Family Health Outcomes Project. Accessed athttp://www.ucsf.edu/fhopon 10 December 2007.
 
Ly LT, Revuelta MP, Hongo I, Kreiswirth BN, Davis S, Saltzman BR.  Clonal outbreak of community-acquired methicillin resistant Staphylococcus aureus skin abscesses in men who have sex with men in New York City: possible association with crystal methamphetamine usage [Abstract]. Presented at the annual meeting of the Infectious Diseases Society of America, Boston, 30 September–3 October 2004. Boston: Infectious Diseases Society of America; 2004: Abstract 490.
 
Lee NE, Taylor MM, Bancroft E, Ruane PJ, Morgan M, McCoy L. et al.  Risk factors for community-associated methicillin-resistant Staphylococcus aureus skin infections among HIV-positive men who have sex with men. Clin Infect Dis. 2005; 40:1529-34. PubMed
 
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Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

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Summary for Patients

Difficult-to-Treat Staphylococcal Infections in Men Who Have Sex with Men

The summary below is from the full report titled “Emergence of Multidrug-Resistant, Community-Associated, Methicillin-Resistant Staphylococcus aureus Clone USA300 in Men Who Have Sex with Men.” It is in the 19 February 2008 issue of Annals of Internal Medicine (volume 148, pages 249-257). The authors are B.A. Diep, H.F. Chambers, C.J. Graber, J.D. Szumowski, L.G. Miller, L.L. Han, J.H. Chen, F. Lin, J. Lin, T.H. Phan, H.A. Carleton, L.K. McDougal, F.C. Tenover, D.E. Cohen, K.H. Mayer, G.F. Sensabaugh, and F. Perdreau-Remington.

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