Cefepime-enmetazobactam for complicated urinary tract infections: Redefining ESBL therapy

Complicated urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)- and AmpC β-lactamase-producing Enterobacterales are increasing in India, driving carbapenem use. Cefepime-enmetazobactam (CPM-EMT), a β-lactamase inhibitor active against class A ESBLs and with partial activity against AmpC, but is inactive against metallo-β-lactamases (MBLs). We conducted a narrative review (2018-2025) of PubMed/MEDLINE, ClinicalTrials.gov, and regulatory sources, prioritising randomised trials, surveillance, pharmacokinetic/pharmacodynamic studies, and antimicrobial stewardship programme (AMSP) guidance, with emphasis on Indian resistance trends. In the Phase 3 ALLIUM trial, CPM-EMT achieved superior overall treatment success versus piperacillin-tazobactam in patients with complicated UTI and acute pyelonephritis, including ESBL subgroups. In vitro, CPM-EMT restores cefepime activity against ESBL-producing Enterobacterales; activity against Pseudomonas aeruginosa is variable and largely cefepime-driven. Safety is similar to cefepime; the risk of neurotoxicity increases with renal impairment, supporting renal dose adjustment and prolonged infusion in augmented renal clearance. CPM-EMT is approved in the United States, European Union, and India. CPM-EMT is a carbapenem-sparing option for ESBL/AmpC complicated UTI when MBL risk is low or excluded by rapid carbapenemase testing and local epidemiology. It is not appropriate for empiric use in haemodynamically unstable ICU patients or where carbapenemase prevalence (e.g., NDM-β-lactamase, OXA-48-like, KPC) is high; mechanism-directed alternatives (e.g., ceftazidime-avibactam with or without aztreonam, cefiderocol) are preferred. Evidence gaps include paediatric dosing/safety, Indian real-world comparative outcomes, Pseudomonas-specific efficacy, and cost-effectiveness. Implementation in India should integrate rapid diagnostics, local antibiograms, and optimised dosing within AMSP pathways to preserve carbapenems without compromising outcomes.