The Impact of Concomitant Empiric Cefepime on Patient Outcomes of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections Treated With Vancomycin

BACKGROUND: Data suggest that vancomycin + β-lactam combinations improve clearance of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs). However, it is unclear which specific β-lactams confer benefit. This analysis evaluates the impact of concomitant empiric cefepime on outcomes of MRSA BSIs treated with vancomycin. METHODS: Retrospective cohort study of adults with MRSA BSI from 2006 to 2017. Vancomycin + cefepime therapy was defined as ≥24 hours of cefepime during the first 72 hours of vancomycin. The primary outcome was microbiologic failure, defined as BSI duration ≥7 days and/or 60-day recurrence. Multivariable logistic regression was used to evaluate the association between vancomycin + cefepime therapy and binary outcomes. Cause-specific and subdistribution hazard models were used to evaluate the association between vancomycin + cefepime and BSI clearance. RESULTS: Three hundred fifty-eight patients were included, 129 vancomycin and 229 vancomycin + cefepime. Vancomycin + cefepime therapy was independently associated with reduced microbiologic failure (adjusted odds ratio [aOR], 0.488; 95% confidence interval [CI], 0.271–0.741). This was driven by a reduction in the incidence of BSI durations ≥7 days (vancomycin + cefepime aOR, 0.354; 95% CI, 0.202–0.621). Vancomycin + cefepime had no association with 30-day mortality (aOR, 0.952; 95% CI, 0.435–2.425). Vancomycin + cefepime was associated with faster BSI clearance in both cause-specific (HR, 1.408; 95% CI, 1.125–1.762) and subdistribution hazard models (HR, 1.264; 95% CI, 1.040–1.536). CONCLUSIONS: Concomitant empiric cefepime improved MRSA BSI clearance and may be useful as the β-lactam component of synergistic vancomycin + β-lactam regimens when empiric or directed gram-negative coverage is desired.