Cefepime 2.0: Upgrading β-Lactamase Inhibitor Use

Antimicrobial resistance (AMR) in Gram-negative pathogens represents a critical global health challenge. Combining cefepime with novel β-lactamase inhibitors (enmetazobactam, taniborbactam, zidebactam, and nacubactam) revitalizes the role of this fourth-generation cephalosporin in contemporary therapy. We present a narrative review according to the Scale for the Assessment of Narrative Review Articles (SANRA) criteria, summarizing the existing literature regarding new cefepime combinations with β-lactamase inhibitors. Based on 68 identified studies, data were structured by molecule. Each section explores in vitro activity, preclinical in vivo data, PK/PD parameters, clinical evidence, and dosage. Findings demonstrate that these inhibitors successfully restore cefepime’s efficacy against diverse resistance mechanisms, notably ESBLs, AmpC, KPC, OXA-48, and metallo-β-lactamases. “Cefepime 2.0” therapies expand the therapeutic armamentarium against severe multidrug-resistant infections, offering vital carbapenem-sparing strategies. Because they possess distinct microbiological spectra, these agents serve complementary rather than interchangeable roles. Their clinical success demands targeted integration into antimicrobial stewardship programs to optimize efficacy and safely reduce carbapenem dependence.