Novel beta-lactamase inhibitors with cefepime: where do they fit in clinical practice?

Introduction: Enmetazobactam, taniborbactam, and zidebactam are novel β-lactamase inhibitors that have been combined with cefepime in an effort to overcome common and emerging mechanisms of antimicrobial resistance.

Areas covered: We performed a literature review of articles written in English using MEDLINE, PUBMED, and EMBASE, using the search terms 'Cefepime-enmetazobactam,' 'cefepime-taniborbactam,' and 'Cefepime-zidebactam' between January 2015 and May 2025. This review summarizes the in vitro, animal, and clinical data for cefepime-enmetazobactam, cefepime-taniborbactam, and cefepime-zidebactam to forecast their potential role in clinical practice.

Expert opinion: Cefepime-enmetazobactam and cefepime-taniborbactam are among the newest additions to an expanding antibiotic armamentarium; however, their precise role in clinical practice remains to be defined given that their in vitro activity overlaps with current treatment options. On balance, the in vitro activity of cefepime-zidebactam fills critical gaps for the most challenging Gram-negative pathogens, including those that harbor metallo-β-lactamases with or without mutations in penicillin-binding proteins. For each of these agents, clinical data and real-world evidence generation are needed to better define their therapeutic niche, potential for resistance selection, and potential benefits compared to currently available antibiotics.