Outcomes Associated with Empiric Cefepime for Bloodstream Infections Caused by Ceftriaxone-Resistant, Cefepime-Susceptible Escherichia coli and Klebsiella pneumoniae

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International Journal of Antimicrobial Agents


BACKGROUND: Cefepime is a first-line agent for empiric sepsis therapy; however, cefepime use may be associated with increased mortality for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in a minimum inhibitory concentration (MIC)-dependent manner. The objective of this study was to compare the efficacy of empiric cefepime versus meropenem for bloodstream infections (BSI) caused by ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae with cefepime MICs ≤ 2 mg/L. METHODS: This single-center retrospective cohort study included patients admitted from October 2010 to August 2020 who received cefepime or meropenem empirically for sepsis with a blood culture growing ceftriaxone-resistant E. coli or K. pneumoniae. The primary outcome was 30-day mortality; secondary endpoints included 14-day mortality, recurrent BSI, readmission and recurrent infection within 90 days, time to clinical resolution of infection, time to clinical stability, and clinical stability at 48 hours. RESULTS: Fifty-four patients met inclusion criteria; 36 patients received meropenem, 18 received cefepime. The median (IQR) treatment duration of cefepime and meropenem were 3 (2-6) and 7 (5-10) days, respectively. Thirty-day and 14-day mortality were similar between cefepime and meropenem (11.1% vs 2.8%; p = 0.255, and 5.6 % vs 2.8%; p = 1.00, respectively); cefepime was associated with longer time to clinical stability compared to meropenem (median: 38.48 hours vs 21.26; p = 0.016). CONCLUSION: Mortality was similar between groups, although most patients receiving cefepime did not complete therapy with cefepime. Empiric cefepime was associated with a delay in achieving clinical stability when compared to meropenem to treat BSI caused by ceftriaxone-resistant Enterobacterales, even when cefepime-susceptible.

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