Cefepime Therapy for Monomicrobial Bacteremia Caused by Cefepime-Susceptible Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae: MIC Matters

Abstract

Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae isolates are important clinical pathogens. In addition, the efficacy of cefepime for such infections is controversial. We performed a retrospective study of monomicrobial bacteremia caused by ESBL producers at 2 medical centers between May 2002 and August 2007. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) in a propensity score-matched analysis to assess therapeutic effectiveness. The 30-day crude mortality is the primary endpoint. A total of 178 patients were eligible for the study. Patients who received cefepime (n = 17) as definitive therapy were more likely to have a clinical failure (odds ratio [OR] 6.2; 95% confidence interval [CI], 1.7-22.5; P = .002), microbiological failure (OR 5.5; 95% CI, 1.3-25.6; P = .04), and 30-day mortality (OR 7.1; 95% CI, 2.5-20.3; P < .001) than those who received carbapenem therapy (n = 161). Multivariate regression revealed that a critical illness with a Pitt bacteremia score ≥ 4 points (OR 5.4; 95% CI, 1.4-20.9; P = .016), a rapidly fatal underlying disease (OR 4.4; 95% CI, 1.5-12.6; P = .006), and definitive cefepime therapy (OR 9.9; 95% CI, 2.8-31.9; P < .001) were independently associated with 30-day crude mortality. There were 17 case-control pairs in the propensity scores matched analysis. The survival analysis consistently found that individuals who received cefepime therapy had a lower survival rate (log-rank test, P = .016). Based on the current Clinical and Laboratory Standards Institute susceptible breakpoint of cefepime (minimum inhibitory concentration ≤ 8 μg/mL), cefepime definitive therapy is inferior to carbapenem therapy in treating patients with so-called cefepime-susceptible ESBL-producer bacteremia.