title: Determining a clinical framework for use of cefepime and β-lactam/β-lactamase inhibitors in the treatment of infections caused by extended-spectrum-β-lactamase-producing Enterobacteriaceae.
abstract: Traditionally, physicians have not used cefepime (a fourth-generation cephalosporin with greater stability against β-lactamases) or β-lactam/β-lactamase inhibitors (BLBLIs) for infections caused by bacteria (generally Escherichia coli and Klebsiella species) that produce an extended-spectrum β-lactamase (ESBL). Many microbiology laboratories have historically labelled these ESBL-producing organisms as resistant to all cephalosporins regardless of their MIC. The recommendation to eliminate ESBL identification started with EUCAST in 2009, followed by CLSI in 2010. As a consequence, many ESBL-producing organisms that were previously labelled as resistant to all cephalosporins may be reclassified as susceptible to some (particularly cefepime), depending on their MICs. Because there are limited treatment options against ESBL-producing organisms, there is growing interest in using cefepime and BLBLIs. In this review, we examine the clinical outcomes of therapy directed against ESBL-producing Enterobacteriaceae and the pharmacokinetics/pharmacodynamics of cefepime and BLBLIs to construct a clinical framework for how physicians can best employ these carbapenem-sparing alternatives for the treatment of infections caused by ESBL-producing Enterobacteriaceae. We conclude that standard-dose cefepime is a reasonable option for the definitive therapy of invasive infections resulting from ESBL-producing E. coli and Klebsiella species when the MIC for the organism is ≤ 2 mg/L (CLSI) or ≤ 1 mg/L (EUCAST), although higher doses may be considered for MICs in the 4-8 mg/L range. Piperacillin/tazobactam is also a reasonable option when the MIC is ≤ 16 mg/L.
authors.affiliation: Northwest Permanente, Portland, OR, USA.
authors.forename: Hien M
authors.initials: HM
authors.lastname: Nguyen
authors.forename: Kileen L
authors.initials: KL
authors.lastname: Shier
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Graber
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D000077723:Cefepime; D002511:Cephalosporins / Q000627:therapeutic use*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000201:enzymology; D004756:Enterobacteriaceae Infections / Q000188:drug therapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016896:Treatment Outcome; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D000077723:Cefepime; D001618:beta-Lactamases
keywords: ESBLs; antimicrobial resistance; pharmacokinetics/pharmacodynamics; piperacillin/tazobactam