MAJOR ARTICLE

Population-Based Community Prevalence of Methicillin-Resistant Staphylococcus aureus in the Urban Poor of San Francisco Edwin D. Charlebois,1 David R. Bangsberg,1 Nicholas J. Moss,1 Matthew R. Moore,1 Andrew R. Moss,2 Henry F. Chambers,1 and Franc¸oise Perdreau-Remington1 1

Department of Medicine, Epidemiology and Prevention Interventions Center, Division of Infectious Diseases, San Francisco General Hospital, and 2Department of Epidemiology & Biostatistics, University of California, San Francisco

The study objective was to determine the prevalence and risk factors for nasal colonization with Staphylococcus aureus and methicillin resistance among the urban poor and to compare antibiotic resistance and genetic similarity to concurrently collected clinical isolates of methicillin-resistant S. aureus (MRSA). A populationbased community sample of 833 homeless and marginally housed adults were cultured and compared with 363 clinical isolates of MRSA; 22.8% of the urban poor were colonized with S. aureus. Of S. aureus isolates, 12.0% were methicillin resistant. Overall prevalence of MRSA was 2.8%. Significant multivariate risk factors for MRSA were injection drug use (odds ratio [OR], 9.7), prior endocarditis (OR, 4.1), and prior hospitalization within 1 year (OR, 2.4). Resistance to antimicrobials other than b-lactams was uncommon. Only 2 individuals (0.24%) with MRSA had no known risk factors. A total of 22 of 23 community MRSA genotypically matched clinical MRSA isolates, with 15 of 23 isolates identical to MRSA clones endemic among hospitalized patients. Recent reports of infection with methicillin-resistant Staphylococcus aureus (MRSA) in adults and children without known risk factors has led to concern that MRSA may be becoming a community-acquired pathogen [1–5]. One of the difficulties in assessing the incidence and prevalence of community-acquired MRSA (CA-MRSA)

Received 15 June 2001; revised 16 August 2001; electronically published 2 January 2002. Financial support: Centers for Disease Control and Prevention (Atlanta), California Emerging Infections Program, the University of California, San Francisco AIDS Clinical Research Program, National Institute of Mental Health, Bethesda, Maryland (grant R01-MH54907), and an unrestricted grant from Pharmacia & Upjohn, Peapack, New Jersey. E.D.C. and D.R.B. were supported in part by the Doris Duke Foundation, New York City. H.F.C. was supported in part by the USPHS and NIH/NIAID (grants AI43959 and AI46610). Reprints and correspondence: Dr. Edwin D. Charlebois, Dept. of Medicine, Division of Infectious Diseases, San Francisco General Hospital, University of California, San Francisco, 1001 Potrero Ave. UCSF 1372, Building 100, Rm. 303, San Francisco, CA 94110 ([email protected]). Clinical Infectious Diseases 2002; 34:425–33  2002 by the Infectious Diseases Society of America. All rights reserved. 1058-4838/2002/3404-0001$03.00

is the lack of accepted criteria for the definition of “community acquired.” It is often problematic to differentiate “health care–acquired” from true CA-MRSA, given the study design and sample populations reported in the literature. The potential establishment of MRSA infections in the community and the subsequent need to treat these infections with vancomycin raises the specter of the spread of vancomycin-resistant strains of S. aureus. This could lead to few or no treatment options for S. aureus infections. Indeed, the recent emergence of vancomycin intermediate-resistant S. aureus (VISA) in the United States and abroad is thought to have been driven by increasing vancomycin usage [6]. The single largest risk factor identified in studies elsewhere of CA-MRSA is hospitalization within the past 12 months [7–9]. It is also known that adults who acquire MRSA in the hospital may remain colonized for long periods of time [10, 11]. Injection drug use has also been reported to be a risk factor for CA-MRSA and carriage of S. aureus in a few urban settings [12–15].

MRSA in the Urban Poor • CID 2002:34 (15 February) • 425

Studies of the urban poor and the homeless have found that these populations have higher rates of hospitalization and a higher prevalence of HIV infection and injection drug use when compared with age-, race-, and sex-matched national averages [16–19]. In addition, crowded living conditions among the urban poor and poor access to sanitation facilities by street and shelter dwellers may place this population at particular risk for acquisition and transmission of S. aureus. Most reports and studies of CA-MRSA have been clinic- or hospital-based convenience samples. Because care-seeking populations are more likely to have illnesses than the general population, estimates derived from these populations suffer from selection bias and are not representative of the true community prevalence of S. aureus and CA-MRSA [20]. Several authors have expressed the need for population-based community studies of MRSA that use molecular genetic tools commonly used for infection control epidemiology [4, 21]. We therefore investigated the prevalence of and risk factors for nasal colonization with MRSA in a population-based, community sample of the urban poor in San Francisco, California, and compared antibiotic resistance patterns and genetic similarity between community samples of S. aureus and concurrently collected health care–identified MRSA isolates.

SUBJECTS AND METHODS Subject recruitment. By use of methods developed by the authors to study homeless and urban poor populations [16], 833 subjects were systematically sampled from the largest homeless shelters and free meal programs in San Francisco and a probability proportional-to-size sample of low-income single room occupancy hotels with a cost of !600 dollars per month. Subjects were recruited during August 1999–April 2000 during screening for a larger NIH funded study of HIV and tuberculosis in the urban poor. Nasal culture. Subjects were cultured by rotating a sterile dacron swab (BBL) into both nares and then directly inoculating a blood agar plate and streaked immediately for isolation of single colonies. Antibiotic susceptibility testing. Susceptibility to ampicillin, ciprofloxacin, tetracycline, gentamicin, erythromycin, cotrimoxazole, clindamycin, linezolid, and vancomycin were determined on Mueller-Hinton agar (BBL). The results were interpreted in accordance with the National Committee for Clinical Laboratory Standards guidelines (M100-S3). Susceptibility to methicillin was tested according to the recommendations of McDougal and Thornsberry [22]. Concurrent clinical samples. Concurrent clinical isolates of S. aureus and MRSA were obtained from the clinical microbiologic laboratory of the San Francisco Community Health Network (CHN). Antibiotic resistance data was electronically 426 • CID 2002:34 (15 February) • Charlebois et al.

collected for all isolates of S. aureus during August 1999–April 2000. Molecular typing. S. aureus isolates were molecularly typed by use of pulsed-field gel electrophoresis (PFGE). PFGE was obtained on all population-sampled MRSA (n p 23 ) and all clinical MRSA isolates collected from 1 August 1999 through 31 December 1999 (n p 125). Preparation of total DNA was performed as outlined by Goering and Deunsing [23] and PFGE as described by Maslow et al. [24]. The SmaI-digested fragments were resolved in 1% agarose in 0.5⫻ Tris-borate-EDTA buffer for 22 h at 14C and 6V/cm (Bio-Rad Laboratories). Gels were stained with ethidium bromide and imaged by UV transillumination with use of a gel imaging system (Bio-Rad Laboratories). Restriction-fragment analysis was performed as described by Tenover [25]. Isolates were considered indistinguishable (clonal) if they had exactly the same electrophoretic pattern and closely related if they differed by ⭐3 bands. PFGE genotypes were confirmed by application of multilocus restriction-fragment typing [26], a newly described technique in which allelic variation in the multilocus sequence typing housekeeping gene loci are detected by restriction-fragment pattern analysis rather than sequencing [27]. Statistical analysis. Prevalence and 95% confidence intervals were calculated by use of standard equations [28]. Fisher’s exact test was used to test for significant associations between categorical variables [29]. Odds ratios and significance testing for nasal carriage and methicillin resistance were obtained by use of logistic regression as implemented in the SAS statistical software package (version 8; SAS Institute) [30].

RESULTS Subject demographics and prevalence of S. aureus and methicillin resistance. Subject demographics and results of nasal culture and methicillin sensitivity testing in the community sample are given in table 1. Subjects were predominantly male (68.4%, n p 570), with 361 white (43.5%) and 332 black (39.9%). Other races accounted for 16.6% (n p 138) of the sample. The median age of the subjects was 44 years. Some 60.2% (n p 500) of the sample were “true homeless”—that is, had spent the last night in a shelter or on the street—and 39.7% (n p 331) were recruited from hotels. Of the 833 subjects tested, 190 (22.8%) of the sample were nasally colonized with S. aureus. Of those colonized with S. aureus, 12% (n p 23) were resistant to methicillin. Overall, the prevalence of nasal colonization with MRSA in the community sample was 2.8%. Colonization with S. aureus did not vary significantly by gender or homelessness. Study subjects age 150 years were less likely to be colonized with S. aureus than those age !50 years (16.1% [n p 35] vs. 25.3% [n p 152], P p .0062). White in-

Table 1.

Subject demographics and prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA).

P value

% MRSA of S. aureus (95% CI)

P value

Overall % MRSA (95% CI)

P value

—

12.0 (7.5–16.7)

—

2.8 (1.7–3.9)

—

.723

12.5 (6.8–18.2)

Subjects, no. (%)

S. aureus, a % (95% CI)

833 (100)

22.8 (20–25.6)

Male

570 (68.4)

22.5 (19.0–25.9)

Female

263 (31.6)

23.6 (18.5–28.7)

White

361 (43.5)

27.7 (23.1–32.3)

.004

13.0 (6.4–19.6)

Black

331 (39.9)

18.4 (14.3–22.6)

Reference

8.2 (1.3–15.0)

Other or mixed

138 (16.6)

20.3 (13.6–27.0)

.698

17.9 (3.7–32.0)

Reference

15.5 (6.2–24.8)

Characteristic Demographics All subjects Sex

1.0

11.3 (3.5–19.1)

2.8 (1.5–4.2)

1.0

2.7 (0.7–4.6)

Race

Reference

3.6 (1.7–5.5)

.096

1.5 (0.2–2.8)

Reference

3.6 (0.5–6.7)

.168

Age in years 18–29

51 (6.2)

30–39

216 (26.4)

26.9 (21–32.7)

27.5 (15.3–39.6)

14.3 (0–32.5)

40–49

334 (40.8)

24.0 (19.4–28.5)

50–77

218 (26.6)

16.1 ( 11.2–20.9)

.006

Positive

141 (17.0)

32.6 (24.6–40.3)

.003

Negative

686 (83.0)

20.6 (17.9–23.6)

Yes

500 (60.2)

23.2 (19.5–26.9)

No

330 (39.8)

22.4 (17.9–26.9)

3.9 (0–9.2) Reference

10.0 (3.5–16.5) 11.4 (0.9–21.9)

4.2 (1.5–6.8)

Reference

2.4 (0.8–4.0) 1.0

1.8 (0.1–3.6)

.472

2.1 (0–4.5)

.782

HIV antibody status 6.5 (0–13.6)

.205

14.2 (8.5–19.9)

2.9 (1.7–4.2)

Homeless .866

15.5 (9.0–22.1)

.109

6.8 (1.1–12.4)

3.6 (2.0–5.2)

.085

1.5 (0.2–2.8)

Injection drug use Ever injected drugs Yes

399 (47.9)

26.1 (21.8–30.4)

No

434 (52.1)

19.8 (16.1–23.5)

Yes

187 (22.4)

27.3 (20.9–33.6)

No

646 (77.6)

21.5 (18.4–24.7)

Yes

279 (16.8)

24.4 (19.4–29.4)

No

552 (33.2)

21.9 (18.5–25.4)

.038

20.2 (12.5–27.9)

!.001

2.3 (0–5.5)

5.3 (3.1–7.4)

!.001

0.5 (0–1.1)

Injected in past 30 days .113

23.5 (11.9–35.1)

.006

7.9 (3.4–12.4)

6.4 (2.9–9.9)

.002

1.7 (0.7–2.7)

History of abscess .431

20.6 (11.0–30.1)

.011

7.4 (2.8–12.1)

5.0 (2.5–7.6)

.007

1.6 (0.6–2.7)

Prior endocarditis Yes

30 (3.6)

26.7 (10.9–42.4)

No

797 (48.1)

22.7 (19.8–25.6)

Yes

463 (55.6)

24.6 (20.7–28.5)

No

370 (44.4)

20.5 (16.4–24.6)

Yes

345 (41.4)

24.3 (19.8–28.9)

No

488 (58.6)

21.7 (18.1–25.4)

Yes

182 (21.8)

22.0 (16.0–28.0)

No

651 (78.2)

23.0 (19.8–26.3)

Yes

371 (44.5)

25.6 (21.2–30.0)

No

462 (55.5)

20.6 (16.9–24.2)

.658

50.0 (15.5–84.5)

.009

10.5 (6.1–14.9)

13.3 (1.2–25.4)

.008

2.4 (1.3–3.4)

Health care contact Outpatient visit in past 12 months .184

13.2 (7.0–19.3)

.655

10.5 (3.7–17.4)

3.2 (1.6–4.8)

.400

2.2 (0.7–3.6)

Emergency room in past 12 months .402

13.1 (5.9–20.3)

.824

11.3 (5.3–17.3)

3.2 (1.3–5.0)

.528

2.5 (1.1–3.8)

Hospitalized in past 12 months .842

27.5 (13.7–41.3)

.002

8.0 (3.7–12.3)

6.0 (2.6–9.5)

.008

1.8 (0.8–2.9)

Antibiotics in past 12 months

a

95% CI based on the normal approximation.

.097

15.8 (8.5–23.1) 8.4 (2.9–14.0)

.181

4.0 (2.0–6.0) 1.7 (0.5–2.9)

.055

Table 2. isolates.

Antimicrobial resistance of community and concurrent clinical Staphylococcus aureus

% Resistant Organism

N

Em

Tet

Cpfx

Cm

Gm

TMP-SMX

Vm

LZD

167

35.3

5.4

1.8

2.4

0

13.2

0

0

MSSA Community sample MRSA Community sample

23

60.9

0

13

0

0

0

0

CHN: outpatient or !72 h

213

52.1

5.2

25.8

17.8

8.7

6.6

9.9

0

NT

CHN: nosocomial

150

91.3

2.0

79.3

76.0

13.3

8.0

0

NT

NOTE. CHN, community health network; Cm, clindamycin; Cpfx, ciprofloxacin; Em, erythromycin; Gm, gentamicin; LZD, linazolid; MRSA, methicillin-resistant S. aureus; MSSA, methicillin-susceptible S. aureus; NT, not tested; Tet, tetracycline; TMP-SMX, trimethoprim-sulfamethoxazole; Vm, vancomycin.

dividuals were significantly more likely to be colonized with S. aureus than black or those of other or mixed race (27.7% [n p 100] vs. 19.0% [n p 89], P ! .0034). Positive HIV antibody status was significantly associated with colonization with S. aureus (P p .0027) but not with MRSA. Methicillin resistance among those colonized with S. aureus and overall prevalence of MRSA did not differ significantly by sex, race, age, or HIV status. Injection drug use. Frequency of self-reported injection drug use and medical history of skin abscess and prevalence of S. aureus and methicillin resistance are presented in table 1. A medical history of ever having injected illegal drugs was significantly associated with colonization with S. aureus (P p .0386). Injection drug use within the preceding 30 days was not associated with colonization with S. aureus. Similarly, a history of a significant skin abscess was not associated with a higher prevalence of colonization with S. aureus. However, among those colonized with S. aureus, injection drug use, either a history or current use, was significantly associated with methicillin resistance (20.2% [n p 21] vs. 2.3% [n p 2], P ! .0001 and 23.5% [n p 11] vs. 8.0% [n p 12], P p .0057, respectively). History of a skin abscess was also significantly associated with methicillin resistance (P p .0107 ) among those colonized with S. aureus. Thirty individuals (3.6%) reported having a history of endocarditis, among which 21 (70%) also had a history of injection drug use. Prior endocarditis was significantly associated with methicillin resistance among those colonized (50% resistance in the endocarditis group vs. 10.5% methicillin resistance in the group without a history of endocarditis; P p .0077). In the community sample overall, statistically significant associations were found with higher prevalence of MRSA nasal colonization, both in past (P p .0001) and current (P p .0014) injection drug use, a medical history of an abscess (P p .0069) as well as prior endocarditis (P p .0077). Health care contact. Prevalence of nasal colonization with S. aureus and methicillin resistance by contact with the health428 • CID 2002:34 (15 February) • Charlebois et al.

care system and exposure to antibiotics in the preceding 12 months is given in table 1. The majority of subjects (56%, n p 463) in this community sample reported having had an outpatient healthcare visit within the preceding 12 months. Visits to the emergency room were also frequently reported, with 41.4% (n p 345) of subjects reporting at least 1 visit to the emergency room within the preceding 12 months. Colonization with S. aureus, methicillin resistance, and overall prevalence of MRSA were not significantly associated with a history of outpatient or emergency room visits. Hospitalization within the preceding 12 months was significantly associated with methicillin resistance and overall prevalence of MRSA in the community sample but not with colonization with S. aureus per se. Among those colonized with S. aureus, 27.5% (n p 11) of individuals with at least 1 hospitalization within the preceding 12 months had MRSA, as opposed to only 8% (n p 12) of those without hospitalization in the preceding year (P p .0020). Similarly, overall prevalence of MRSA was significantly higher among those with a history of hospitalization within the preceding 12 months (6.0% vs. 1.8%, P p .0078). Approximately 45% (n p 371) of the community sample reported having received an antibiotic within the preceding 12 months. The most common antibiotics reported were cephalexin, penicillin, tetracycline, and trimethoprim-sulfamethoxazole. However, specific recollection of antibiotic used was generally poor. Colonization, methicillin resistance, and overall prevalence of MRSA were marginally higher among those receiving antibiotics within the preceding 12 months, but the difference was not statistically significant. Antibiotic resistance patterns. Table 2 presents the results of the antibiotic sensitivity testing of the community-based nasal culture isolates and the concurrently obtained clinical MRSA isolates from the San Francisco CHN clinical laboratories. Among the methicillin-sensitive S. aureus isolates obtained from the community sample, significant resistance (⭓10% overall) was only seen for 2 of the tested antibiotics,

erythromycin (35%) and trimethoprim-sulfamethoxazole (12%). Among the community-based MRSA isolates, there was little resistance to other antibiotics classes. Only erythromycin and ciprofloxacin resistance were seen in 110% of the MRSA isolates. In contrast, a significant proportion of clinical MRSA isolates obtained from outpatients or within 72 h of hospital admission from the CHN healthcare system were resistant to 5 of 8 tested antibiotics. Nosocomial MRSA isolates were significantly more likely to be resistant to ⭓3 of the tested antibiotics than the community sample MRSA isolates (P p .003 ). More than 60% (n p 107) of the nosocomial isolates were resistant to erythromycin, ciprofloxacin, and clindamycin. None of the isolates obtained either from the community sample or from the CHN were resistant to vancomycin. No resistance to linezolid was seen. Risk factors for colonization and methicillin resistance. Univariate risk factors for colonization with S. aureus and methicillin resistance are presented in table 3. Significant risk factors for colonization with S. aureus in the community-based sample were positive HIV antibody status, white race (P p .0031), black race [protective effect OR !1] (P p .0155), age !50 years (P p .0058), and injection drug use (P p .0322). Literal homelessness (e.g., street or shelter dweller) was not associated with colonization with S. aureus. Significant, inde-

pendent risk factors for colonization with S. aureus identified by multivariate logistic regression were positive HIV antibody status (P p .006), age !50 years (P p .022), and white race (P p .0022). Among those colonized with S. aureus, significant univariate risk factors for methicillin resistance in the community sample were ever injecting drugs (P p .0018), history of prior endocarditis (P p .0041), history of prior abscess (P p .0106), having injected drugs within the preceding 30 days (P p .0051), and hospitalization within the preceding 12 months (P p .0015). There was a suggestion that homelessness also was associated with methicillin resistance among those colonized (OR, 2.54), however it was not statistically significant (P p .0789). When multivariate logistic regression was used, significant, independent risk factors for methicillin resistance among those colonized with S. aureus were ever injecting drugs (P p .0063) and hospitalization in the preceding 12 months (P p .0354). Several of the univariate risk factors for methicillin resistance were significantly correlated with one another. Race in this community sample was significantly associated with a history of ever injecting drugs. White individuals were more likely to have ever injected drugs (58.7%, n p 212 ) than those of other (49.3%, n p 68) or black race (36%, n p 119, P ! .001). Similarly, whites were more likely to have injected drugs within

Table 3. Risk factors for Staphylococcus aureus colonization, methicillin resistance, and methicillin-resistant S. aureus (MRSA) colonization.

OR (95% CI)

P value

Adjusted OR (95% CI)

P value

HIV-positive antibody

1.87 (1.3–2.8)

.002

1.77 (1.2–2.7)

.006

Age !50 years

1.77 (1.2–2.7)

.0058

1.62 (1.1–2.5)

.022

White

1.64 (1.2–2.3)

.0031

1.69 (1.2–2.4)

.0022

Ever used injection drugs

1.43 (1.0–2.0)

.0322

Black

0.66 (0.5–0.9)

.0155 8.3 (1.8–37)

.0063

2.7 (1.1–7.2)

.0354

Outcome, risk factor Colonization with S. aureus

Methicillin resistance among colonized Ever used injection drugs

10.0 (2.4–46)

.0018

Prior endocarditis

8.53 (2.0–37)

.0041

Hospitalized in past 12 months

4.36 (1.8–11)

.0015

Injected drugs in past 30 days

3.58 (1.5–8.8)

.0051

Prior abscess

3.23 (1.3–8.0)

.0106

Homeless

2.54 (0.9–7.2)

.0789

Colonization with MRSA Ever used injection drugs

12.0 (2.8–51)

.0008

9.70 (2.2–42)

.0024

Prior endocarditis

6.30 (2.0–19)

.0017

4.05 (1.2–13)

.0214

Used injection drugs in past 30 days

3.96 (1.7–9.1)

.0012

Hospitalized in past 12 months

3.40 (1.5–7.9)

.0039

2.43 (1.0–5.7)

.0432

Prior abscess

3.19 (1.4–7.5)

.0075

Antibiotics used in past 12 months

2.39 (1.0–5.7)

.0493

Homeless

2.43 (0.9–6.6)

.0824

MRSA in the Urban Poor • CID 2002:34 (15 February) • 429

Figure 1. Pulsed-field gel electrophoresis of the 23 community-sampled methicillin-resistant Staphylococcus aureus. The 6 genotypes and 14 subtypes were obtained after SmaI digestion. Lanes 15a and 15b as well as 19a and 19b represent 2 isolates from the same patient.

the preceding 30 days (29.1%, n p 105) than those of other (22.5%, n p 31) or black race (15.4%, n p 51, P ! .001). Individuals with a history of past injection drug use were significantly more likely to have been hospitalized in the preceding 12 months (61.5% [n p 112] among injectors vs. 44.1% [n p 287], P ! .001) among noninjectors and have a history of prior skin abscess (53.8% [n p 214] among injectors vs. 15.0% [n p 65] among noninjectors, P ! .001 ). Persons with a history of prior abscess were more likely to have been hospitalized in the preceding 12 months (30.5%, n p 85) than those without a history of prior abscess (17.6%, n p 97 , P ! .001). A history of prior endocarditis was also associated with injection drug use (P p .0155) and hospitalization within the preceding 12 months (P p .022). Risk factors among the community sample colonized with MRSA. Among the 23 community-sample individuals colonized with MRSA, 21 (91%) had a history of injection drug use, 12 (52%) had injected within the preceding 30 days, and 14 (61%) had a history of abscess. Fifteen subjects (65%) re430 • CID 2002:34 (15 February) • Charlebois et al.

ported receiving an antibiotic in the preceding 12 months, and 11 (48%) had been hospitalized in the past year. A history of endocarditis was reported by 4 (17%) of 23 patients colonized with MRSA, and 3 of 4 (13% of MRSA) were HIV antibody positive. Only 2 individuals with MRSA reported no known risk factors for methicillin resistance. Both subjects had MRSA isolates that were sensitive to all tested antibiotics. The overall prevalence of MRSA in subjects without known risk factors in this population was 2 (0.24%) of 833 (95% exact Poisson CI, 0.029%–0.87%). Genotyping of MRSA isolates from the community. PFGE of the 23 MRSA isolates recovered from the community is presented in figure 1. A total of 6 distinct DNA genotypes (G1–G6) and 14 subtypes were identified after SmaI digestion. Two (8.6%) of 23 isolates had a unique genotype (G5 and G6). Four subtypes (G1c, G2b, G2c, and G4) were seen in 11 community isolate. Genotype G1 accounted for 10 isolates (43.5%), genotype G2 for 5 isolates (21.7%), genotypes G3 and G4 for 3 isolates (13%). Seven isolates belonging to genotype G1 had

identical PFGE profiles (G1a), and 4 further subtypes (G1b–e) each represented 1 isolate. Genotypes G2 and G3 were each divided in 3 subtypes, G2a (n p 1), G2b (n p 2), and G2c (n p 2) subtypes and (G3a, G3b, and G3c) with 1 isolate in each group. Genotype G4 represented 3 identical PFGE profiles. Comparison of the community-based MRSA genotypes with genotypes obtained from concurrently collected clinical MRSA isolates from the CHN revealed matches for all but 1 of the community isolates (G6). Genotype/subtypes G1a, G1c, and G3c were found to match strains of MRSA that were endemic among hospitalized patients. Some subtypes within a genotype (G1c) were seen predominantly among heath care–sampled clinical MRSA isolates present among outpatient, clinic-based samples but rarely among hospitalized patients. One community sample genotype (G6) was not found to match any of the MRSA isolates obtained from the concurrent CHN heath care sample. Susceptibility of MRSA to other antimicrobials. Community isolates identified as genotypes G4 and G5 and subtypes G1b and G1e were only resistant to methicillin. The majority of the community isolates identified as genotype G1, subtypes (G1a, G1c, and G1d) were resistant to erythromycin alone, as were most hospital strains recovered during that same period that matched genotypes G1a, G1c, and G1d. One G1a isolate from the community was additionally resistant to ciprofloxacin. Four of 5 strains identified as genotype G2 also showed only erythromycin resistance. Hospital isolates identical to the G2a genotype carried an additional resistance to tetracycline. One strain recovered from the community (lane 1) was also resistant to ciprofloxacin. The community strain identified as G3a was only resistant to erythromycin, whereas subtypes of genotype G3b and G3c were multidrug resistant and showed ciprofloxacin, clindamycin, and erythromycin resistance. The susceptibility profiles of hospital-identified strains were identical to the matching community strains of the same genotype/subtype. Community isolates of genotype G4 were multidrug susceptible and again were comparable in resistance profile with hospital strains recovered during the same time period. The community isolate identified as genotype G5 was multidrug sensitive (resistant only to methicillin), whereas other MRSA isolates of genotype G5 derived from the hospital carried resistance to gentamicin, ciprofloxacin, clindamycin, and erythromycin. Genotype G6, the only genotype without a genetic match to hospital-based clinical samples, was sensitive to all antimicrobials except penicillin and cephalosporins. There was no correlation between risk factors and colonization with a specific genotype. Two of 4 patients identified with MRSA and reporting an history of endocarditis had culture specimens available from 1996 and 1997 for genotyping. One

subject was colonized with a genotype identical to the endocarditis isolate, 4 years after the event.

DISCUSSION We present here the first population-based study of the prevalence and risk factors for nasal colonization with S. aureus and methicillin resistance in a community sample of the urban poor. Previous investigators have estimated the prevalence of community-acquired MRSA through convenience samples of outpatient populations or persons presenting at hospital admission. Evaluation of risk factors in these studies was most often retrospective and record-based. In those studies, estimates of methicillin resistance among those colonized with S. aureus range from 11.9% in a dermatology outpatient clinic in Houston to 25% among patients presenting for hospitalization at 5 Pittsburgh–area hospitals [31–33]. In an attempt to avoid the selection bias inherent in careseeking populations, several studies have focused on healthy individuals. In a study of healthy pediatric clinic patients and their guardians in New York City, Shopsin et al. [2] found that, among 500 subjects the prevalence of nasal carriage of S. aureus was 35% for children and 28% for guardians. Among those colonized, only 1 individual was found to harbor MRSA (0.26%), and a predisposing risk factor was noted to be present. Again finding a low prevalence of MRSA in healthy populations, Sa´-Lea˜o et al. [34] in Portugal found !1% MRSA carriage in a study of 823 Air Force draftees, 225 nonmedical university students, 107 high school students, and 2111 children in daycare centers. Comparison of these study results from healthy persons with those from general care–seeking populations show the magnitude of the selection bias in the estimate of the prevalence of community-acquired MRSA when sampling careseeking populations. The results of our population-based community sample of the urban poor in San Francisco fit in well with the results from the few large surveys of healthy populations. Although the urban poor and homeless are often subjected to crowded living conditions and have poor access to sanitation facilities, we found that colonization rates with S. aureus among this population to be similar to that which has been reported for the general population. HIV infection (estimated to be 13% in this population) was associated with an increased risk of colonization with S. aureus, as has been reported elsewhere in the literature [35]. However, HIV was not associated with a higher prevalence of MRSA. The prevalence of methicillin resistance among those colonized with S. aureus in our study was 11%, significantly lower than the proportion of S. aureus isolates that are methicillin resistant seen in hospitalized, outpatient, and care-seeking populations. The overall prevalence of MRSA in individuals without known risk factors in our study was 0.24%, MRSA in the Urban Poor • CID 2002:34 (15 February) • 431

very similar to the results in healthy children and guardians in New York City (0.26%) and in the large sample of the Portuguese population (0.06%). The present study identifies the importance of injection drug use as a significant risk factor for community colonization with MRSA among the urban poor. This finding confirms the increased risk associated with injection drug use seen in a casecontrol studies of hospitalized patients during an outbreak of “community-acquired” MRSA in 40 patients in the early 1980s in Detroit [15, 36]. Injection drug use may serve to elevate the risk of MRSA secondary to increased rates of hospitalization and exposure to antibiotics arising from complications of drug use such as frequent skin abscesses, bacteremias, and endocarditis. The present study also confirms previous findings in the literature that hospitalization within the past year is a significant risk factor for colonization with MRSA and that community acquired or, more precisely, community-identified MRSA infections are primarily multidrug sensitive. One strength of this study is that information about health-care use and risk factors was obtained through direct interview of study subjects along with electronic data collection from the San Francisco CHN. It is clear from our data that clinical MRSA samples obtained from health care settings are more likely to be multidrug resistant than MRSA obtained in the community. However, the molecular typing data and the epidemiologic risk factors from this study imply a close relationship between community and hospital strains of MRSA. Given the high proportion of our community-identified MRSA isolates that genetically match endemic MRSA clones present in CHN-hospitalized patients and the strong risk factor for MRSA of prior hospitalization within the past year, it seems likely that these community-identified MRSA infections were acquired from contact with the health care system. What then explains the difference in antibiotic resistance patterns between community-identified MRSA and health care–identified MRSA? We speculate that 3 factors may be at work: (1) more drug-resistant clones (as found in hospitalized patients) may be less fit and less likely to persist than susceptible clones in the absence of selective pressure of antibiotic exposure as occurs in the hospital setting; (2) acquisition of resistance by relatively susceptible clones in the intensive selective pressure of the hospital; and (3) loss of resistance determinants in the absence of selective pressure. Why resistance to methicillin persists whereas resistances to other antibiotics is lost could reflect either the selective pressure of repeated b-lactam exposure (blactam antibiotics being the commonly preferred agent for empiric therapy of staphylococcal infections in the outpatient setting) or possibly the presence of compensatory mutations that favor maintenance of mecA [37]. Serial sample collection and molecular study of a cohort of hospitalized patients with MRSA who then move into the community may be able to show the 432 • CID 2002:34 (15 February) • Charlebois et al.

selective loss or gain of resistance genes responsible for resistance to agents other than methicillin. Although several small clusters of apparent community transmission of MRSA suggest that MRSA may be evolving into a community-acquired pathogen, large community-based prevalence studies, such as the one presented here, provide evidence that MRSA in individuals without known risk factors is, at present, rare. Overall prevalence of MRSA among the urban poor in our samples was reflective of the high proportion of individuals hospitalized in the previous 12 months. Given the rising proportion of nosocomial S. aureus infections that are resistant to methicillin and other common antibiotics and the specter of VISA along with the frequent hospitalization in this population, it is not unlikely that a higher community prevalence of MRSA and the emergence of VISA will be seen in the future in this community.

Acknowledgments

We acknowledge the contributions of Dr. Sharon Perry, Ellen Stein, Jennifer Perlman, Priscilla Martinez, Arlette Monlina, John Day, Blackberry, Omer Pasi, and Jay Jankowski to the collection of interview data and of Laurae Pearson for manuscript preparation

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