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

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.

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.

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.