Cefepime/Enmetazobactam: a microbiological, pharmacokinetic, pharmacodynamic and clinical evaluation

Expert Opin Drug Metab Toxicol. 2024 Nov 7. doi: 10.1080/17425255.2024.2427310. Online ahead of print.

Abstract

Introduction: Cefepime/enmetazobactam is a novel β-lactam/β-lactamase inhibitor (BL-BLI) combination with broad Gram-positive and -negative activity. Cefepime is relatively resistant to hydrolysis by AmpC and enmetazobactam inhibits all Ambler Class A extended spectrum β-lactamases (ESBLs). Hence the combination is resistant to hydrolysis by many ESBLs. Important spectrum gaps are MRSA, enterococci, Acinetobacter spp. and anaerobes. There is no completely reliable activity against carbapenem resistant organisms.

Areas covered: We describe the chemistry, pharmacodynamics, pharmacokinetics, toxicities, drug-drug interactions, clinical efficacy and current regulatory position of cefepime/enmetazobactam, following a review of available published literature relating to cefepime/enmetazobactam.

Expert opinion: The main potential role for cefepime/enmetazobactam is as a carbapenem-sparing agent for the treatment of infections caused by ESBL-producing Enterobacterales to prevent the use of carbapenems and to avoid the toxicities of non-β-lactam alternatives.There may be potential uses for cefepime/enmetazobactam for the treatment of reproductive tract infections, abdominal infections and neonatal sepsis, given the spectrum of activity and pharmacokinetic properties. However, additional non-clinical and clinical studies are required before use in these settings.

Keywords: Cefepime; ESBL; Pharmacodynamics; Pharmacokinetics; enmetazobactam; urinary tract infection; β-lactam; β-lactam/β-lactamase inhibitor combination; β-lactamase inhibitor.

Publication types

  • Review