Prevalence of and Risk Factors for Methicillin-Resistant Staphylococcus aureus (MRSA) Nasal Colonization in HIV-Infected Ambulatory Patients

Cenizal, Mary Jo MD*†; Hardy, Robert D MD*; Anderson, Marc BS*; Katz, Kathy BS‡; Skiest, Daniel J MD§

JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0b013e31817e9b79
Clinical Science

Background: Estimates of the prevalence of colonization with methicillin-resistant Staphylococcus aureus (MRSA) vary in HIV-infected patients.

Methods: HIV clinic patients were prospectively cultured. Bilateral nasal and axillary swabs were plated on BBL CHROMagar MRSA media. Molecular typing was done by pulse-field gel electrophoresis, and staphylococcal cassette chromosomemec typing was determined. A patient questionnaire was conducted to ascertain potential MRSA risk factors; medical records were reviewed.

Results: Fifteen of 146 (10.3%) patients had MRSA nasal colonization; 1 also had axillary colonization. Twelve of 15 isolates were staphylococcal cassette chromosomemec type IV, and 8 of 14 were USA300 or USA400 genotype. MRSA colonization was associated with lower CD4 cell count, not receiving current or recent antibiotics, history of prior MRSA or methicillin-susceptible Staphylococcus aureus infection (P < 0.05 for all), and a trend toward history of hospitalization or emergency department visit in the past year (P = 0.064). Current use of trimethoprim-sulfamethoxazole was protective for colonization: 0 of 29 trimethoprim-sulfamethoxazole recipients were colonized versus 15 of 117 nonrecipients, P = 0.04. In a multivariate logistic regression model, prior infection with either methicillin-susceptible S. aureus (odds ratio = 32.4, 95% confidence interval 3.04 to 345.42) or MRSA (odds ratio = 9.71, 95% confidence interval 2.20 to 43.01), not receiving current or recent antibiotics (odds ratio = 0.026, 95% confidence interval 0.002 to 0.412), and lower CD4 count (odds ratio 0.996, 95% confidence interval 0.992 to 0.999) were associated with MRSA colonization.

Discussion: The prevalence of MRSA nasal colonization was relatively high compared with prior studies; axillary colonization was rare. Prior staphylococcal infection (methicillin-susceptible S. aureus or MRSA), not receiving antibiotics, and lower CD4 count were associated with MRSA nasal colonization. Trimethoprim-sulfamethoxazole seemed to be protective of MRSA colonization.

Author Information

From the *Division of Infectious Diseases, The University of Texas Southwestern Medical Center, Dallas, TX; †Casa Grande Regional Medical Center, Casa Grande, AZ; ‡Division of Pediatric Infectious Diseases, The University of Texas Southwestern Medical Center, Dallas, TX; and §Division of Infectious Disease, Baystate Medical Center, Springfield, MA.

Received for publication November 16, 2007; accepted May 2, 2008.

Correspondence to: Daniel J. Skiest, MD, Division of Infectious Diseases, Baystate Medical Center, 759 Chestnut Street, Springfield, MA 01199 (e-mail:

Article Outline
Back to Top | Article Outline


Numerous studies have documented an increase in community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in patients lacking traditional methicillin-resistant Staphylococcus aureus (MRSA) risk factors.1-5 A high rate of CA-MRSA infection in HIV-infected individuals has also been observed recently.6-11 As with non-HIV-infected patients, most of the CA-MRSA infections have involved skin and/or soft tissue.7-10

The primary reservoir of S. aureus is the anterior nares. Approximately 22%-38% of healthy individuals are colonized with methicillin-susceptible Staphylococcus aureus (MSSA).12-16 Colonization frequently precedes infection with MSSA and/or health care-associated MRSA.16,17 The rate of colonization with MRSA has been relatively low: 0.8%-3% in prior studies in the general population,12-15 although recent studies indicated that it may be increasing in certain locales among children (9% in Nashville, TN).18

The prevalence of nasal colonization with S. aureus in HIV infection seems to be in the same range as the general population,19-23 with some studies showing a somewhat higher rate.16,24-27 Some have suggested that HIV may be an independent risk for S. aureus nasal colonization.22,24,25,27 Prior studies have indicated that the prevalence of MRSA colonization in HIV-infected patients is between 0% and 17%.19-25,28 However, these studies were largely conducted before the explosion of CA-MRSA in the community.

As the role of nasal colonization with CA-MRSA is not well established, we decided to undertake a prospective study. Our objectives were to determine the prevalence of MRSA colonization in HIV-infected individuals and to identify demographic and clinical factors that correlate with MRSA nasal colonization in this population.

Back to Top | Article Outline


The population for this prospective study was drawn from the HIV clinic of Parkland Hospital in Dallas, Dallas, TX. The clinic provides comprehensive HIV primary care to approximately 4000 patients. Eligible patients were HIV seropositive, active clinic patients who presented to the HIV clinic in July or August 2005 for a routine clinic visit and who were willing to participate in the study including completion of a questionnaire and consent to cultures. Exclusions from the study included non-English-speaking patients (if no interpreter was available at that time).

Nasal samples were obtained from both anterior nares and both axilla using a culturette swab (BBL CultureSwab, BBL Microbiology Systems; Becton Dickinson, Sparks, MD). One swab was used for both anterior nares, and a separate swab was used to culture both axillae. Swabs were not premoistened. Swabs were plated on “BBL CHROMagar MRSA” media (Becton Dickinson). This media is a selective and differential medium for qualitative direct detection of nasal colonization with MRSA and has been previously validated for this purpose (BD BBL CHROMagar MRSA package insert; Becton Dickinson, Sparks, MD). Culture plates were incubated at 36°C for 48 hours. Growth of bacterial colonies consistent with MRSA on the CHROMagar plates was then confirmed by the Staphaurex test (Murex Biotech Limited), which tests for the presence of coagulase and/or protein A.

DNA of the MRSA strains was digested with Sma 1 and separated by pulse-field gel electrophoresis using the CHEF-DR II system (Bio-Rad, Hercules, CA) as previously described.29 Characterization of the staphylococcal cassette chromosome (SCC)mec type of each isolate was determined using multiplex polymerase chain reaction methods30; type IV subtypes were determined according to methods described by Okuma.31

A questionnaire was conducted to ascertain risks associated with MRSA colonization. Medical records were reviewed to document laboratory and clinical data. The study was approved by the Institutional Review Board of the University of Texas Southwestern Medical Center, and informed consent was obtained from all patients. Statistical analysis was performed with SPSS for windows. Adjusted odds ratios and 95% confidence intervals were computed in a forward stepwise logistic regression model incorporating variables that were significant (at <0.2 level) on χ2 test.

Back to Top | Article Outline


One hundred forty-six patients were enrolled: median age 42 years (range 21-71). There were 122 males: 45% were African American, 42% white, and 12% Hispanic. The primary HIV risk category was male-male sex in 91 (62%), injecting drug use in 29 (20%), and other or not specified in 26 (18%). The median CD4 count was 328 cells/mm3. The mean HIV viral load was 56,213 copies/mL (median < 400). Twenty-nine (20%) patients were receiving trimethoprim-sulfamethoxazole (T/S).

Fifteen of 146 (10.3%) patients had a positive nasal swab for MRSA. One of 146 (0.7%) had a positive axillary swab for MRSA; this patient also had nasal colonization. Patients colonized with MRSA had lower CD4 cell counts and were less likely to be receiving antibiotics currently or in the past 6 months (recent antibiotics). Among patients receiving recent antibiotics, 38 of 43 received an antibiotic with potential activity versus MRSA including T/S in 29. Colonized patients were more likely to have had prior MRSA or MSSA infection (Table 1). Current use of T/S was protective for colonization: 0 of 29 T/S recipients were colonized with MRSA versus 15 of 117 patients not receiving T/S, P = 0.04. There was a trend toward association with nasal colonization for hospitalization or emergency department visit in the past year (P = 0.064). Most recent HIV viral load, use of nasal corticosteroids, documented skin disease (past or present) (eg, folliculitis, psoriasis), current receipt of highly active antiretroviral therapy (HAART), HIV risk factor, or incarceration (past or present) were not associated with MRSA nasal colonization. In a multivariate logistic regression model, prior infection with MSSA or MRSA and lower CD4 count were each associated with MRSA colonization whereas recent antibiotics were negatively associated with MRSA nasal colonization (Table 1).

Twelve of 15 MRSA isolates tested were SCCmec type IV whereas 1 isolate was type I and 2 were type II (Table 2). Pulse-field gel electrophoresis profiles were conducted on 13 of 15 isolates, and the patterns were consistent with the USA100 strain in 1 isolate, USA300 in 7 isolates, USA400 in 1 isolate, USA500 in 3 isolates, and USA800 in 1 isolate. Of the 5 patients with USA100, USA500, or USA800, 4 had been hospitalized in the past 12 months whereas 8 of 9 patients with USA300 or USA400 were not hospitalized in the past 12 months.

Back to Top | Article Outline


We determined the prevalence of MRSA nasal colonization among ambulatory HIV-infected patients to be 10%. This rate of nasal colonization is higher than previous studies conducted before the rapid increase in CA-MRSA.16,19-23,25,26 HIV infection is an independent risk for MRSA nasal colonization.24,27,32 A prevalence of MRSA nasal colonization of 10% in this population with a high rate of MRSA skin and/or soft tissue infections (SSTIs)33 suggests a poor correlation between nasal colonization and SSTI in CA-MRSA.

As expected in this outpatient population, the majority of strains contained SCCmec type IV, which is most common in CA-MRSA strains and is associated with less antibiotic resistance versus other SCCmec types. The majority of MRSA colonization was with community-associated strains, for example, USA300 or USA400. However, several isolates were health care-associated strains, for example, USA100, USA500, and USA800 clones. As expected, the non-community-associated strains were those associated with health care exposure; all but one of these patients had recently been hospitalized.

Although the role of health care-associated MRSA nasal colonization in subsequent infections is accepted, the role of colonization with CA-MRSA in subsequent infections is not. The pathogenesis of infection with CA-MRSA may be different compared with infection with MSSA or health care-associated MRSA. It is not known if the CA-MRSA strains harbored in the anterior nares of individuals are the same strains causing infection or whether other sites are colonized (eg, vagina, rectum, skin).34 CA-MRSA strains may be more likely to result in infection compared with MSSA strains.35,36 Recent studies of CA-MRSA infection have suggested a role of direct contact with patients or materials colonized with CA-MRSA.9,37 Alternatively, patients colonized with MRSA may be more prone to subsequent MRSA infection (compared with those colonized with MSSA).35,38

Our study found a very low prevalence of MRSA axillary colonization (0.7%). It is unlikely that axillary colonization with MRSA is important in the pathogenesis of CA-MRSA infections in HIV-infected individuals. A recent study found that 12% of patients had S. aureus throat colonization in the absence of nose colonization.39 The role of colonization of the throat and other body sites should be investigated in future studies.

Lower CD4 count was associated with higher MRSA colonization risk in multivariate analysis. Lower CD4 count has also been previously demonstrated to be a risk for MRSA colonization.20,23 It is not clear if lower CD4 count independently correlates with an increased risk for nasal colonization or if it is associated with other factors. For example, patients with lower CD4 cell counts may be more likely to have had prior staphylococcal infections.

Prior infection with either MRSA or MSSA was associated with MRSA nasal colonization in the multivariate model. Although it seems straightforward why prior MRSA infection might increase risk of subsequent colonization, for example, it is known that some patients are persistent carriers and it is not clear why prior MSSA was associated with colonization. It is possible that persons predisposed to persistent carriage with S. aureus may have MRSA replace the niche formerly occupied by MSSA. Recurrence of MRSA SSTIs is common6 and may be partially explained by persistent colonization (either nasal or other site).38,40 A previous study that included both HIV-infected and noninfected patients demonstrated prior MRSA colonization or infection to be a predictor of nasal colonization.24 Whether eradication of MRSA colonization is beneficial in prevention of future infections is not clear.

Receipt of current or recent antibiotics was associated with a low rate of MRSA colonization. Eighty-eight percent of these patients received antibiotics with potential MRSA activity including T/S in the majority. Prior studies have shown a protective effect of antistaphylococcal antibiotics on staphylococcal nasal colonization.19,25 Previous studies have confirmed the protective effect of T/S on CA-MRSA infections.9,10 CA-MRSA isolates are almost universally susceptible to T/S. Thus, the protective effect of T/S on MRSA nasal colonization is not unexpected and represents an additional benefit to T/S prophylaxis in addition to the well-established benefit for prevention of Pneumocystis jirovecii pneumonia.

Limitations of our study are that we do not have longitudinal data on the subsequent clinical course of our cohort to ascertain the rate of MRSA infection. It would also be of interest to look at colonization over time to determine if persistent colonization results in a higher infection rate than transient colonization. In addition, we may have potentially excluded some Spanish-speaking patients. This could have affected the ethnic makeup of the cohort. However, the ethnicity of the population we studied was reflective of the overall HIV clinic population. Finally, it would have been of interest to know the overall S. aureus (MSSA and MRSA) nasal colonization rate in this cohort.

In conclusion, we determined the prevalence of nasal colonization with MRSA in an ambulatory HIV-infected population to be 10%. Prior staphylococcal infection (MSSA or MRSA), more advanced immunodeficiency, and not receiving current antibiotics (primarily T/S) correlated with current MRSA colonization. Future studies should address the role of nasal colonization and other body sites on subsequent infection and the utility of decolonization.

Back to Top | Article Outline


1. Salgado CD, Farr BM, Calfee DP. Community-acquired methicillin-resistant Staphylococcus aureus: a meta-analysis of prevalence and risk factors. Clin Infect Dis. 2003;36:131-139.
2. Gorak EJ, Yamada SM, Brown JD. Community-acquired methicillin-resistant Staphylococcus aureus in hospitalized adults and children without known risk factors. Clin Infect Dis. 1999;29:797-800.
3. Herold BC, Immergluck LC, Maranan MC, et al. Community-acquired methicillin-resistant Staphylococcus aureus in children with no identified predisposing risk. JAMA. 1998;279:593-598.
4. Bukharie HA, Abdelhadi MS, Saeed IA, et al. Emergence of methicillin-resistant Staphylococcus aureus as a community pathogen. Diagn Microbiol Infect Dis. 2001;40:1-4.
5. Morin CA, Hadler JL. Population-based incidence and characteristics of community-onset Staphylococcus aureus infections with bacteremia in 4 metropolitan Connecticut areas, 1998. J Infect Dis. 2001;184:1029-1034.
6. Skiest D, Brown K, Hester J, et al. Community-onset methicillin-resistant Staphylococcus aureus in an urban HIV clinic. HIV Med. 2006;7:361-368.
7. Bar A, Hantschke D, Mirmohammadsadegh A, et al. Spectrum of bacterial isolates in HIV-positive patients with skin and soft tissue infections: emergence of methicillin-resistant Staphylococci. AIDS. 2003;17:1253-1256.
8. Anderson EJ, Hawkins C, Bolon MK, et al. A Series of skin and soft tissue infections due to methicillin-resistant Staphylococcus aureus in HIV-infected patients. J Acquir Immune Defic Syndr. 2006;41:125-127.
9. Lee NE, Taylor MM, Bancroft E, 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;40:1529-1534.
10. Mathews WC, Caperna JC, Barber RE, et al. Incidence of and risk factors for clinically significant methicillin-resistant Staphylococcus aureus infection in a cohort of HIV-infected adults. J Acquir Immune Defic Syndr. 2005;40:155-160.
11. Senthilkumar A, Kumar S, Sheagren JN. Increased incidence of Staphylococcus aureus bacteremia in hospitalized patients with acquired immunodeficiency syndrome. Clin Infect Dis. 2001;33:1412-1416.
12. Kuehnert MJ, Kruszon-Moran D, Hill HA, et al. Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001-2002. J Infect Dis. 2006;193:172-179.
13. Graham PL III, Lin SX, Larson EL. A U.S. population-based survey of Staphylococcus aureus colonization. Ann Intern Med. 2006;144:318-325.
14. Kenner J, O'Connor T, Piantanida N, et al. Rates of carriage of methicillin-resistant and methicillin-susceptible Staphylococcus aureus in an outpatient population. Infect Control Hosp Epidemiol. 2003;24:439-444.
15. Jernigan JA, Pullen AL, Partin C, et al. Prevalence of and risk factors for colonization with methicillin-resistant Staphylococcus aureus in an outpatient clinic population. Infect Control Hosp Epidemiol. 2003;24:445-450.
16. Kluytmans J, van Belkum A, Verbrugh H. Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks. Clin Microbiol Rev. 1997;10:505-520.
17. Wertheim HF, Melles DC, Vos MC, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis. 2005;5:751-762.
18. Creech CB II, Kernodle DS, Alsentzer A, et al. Increasing rates of nasal carriage of methicillin-resistant Staphylococcus aureus in healthy children. Pediatr Infect Dis J. 2005;24:617-621.
19. Holbrook KA, Klein RS, Hartel D, et al. Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16:301-306.
20. McDonald LC, Lauderdale TL, Lo HJ, et al. Colonization of HIV-infected outpatients in Taiwan with methicillin-resistant and methicillin-susceptible Staphylococcus aureus. Int J STD AIDS. 2003;14:473-477.
21. Nguyen MH, Kauffman CA, Goodman RP, et al. Nasal carriage of and infection with Staphylococcus aureus in HIV-infected patients. Ann Intern Med. 1999;130:221-225.
22. Miller M, Cespedes C, Vavagiakis P, et al. Staphylococcus aureus colonization in a community sample of HIV-infected and HIV-uninfected drug users. Eur J Clin Microbiol Infect Dis. 2003;22:463-469.
23. Villacian JS, Barkham T, Earnest A, et al. Prevalence of and risk factors for nasal colonization with Staphylococcus aureus among human immunodeficiency virus-positive outpatients in Singapore. Infect Control Hosp Epidemiol. 2004;25:438-440.
24. Hidron AI, Kourbatova EV, Halvosa JS, 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;41:159-166.
25. Sissolak D, Geusau A, Heinze G, et al. Risk factors for nasal carriage of Staphylococcus aureus in infectious disease patients, including patients infected with HIV, and molecular typing of colonizing strains. Eur J Clin Microbiol Infect Dis. 2002;21:88-96.
26. Weinke T, Schiller R, Fehrenbach FJ, et al. Association between Staphylococcus aureus nasopharyngeal colonization and septicemia in patients infected with the human immunodeficiency virus. Eur J Clin Microbiol Infect Dis. 1992;11:985-989.
27. Miller M, Cespedes C, Bhat M, et al. Incidence and persistence of Staphylococcus aureus nasal colonization in a community sample of HIV-infected and -uninfected drug users. Clin Infect Dis. 2007;45:343-346.
28. Klein PA, Greene WH, Fuhrer J, et al. Prevalence of methicillin-resistant Staphylococcus aureus in outpatients with psoriasis, atopic dermatitis, or HIV infection. Arch Dermatol. 1997;133:1463-1465.
29. Chavez-Bueno S, Bozdogan B, Katz K, et al. Inducible clindamycin resistance and molecular epidemiologic trends of pediatric community-acquired methicillin-resistant Staphylococcus aureus in Dallas, Texas. Antimicrob Agents Chemother. 2005;49:2283-2288.
30. Oliveira DC, de Lencastre H. Multiplex PCR strategy for rapid identification of structural types and variants of the mec element in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2002;46:2155-2161.
31. Okuma K, Iwakawa K, Turnidge JD, et al. Dissemination of new methicillin-resistant Staphylococcus aureus clones in the community. J Clin Microbiol. 2002;40:4289-4294.
32. Pan ES, Diep BA, Charlebois ED, et al. Population dynamics of nasal strains of methicillin-resistant Staphylococcus aureus-and their relation to community-associated disease activity. J Infect Dis. 2005;192:811-818.
33. Skiest DJ, Brown K, Cooper T, et al. Prospective comparison of methicillin-susceptible and methicillin-resistant community associated Staphylococcus aureus infections in hospitalized patients. J Infect. 2007;54:427-434.
34. Cook HA, Furuya EY, Larson E, et al. Heterosexual transmission of community-associated methicillin-resistant Staphylococcus aureus. Clin Infect Dis. 2007;44:410-413.
35. Ellis MW, Hospenthal DR, Dooley DP, et al. Natural history of community-acquired methicillin-resistant Staphylococcus aureus colonization and infection in soldiers. Clin Infect Dis. 2004;39:971-979.
36. Lowy FD, Aiello AE, Bhat M, et al. Staphylococcus aureus colonization and infection in New York State prisons. J Infect Dis. 2007;196:911-918.
37. Begier EM, Frenette K, Barrett NL, et al. A high-morbidity outbreak of methicillin-resistant Staphylococcus aureus among players on a college football team, facilitated by cosmetic body shaving and turf burns. Clin Infect Dis. 2004;39:1446-1453.
38. Davis KA, Stewart JJ, Crouch HK, et al. Methicillin-resistant Staphylococcus aureus (MRSA) nares colonization at hospital admission and its effect on subsequent MRSA infection. Clin Infect Dis. 2004;39:776-782.
39. Mertz D, Frei R, Jaussi B, et al. Throat swabs are necessary to reliably detect carriers of Staphylococcus aureus. Clin Infect Dis. 2007;45:475-477.
40. Huang SS, Platt R. Risk of methicillin-resistant Staphylococcus aureus infection after previous infection or colonization. Clin Infect Dis. 2003;36:281-285.

MRSA; S. aureus; HIV; nasal colonization; community-associated MRSA; community-onset MRSA

© 2008 Lippincott Williams & Wilkins, Inc.