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Risk Factors and Outcomes of Infections Due to USA300 Methicillin-Resistant Staphylococcus aureusBackground: The epidemiology of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) bacteremia is unknown. We evaluated outcomes of and risk factors for USA300 MRSA bacteremia, and assessed infection control rules identifying CA-MRSA infections. Objective: The objectives were: 1) to determine if mortality was greater in patients with USA300 MRSA bacteremia vs. A) non-USA300 MRSA bacteremia or B) uninfected controls; 2) to evaluate if illicit drug users developed USA300 MRSA bacteremia more vs. A) all other S. aureus bacteremia or B) no infection; and 3) to validate the 48-hour rule identifying CA-MRSA infections. Methods: The population included veterans at the VAMC in: 1) Baltimore, MD, 2) Washington, DC, 3) Buffalo, NY, and 4) Richmond, VA. A cohort study was used for objectives 1A, 1B, and 2A, a matched case-control study for objective 2B, and a validation study for objective 3. All isolates were molecularly classified as USA300 MRSA or other. Results: Patients with USA300 MRSA bacteremia were less likely to die within 90 days than patients with non-USA300 MRSA bacteremia, though not statistically significant (adjusted Relative Risk [aRR]=0.8; 95% Confidence Interval [CI]: 0.5-1.2), and more likely to die within 30 days than uninfected patients (adjusted OR [aOR]: 3.6; 95% CI: 1.1-11.6). The association of illicit drug use and USA300 MRSA bacteremia decreased over the study period (aRR for early years=4.6; 95% CI 2.2, 8.9; aRR for late years=2.5; 95% CI 1.2, 4.2). USA300 MRSA bacteremic subjects were more often illicit drug users than uninfected patients (aOR: 2.2; 95% CI: 0.8, 6.2). The 48-hour rule had 100% sensitivity and 38% specificity for identifying CA-MRSA infections. Most patients (89%) diagnosed with a CA-MRSA infection by this rule had recent healthcare contact. Conclusions: In patients with MRSA bacteremia, USA300 MRSA may not be more virulent than other MRSA strains. Illicit drug users are more likely to have bacteremia due to USA300 MRSA than all other types of S. aureus or no infection. Most patients identified as CA-MRSA by surveillance rules had recent healthcare contact. This suggests that infection control efforts in hospitals could limit the spread of the USA300 MRSA strain in both hospitals and the community.