Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with increased health care costs, morbidity, and mortality as well as worse treatment outcomes than methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia (1, 2). Moreover, a recent study found that 88% of invasive, nosocomial MRSA infections involved a positive blood culture (3). Vancomycin (VAN) has been the mainstay of MRSA treatment for over 40 years, but concerns regarding the efficacy of VAN against MRSA are mounting (4). VAN has been shown to have slow bactericidal activity, poor antistaphylococcal activity, poor tissue penetration, and high rates of infection relapse (1,(5)(6)(7)(8)(9)(10).Given the widespread use of VAN for treating MRSA infections despite its questionable efficacy, several in vitro studies have explored combination therapy using VAN with a ␤-lactam (BL) against MRSA. An in vitro pharmacokinetic/pharmacodynamic (PK/PD) model simulating in vivo antibiotic exposure demonstrated that VAN in combination with cefazolin improved antibacterial activity against MRSA and heterogeneous vancomycin intermediate-susceptible Staphylococcus aureus (hVISA) isolates compared to VAN alone (11). Another in vitro pharmacokinetic/ pharmacodynamic model by Leonard demonstrated increased bactericidal activity against MRSA and hVISA using a combination of VAN and nafcillin compared to VAN alone (12). Piperacillin-tazobactam in combination with VAN has also demonstrated synergistic activity against MRSA and VISA isolates in time-kill studies (13,14).BLs are often empirically added to VAN as Gram-negative coverage for many disease states, including pneumonia and septic shock (15, 16). However, despite extensive clinical use of these regimens, little is known about the impact of BLs on VAN activity against MRSA. While in vitro studies have demonstrated synergy between BLs and VAN against MRSA isolates, studies looking at clinical outcomes of these combinations have not been performed. The objective of this study was to examine the impact of combination therapy with VAN and a ␤-lactam for Ն24 h on the microbiological eradication of MRSA bacteremia compared to VAN alone. MATERIALS AND METHODSStudy design, setting, and population. A retrospective cohort study was conducted at the University of New Mexico Hospital (UNMH), a 646-bed tertiary care academic medical center in Albuquerque, NM. This study was approved by the University of New Mexico Human Research Review Committee. This study conforms to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations for reporting cohort studies (17). Patients were eligible for study inclusion if they met the following criteria: (i) they were admitted to UNMH between January 2005 and December 2012; (ii) they were Ն18 years of age at the time of admission; (iii) they had had at least one blood culture positive for MRSA with a VAN MIC of Յ2 mg/liter by the BD Phoenix or Vitek automated microbiological system, and the isolate was available for further microbi...

High failure rates were observed in patients with MRSA bacteraemia treated with vancomycin, despite high vancomycin troughs and low rates of nephrotoxicity. Predictors of vancomycin failure included endocarditis and pneumonia. In these situations, vancomycin provides suboptimal therapy.

Vancomycin with piperacillin-tazobactam is used as empirical therapy for critically ill patients. Studies of this combination against methicillin-resistant

This work was supported in part by a research grant to Dilworth, Mercier, and Borrego from the American Society of Health-System Pharmacists Foundation. Klein and Pinkerton were supported in part by grants T32-MH19985 and P30-MH52776, respectively, from the National Institute of Mental Health. No funding bodies had any role in the study design, data collection, analysis, decision to publish, or preparation of the manuscript. The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the Health Resources and Services Administration. The authors have no conflicts of interest to disclose. Study concept and design were contributed primarily by Dilworth, Mercier, and Borrego, along with the other authors. Dilworth took the lead in data collection, along with Pinkerton, Klein, Mercier, and Jakeman. Data interpretation was performed by Dilworth and Pinkerton, along with the other authors. The manuscript was written by Dilworth, Klein, and Jakeman, with assistance from the other authors, and revised by Dilworth, Jakeman, and Klein, with assistance from the other authors. The results from this study were presented in part at the 2015 United States Conference on AIDS in Washington, DC, on September 10-13, 2015.

The in vivo efficacy of LY333328, a new glycopeptide antibiotic, was compared with that of vancomycin by using the rabbit model of left-sided methicillin-resistant Staphylococcus aureusendocarditis. Animals received LY333328 or vancomycin (25 mg/kg of body weight every 24 or 8 h, respectively) for 4 days. These drugs were equally effective in clearing bacteremia and in reducing bacterial counts in vegetations and tissues. We conclude that in this model, LY333328 was microbiologically effective and may be a therapeutic alternative to vancomycin.