OBJECTIVE Staphylococcus aureus is a cause of community- and healthcare-acquired infections and is associated with substantial morbidity, mortality, and costs. Vancomycin minimum inhibitory concentrations (MICs) among S. aureus have increased, and reduced vancomycin susceptibility (RVS) may be associated with treatment failure. We aimed to identify clinical risk factors for RVS in S. aureus bacteremia. DESIGN Case-control. SETTING Academic tertiary care medical center and affiliated urban community hospital. PATIENTS Cases were patients with RVS S. aureus isolates (defined as vancomycin E-test MIC >1.0 μg/mL). Controls were patients with non-RVS S. aureus isolates. RESULTS Of 392 subjects, 134 (34.2%) had RVS. Fifty-eight of 202 patients (28.7%) with methicillin-susceptible S. aureus (MSSA) isolates had RVS, and 76 of 190 patients (40.0%) with methicillin-resistant S. aureus (MRSA) isolates had RVS (P =.02). In unadjusted analyses, prior vancomycin use was associated with RVS (odds ratio [OR], 2.08; 95% confidence interval [CI], 1.00–4.32; P =.046). In stratified analyses, there was significant effect modification by methicillin susceptibility on the association between vancomycin use and RVS (P = .04). In multivariable analyses, after hospital of admission and prior levofloxacin use were controlled for, the association between vancomycin use and RVS was significant for patients with MSSA infection (adjusted OR, 4.02; 95% CI, 1.11–14.50) but not MRSA infection (adjusted OR, 0.87; 95% CI, 0.36–2.13). CONCLUSIONS A substantial proportion of patients with S. aureus bacteremia had RVS. The association between prior vancomycin use and RVS was significant for patients with MSSA infection but not MRSA infection, suggesting a complex relationship between the clinical and molecular epidemiology of RVS in S. aureus.

bReduced vancomycin susceptibility (RVS) may lead to poor clinical outcomes in Staphylococcus aureus bacteremia. The objective of this study was to evaluate the clinical and economic impact of RVS in patients with bacteremia due to S. aureus. A cohort study of patients who were hospitalized from December 2007 to May 2009 with S. aureus bacteremia was conducted within a university health system. Multivariable logistic regression and zero-truncated negative binomial regression models were developed to evaluate the association of RVS with 30-day in-hospital mortality, length of stay, and hospital charges. One hundred thirty-four (34.2%) of a total of 392 patients had bacteremia due to S. aureus with RVS as defined by a vancomycin Etest MIC of >1.0 g/ml. Staphylococcus aureus is a leading cause of nosocomial and community-acquired infections worldwide (15,20) and is associated with increased mortality, length of hospital stay, and total health care expenditures (7). Vancomycin has long been considered the mainstay of therapy for infections due to methicillin-resistant S. aureus (MRSA) as well as infections due to methicillin-susceptible S. aureus (MSSA) in patients with intolerance to beta-lactam antibiotics. However, a recently recognized phenomenon of increasing vancomycin MICs over time has been described among vancomycin-susceptible S. aureus isolates, referred to as vancomycin "MIC creep" (13,37,40).Several studies suggest that reduced vancomycin susceptibility (RVS), even with vancomycin MICs in the susceptible range, is associated with higher rates of treatment failure and mortality, particularly in bloodstream infections due to MRSA (2,14,17,21,26,28,29,31,33,36,42,44). However, these studies have been limited by small sample sizes (2,14,26,28,29,31,33,42,44), methodological issues with the selection of patients and study endpoints (2,14,28,29,33,36), and evaluation of potential confounders (29,36,42). Furthermore, there are very few reports evaluating the association between RVS and clinical outcomes in infections due to MSSA instead of MRSA (2, 17, 31). These studies have similarly been limited by small sample sizes (2, 31) and incomplete ascertainment of potential confounders (17,31).Given these issues, it is critical to elucidate the clinical impact of RVS in both MRSA and MSSA infections in order to identify optimal treatment strategies and reduce associated mortality. We conducted this cohort study to determine the association between RVS and mortality in S. aureus bacteremia. Furthermore, to our knowledge, our study is the first to investigate the relationship between RVS and length of stay (LOS) and total hospital charges in patients with S. aureus bacteremia. MATERIALS AND METHODSStudy design and setting. This retrospective cohort study was conducted at two hospitals in the University of Pennsylvania Health System (UPHS) in Philadelphia, PA: the Hospital of the University of Pennsylvania (HUP), a 725-bed academic tertiary care medical center, and Penn Presbyterian Medical Center (PPMC), a 344-bed u...

Among pediatric and adult providers, 70% preferred trimethoprim-sulfamethoxazole for directed treatment of community-associated methicillin-resistant Staphylcoccus aureus skin and soft-tissue infections, although a higher proportion of pediatric compared to adult providers favored clindamycin (36% vs. 8%, p<0.0001). For recurrent infections, 88% of providers employed at least one topical decolonization strategy.