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

Abstract

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.

Monotherapy with Vancomycin or Daptomycin versus Combination Therapy with β-Lactams in the Treatment of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections: A Retrospective Cohort Analysis

“…To our knowledge, this is the largest realworld study to date comparing clinical outcomes in MRSA BSI patients receiving VAN/DAP MT to VAN/DAP CT with BL. Strengths of this study include a specific definition of BL exposure with regards to VAN/DAP timing, exclusion of patients who have not had a follow-up blood culture, robust sample size captured in over 12 years duration, and findings that are confirmatory of previously published data in CT for MRSA BSI [8,25,26].…”

“…Notably, CT patients had a higher APACHE II score, intensive care unit (ICU) encounter, were more likely to be admitted from nursing facilities and had BSI sources commonly associated with high mortality (i.e., pneumonia/LRT and infective endocarditis). This further complicates the conflicting evidence in regard to survival benefits with BL combination therapy particularly with rapid bacterial eradication [8,9,16,25,37,38].…”

“…Prior Presentation. This study has been presented, in part, at American Society for Microbiology (ASM); October 3 -7, 2018 San Francisco, CA (abstract 2379) and the following publications Zasowski et al and Jorgensen et al [25,26].…”

Adjuvant β-Lactam Therapy Combined with Vancomycin or Daptomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: a Systematic Review and Meta-analysis

“…After applying the inclusion/exclusion criteria, a total of 15 studies ( 6 , 18 – 31 ) comprising a total of 2,594 patients were included (1,189 patients in the standard therapy [STAN] group and 1,405 patients in the STAN therapy combined with β-lactams [COMBO] group), including 7 studies ( 21 – 27 ) based on the combination of VAN, 5 studies ( 6 , 28 – 31 ) based on the combination of DAP, and 3 studies ( 18 – 20 ) based on the combination of daptomycin or vancomycin. Among the included studies, the β-lactam of choice was ceftaroline in four studies ( 20 , 29 – 31 ), cefazolin in three studies ( 19 , 23 , 25 ), flucloxacillin in two studies ( 19 , 22 ), cloxacillin in one study ( 19 ), and cefepime in one study ( 27 ). In six cohort studies, β-lactams generally comprised more than 3 antibacterial agents ( 18 , 21 , 26 , 28 ) or unknown varieties ( 6 , 24 ).…”

“…The quality of the 12 included cohort studies was evaluated using the Newcastle-Ottawa scale (NOS). There were a total of seven studies with NOS scores of ≥6 points, of which three scored 7 points ( 18 , 26 , 28 ) and four scored 6 points ( 20 , 21 , 27 , 31 ). Studies published in the abstract form all scored <6 points, of which three ( 23 – 25 ) scored 3 points and one ( 29 ) scored 4 points.…”