Cefepime-Taniborbactam-a Novel Combination Therapy for Multidrug-Resistant Pathogens

The ongoing spread of antimicrobial resistance has generated an urgent need for new antibiotics, especially against multidrug-resistant (MDR) gram-negative pathogens. Taniborbactam (previously VNRX-5133) is a novel bicyclic boronate β-lactamase inhibitor with potent, selective, and direct inhibitory activity against Ambler class A, B, C, and D enzymes, including serine and metallo-β-lactamases. Taniborbactam has a broader spectrum of inhibition than any other current β-lactamase inhibitor. The combination of cefepime with taniborbactam is in advanced clinical development. Investigators are studying the activity of cefepime-taniborbactam against gram-negative pathogens, including Enterobacterales species like carbapenem-resistant Klebsiella pneumoniae and MDR Pseudomonas aeruginosa with characterized carbapenem resistance mechanisms. In this review, we discuss the advances in medicinal chemistry that led to the development of cefepime-taniborbactam, the pharmacokinetics and pharmacodynamics, the antimicrobial spectrum of activity, potential uses in the clinic, and mechanisms of resistance. We propose future clinical scenarios to better explore the precise niche of this novel inhibitor combination.