INTRODUCTION: The global rise of multidrug-resistant (MDR) Gram-negative pathogens challenges therapy, driving development of novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations. Cefepime-based combinations offer mechanistically diverse options against a broad range of resistance phenotypes. AREAS COVERED: This review summarizes approved and investigational cefepime-based BL/BLI combinations, including cefepime/enmetazobactam (FEP/EMT), cefepime/taniborbactam (FTB), cefepime/zidebactam (FPZ), and cefepime/nacubactam (FEP/NAC). We discuss microbiological activity, resistance mechanisms, pharmacokinetics/pharmacodynamics, and available clinical evidence. In vitro data show differential activity against ESBL-, AmpC-, and carbapenemase-producing Enterobacterales, as well as difficult-to-treat Pseudomonas aeruginosa, with emerging but limited clinical outcomes. Challenges include incomplete resistance coverage, geographic variability, and limited clinical trials. EXPERT OPINION: Cefepime-based BL/BLI therapy should be pathogen- and mechanism-driven. FEP/EMT is suited for ESBL- and AmpC-producing Enterobacterales, potentially sparing carbapenems and covering OXA producers if susceptible. FTB may target severe carbapenem-resistant Enterobacterales infections resistant to existing BL/BLI agents, considering coverage for metallo-β-lactamases (MBL). FPZ combines β-lactamase inhibition and β-lactam - enhancer activity, retaining activity against XDR Enterobacterales and P. aeruginosa, including cefiderocol- or aztreonam/avibactam (ATM/AVI)-resistant strains. FEP/NAC shows promise against carbapenem- and MBL-producing strains, though clinical data remain limited. Optimal use relies on rapid molecular diagnostics, susceptibility testing, and antimicrobial stewardship to maximize efficacy and limit the emergence of resistance.
Pipitò et al. (Tue,) studied this question.