Combination of Vancomycin or Daptomycin and Beta-lactam Antibiotics: A Meta-analysis

INTRODUCTION Observational and randomized controlled trials of the combination of vancomycin or daptomycin with a beta-lactam (BL) in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia have shown conflicting results on patient outcomes. OBJECTIVES The primary purpose of this meta-analysis was to compare clinical failure with the combination of vancomycin or daptomycin with a BL versus vancomycin or daptomycin monotherapy in MRSA bacteremia or endocarditis. METHODS A systematic literature search of PubMed, Embase, CINAHL, and meeting proceedings was conducted from inception through February 11, 2020, to identify relevant studies. The primary outcome was clinical failure and secondary outcomes were mortality, nephrotoxicity, and bacteremia. The meta-analysis was performed using Comprehensive Meta Analysis (version 3.0) with a random effects model. Outcomes were reported as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS Nine studies of 1636 patients receiving vancomycin or daptomycin monotherapy versus the combination of vancomycin or daptomycin plus BL for MRSA bacteremia were included. Results showed combination therapy was associated with significantly lower clinical failure rates (OR 0.56, 95% CI 0.39-0.79, I-2 = 26.22%, p=0.001). Improvement in clinical failure was driven by lower rates of bacteremia relapse and persistence. However, no difference was seen with mortality. CONCLUSIONS Combination therapy with vancomycin or daptomycin plus BL for MRSA bacteremia showed lower clinical failure rates, however, no significant difference was seen in mortality.