San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
Christopher J. Graber, MD, MPH, is now with the Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, CA. Dr. Graber was supported by an HIV Translational Research Fellowship, University of California, San Francisco (5T32AI060530-02). No portions of this article have been published or presented elsewhere. All authors declare no competing financial interest.
To the Editor:
Skin and soft tissue infections (SSTI) caused by methicillin-resistant Staphylococcus aureus (MRSA) have been increasing in the United States with the emergence of the community-associated MRSA clone USA300 in 20001 and have become common in those infected with HIV.2,3 The USA300 genome contains a number of genetic factors that could potentially contribute to persistence and virulence of skin disease.4 Many factors could contribute to susceptibility to MRSA SSTI in HIV-infected persons, such as low CD4 count, absence of cotrimoxazole prophylaxis, sexual behaviors, and intravenous drug use. The convergence of these bacterial and host factors has resulted in high rates of MRSA SSTI recurrence.2,3
We sought to define the overall rate of and time to SSTI recurrence in patients presenting with an initial community-onset SSTI caused by MRSA in our HIV primary care clinic and to determine the relative association of MRSA genotype, clinical factors, behavioral factors, and antibiotic treatment with SSTI recurrence. Patients receiving care at the HIV primary care clinic at San Francisco General Hospital were retrospectively identified from an epidemiologic surveillance database of the Community Health Network of San Francisco that captures the first MRSA isolate per patient per year in the network from 1996 to 2007. A patient was eligible for inclusion in the study if he or she presented in the outpatient setting with a first episode of culture-proven MRSA SSTI from January 2002 through December 2006, had no history of a culture positive for MRSA at any site, and had at least 30 days of clinical follow-up after SSTI presentation. Clinical and demographic information at the time of initial presentation of MRSA SSTI was collected. The patients' medical record was then longitudinally reviewed through September 2007 for date of last follow-up or recurrence of SSTI (either culture positive for MRSA or clinically consistent with MRSA without a culture performed), site of recurrence, receipt of trimethoprim-sulfamethoxazole prophylaxis at any time during follow-up, and antibiotic susceptibility of MRSA isolates at disease recurrence (when available). A repeat SSTI at the same site as initial infection was only documented as recurrent if an interim progress note documented resolution of initial infection. Patients not seen by a clinical provider for more than a year were censored at the last visit before loss of follow-up. Methicillin-resistant Staphylococcus aureus isolates were classified as USA300 based on pulsed-field gel electrophoresis pattern, spa type 8, and the genes for Panton-Valentine leukocidin and the arginine catabolic mobile element as determined by polymerase chain reaction.4-7 Antimicrobial susceptibility testing was performed and interpreted in accordance with the Clinical and Laboratory Standards Institute guidelines. D testing was performed to test for inducible clindamycin resistance.
Of the 264 unique patients who received care at the San Francisco General Hospital HIV clinic and had culture-proven MRSA SSTI from January 2002 to December 2006, 34 were excluded because of a history of MRSA SSTI, 8 because of a history of MRSA isolated from a nonskin site, 134 because of a history of SSTI potentially consistent with MRSA, 20 because they had not established primary care at the clinic before presentation, and 6 because of inadequate follow-up. Thus, 62 patients were studied; their demographic, clinical, and microbiologic characteristics are shown in Table 1. It is of note that 87% of patients had an initial MRSA SSTI, which involved the USA300 clone encoding Panton-Valentine leukocidin and arginine catabolic mobile element. Compared with the general clinic population (as assessed in fiscal years 2006 and 2007), these patients tended to be somewhat younger (median age 39 vs. 45 years) and more likely to have CD4 <200 cells per milliliter (37.1% vs. 25.1%).
Forty-four (71.0%) patients experienced SSTI recurrence at a median of 135.5 days (range: 24-1116 days), with a median follow-up time of 190.5 days (range: 24-1495 days). Fifty percent of all patients had experienced SSTI recurrence by 281.5 days. Twelve (27.3%) patients had SSTI recurrence at the same site as the initial infection; no correlation was observed between anatomic site of initial infection and same-site SSTI recurrence. A culture yielded MRSA at the time of follow-up in 14 (31.8%) SSTI recurrences; no other pathogens were isolated. All these 14 recurrent isolates were susceptible to trimethoprim-sulfamethoxazole and rifampin. Five (35.7%) recurrent isolates were constitutively resistant to clindamycin, whereas 1 recurrent isolate displayed intermediate susceptibility to clindamycin. Two of the recurrent isolates were cultured from patients who had initial isolates resistant to clindamycin. Of the 3 isolates with acquired clindamycin resistance, only 1 was from a patient who received clindamycin for treatment of the initial infection. Of the 6 recurrent isolates on which tetracycline sensitivity was performed, 2 (33.3%) were resistant. Both these isolates also displayed clindamycin resistance; neither of the patients from which they were cultured received tetracyclines for treatment of their initial infection. Genotyping was available on 7 of the 14 recurrent isolates, all cultured from patients with USA300 as the initial infecting MRSA genotype. Six of these isolates were USA300, and 1 was not. Bivariate Cox regression performed on MRSA genotype and all patients' clinical and demographic factors with time to SSTI recurrence did not yield statistically significant results, nor did a multivariate Cox regression that accounted for the interaction between receipt of trimethoprim-sulfamethoxazole prophylaxis and CD4 <200 cells per milliliter (data not shown).
The results of this study demonstrate a remarkably high (71.0%) rate of SSTI recurrence in HIV-infected primary care patients presenting with initial community-onset SSTI caused by MRSA, with a median time to recurrence of approximately 4.5 months. Although small sample size and the retrospective nature of this study limit the conclusions we can draw and likely prevented us from making any association of SSTI recurrence with molecular, clinical, or demographic factors, it does seem clear that initial antibiotic susceptibility and antibiotics received for initial SSTI do not reliably predict antibiotic susceptibility in recurrent SSTI. This study complements another study from the same clinic that described a high prevalence of SSTI caused by multidrug-resistant USA300 MRSA that is particularly prevalent among men who have sex with men and is often isolated from the buttock/genitoperineal region.8 Taken together, these 2 studies suggest that reacquisition of MRSA infection via skin-to-skin contact with individuals infected or colonized with MRSA may play an important role in the pathogenesis of recurrent MRSA disease in patients infected with HIV. Thus, the HIV primary care practitioner faced with a patient presenting with an initial SSTI with a culture positive for MRSA can reasonably expect that the patient will more likely than not have a recurrence of SSTI. Routine culture with antibiotic susceptibility should be reperformed with each recurrence when possible. Efforts to reduce transmission and/or colonization should be considered, though the efficacy of MRSA decolonization in this setting remains unknown.
Christopher J. Graber, MD, MPH
Mark A. Jacobson, MD
Francoise Perdreau-Remington, PhD
Henry F. Chambers, MD
Binh An Diep, PhD
San Francisco General Hospital, University of California, San Francisco, San Francisco, CA
Christopher J. Graber is now with the Infectious Diseases Section, VA Greater Los Angeles Healthcare System, Los Angeles, CA.
Dr. Graber was supported by an HIV Translational Research Fellowship, University of California, San Francisco (5T32AI060530-02).
No portions of this article have been published or presented elsewhere.
All authors declare no competing financial interest.
1. Tenover FC, McDougal LK, Goering RV, et al. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus
widely disseminated in the United States. J Clin Microbiol
2. 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
3. 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
4. Diep BA, Gill SR, Chang RF, et al. Complete genome sequence of USA300, an epidemic clone of community-acquired meticillin-resistant Staphylococcus aureus. Lancet
5. McDougal LK, Steward CD, Killgore GE, et al. Pulsed-field gel electrophoresis typing of oxacillin-resistant Staphylococcus aureus
isolates from the United States: establishing a national database. J Clin Microbiol
6. Shopsin B, Gomez M, Montgomery SO, et al. Evaluation of protein A gene polymorphic region DNA sequencing for typing of Staphylococcus aureus
strains. J Clin Microbiol
7. Lina G, Piemont Y, Godail-Gamot F, et al. Involvement of Panton-Valentine leukocidin-producing Staphylococcus aureus
in primary skin infections and pneumonia. Clin Infect Dis
8. Diep BA, Chambers HF, Graber CJ, et al. Emergence of multi-drug resistant, community-associated methicillin-resistant Staphylococcus aureus
clone USA300 in men who have sex with men. Ann Intern Med