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

Abstract

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.

The Use of Noncarbapenem β-Lactams for the Treatment of Extended-Spectrum β-Lactamase Infections

“…Results of observational studies comparing the activity of cefepime and carbapenems for invasive ESBL infections have been conflicting with some studies showing no difference [39,40] and others suggesting cefepime therapy is inferior [38,41,42] (Table 4). Lee and colleagues conducted an observational study including 17 patients with ESBL bacteremia receiving cefepime therapy and 161 patients receiving carbapenem therapy [42].…”

“…Lee and colleagues conducted an observational study including 17 patients with ESBL bacteremia receiving cefepime therapy and 161 patients receiving carbapenem therapy [42]. Patients receiving carbapenems were over 7 times more likely to survive than patients receiving cefepime.…”

Clinical management of infections caused by multidrug-resistant Enterobacteriaceae

“…Such recommendations are controversial, and imply that an important proportion of ESBL producers, particularly isolates producing CTX-M enzymes, would be reported as susceptible to ceftazidime (and to a lesser extent to cefepime) [Rodriguez-Bañ o et al 2012c]. A recent retrospective cohort study found that cefepime (particularly when the MIC was 18 mg/liter) was independently associated with increased mortality among patients with bacteraemia due to ESBL-producing Enterobacteriaceae compared with carbapenems [Lee et al 2012]. In our opinion, there is still not enough information about the efficacy of active cephalosporins in the treatment of serious infections caused by ESBL producers, particularly for those from sources other than the urinary tract.…”

Klebsiella pneumoniae Carbapenemase-Producing Enterobacteriaceae Testing Susceptible to Cefepime by Reference Methods

“…Additionally, it has been reported recently that KPC-2 expression in Enterobacteriaceae is not enough to confer cefepime resistance (17). On the other hand, cefepime therapy of infections due to ESBL-producing Enterobacteriaceae was recently associated with lower survival rates among patients infected with isolates showing cefepime MICs of Ͼ1 g/ml, within the CLSI susceptibility range (18). Therefore, more studies in animal models, pharmacokinetic/ pharmacodynamic modeling, and/or focused clinical trials appear necessary to provide conclusive evidence that cefepime is a useful treatment option for infections due to KPC-producing isolates that demonstrate in vitro susceptibility to this agent under current CLSI breakpoints.…”