Multidrug-Resistant CA-MRSA Infections Among HIV+ Persons

Loren Gregory Miller, LA Biomedical Research Institute at Harbor-UCLA Medical
Basic-Applied Clinical

An emerging problem affecting HIV-infected persons is community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections. CA-MRSA infections usually manifest as skin and soft tissue infections (SSTI's) and typically require both antibiotic therapy and surgical drainage. CA-MRSA infections lead to considerable morbidity, hospitalization, surgery, and occasionally death. There are ample data demonstrating that the incidence of CA-MRSA infection is high among HIV-infected persons, especially among HIV-infected men who have sex with men (MSM) and HIV-infected drug users.

Most CA-MRSA infections are caused by a single clone of MRSA, designated USA300. Of great concern is that a subclone of USA300 containing the multiresistance conjugative plasmid pUSA03 have emerged in the community as a cause of SSTI. Data from our group demonstrated that a rapid rise in the incidence of pUSA03 MRSA subclone infections and that this subclone almost exclusively infects HIV- infected persons and MSM. The pUSA03 subclone is resistant to almost all oral antibiotics used to treat skin and MRSA infections (including beta-lactams, clindamycin, tetracycline, fluoroquinolones, macrolides, and mupirocin). There is an urgent need for descriptive and epidemiologic data examining the spread of this subclone among HIV-infected persons.

The specific aims of our investigation are:

  1. To describe the molecular epidemiology of CA-MRSA infections among HIV-infected persons with CA-MRSA infection. Data from this application will complement California Collaborative Treatment Group (CCTG) Study 587, which will be conducted at 5 clinical sites in California. CCTG 587 is a prospective case- control study of patients with and without acute CA-MRSA infection This epidemiologic investigation will collect rich data on high-risk sexual and drug use behaviors, given there is little known about what specific behaviors put MSM and drug users at high risk for MRSA infection. The present application will add molecular epidemiology of the infecting MRSA and S. aureus strains isolated from case-patients in CCTG 587. Specifically, it will support: 1) multilocus sequence typing (MLST) and spa strain typing of S. aureus strains, and 2) identification of the molecular genetic basis of multidrug resistance. Special emphasis will be made to identify the pUSA03 MRSA subclone, and describe its prevalence as a pathogen.
  2. To describe the molecular epidemiology and burden of colonization of antibiotic-resistant S. aureus strains (such as the pUSA03 MRSA subclone) among HIV-infected persons with and without CA-MRSA infection.
  3. To determine risk factors for developing infection with the pUSA03 MRSA subclone among HIV- infected patients. We hypothesize that there are specific high risk sexual and drug use behaviors that major risks for a pUSA03 MRSA subclone infection.

Findings from our investigation will be critical for quantifying the rise of the highly concerning pUSA03 MRSA subclone in California. This descriptive investigation will provide crucial information to establish guidelines for empirical antibiotic therapy for skin infections. Furthermore, our epidemiologic investigations of colonization and risk factors for the pUSA03 MRSA subclone will provide important insights into the development of multidrug resistance in CA-MRSA. This information will be crucial for developing future interventions to prevent spread of this serious and suddenly common infection.