POSITIONING CEFEPIME–ENMETAZOBACTAM AGAINST THE LAST RESTORE ANTIBIOTIC

Abstract
Objective:
To assess the antimicrobial potential of cefepime–enmetazobactam, an emerging β-lactam/β-
lactamase inhibitor (BL/BLI) combination, against multidrug-resistant Gram-negative pathogens,
particularly carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa.
Methods:
Cefepime–enmetazobactam efficacy, resistance mechanisms, pharmacokinetic/pharmacodynamic
(PK/PD) concerns, and safety results were assessed by reviewing recent in vitro investigations,
clinical assessments, and comparative registry analyses.
Results:
Cefepime–enmetazobactam showed promising but selective action against subsets of CRE,
especially class A β-lactamases like klebsiella pneumoniae carbapenemase (KPC). The activity was
restricted against class B metallo-β-lactamases, such as New Delhi metallo-β-lactamase (NDM) and
Verona Integron-encoded Metallo-β-lactamase (VIM). Clinical studies showed it works well in
treating complicated urinary tract infections (cUTI), bloodstream infections, and hospital-acquired
pneumonia, with outcomes better or comparable to standard therapies. Importantly, its safety profile
was similar to other β-lactam antibiotics, with no new major side effects reported.
Conclusion:
Cefepime–enmetazobactam represents a promising addition to the antimicrobial armamentarium,
particularly effective against ESBL- and KPC-producing Enterobacterales, making it a strong
carbapenem-sparing alternative in cUTI, bacteremia, and HAP/VAP.