Cefepime-Enmetazobactam: A Drug Review of a Novel Beta-Lactam/Beta-Lactamase Inhibitor.

Objective: To describe and analyze the pharmacodynamic and pharmacokinetic properties and clinical evidence supporting the efficacy and use of cefepime-enmetazobactam (FEP-EMT).

Data sources: A literature search was conducted using MEDLINE and EMBASE databases (January 2015 to May 2024). Search terms included: "cefepime-enmetazobactam" or "cefepime" or "enmetazobactam" or "cefepime" or "novel beta-lactamase inhibitor" and "complicated urinary tract infection" or "cUTI." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review.

Study selection and data extraction: Relevant studies in English and clinical trials conducted in humans were reviewed.

Data synthesis: In February 2024, the Food and Drug Administration (FDA) approved the combination beta-lactam/beta-lactamase inhibitor (BL/BLI) FEP-EMT for the treatment of complicated urinary tract infections (cUTIs) and acute pyelonephritis following the completion of the Phase III ALLIUM trial comparing it to piperacillin-tazobactam (TZP). The trial resulted in 79.1% of the FEP-EMT group versus 58.9% of the TZP group meeting the primary outcome of clinical cure and microbiological eradication (95% CI 21.2 [14.3 to 27.9]).

Relevance to patient care and clinical practice in comparison to existing agents: This review describes the use of FEP-EMT for the treatment of cUTI and compares its use to other novel BL/BLI combinations including utility in drug-resistant infections.

Conclusions: FEP-EMT provides an antimicrobial option to reduce overuse of carbapenems for extended spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. However, unlike other novel BL/BLI combinations, its limited spectrum of antibacterial effect for more difficult-to-treat pathogens and cost may also impact its overall utilization.