Novel ß-Lactamase Inhibitors: New Weapons in the Arms Race against Antimicrobial Resistance

Antimicrobial resistance is a growing threat in the treatment of infectious diseases. Multidrug-resistant Gram-negative organisms, in particular, have become progressively difficult to manage, due to the increasing diversity and widespread prevalence of β-lactamase enzymes. Novel β-lactamase inhibitors with expanded activity against such enzymes represent a promising strategy to combat Gram-negative resistance. This review discusses the classification of β-lactamases and the history of β-lactamase inhibitor development with a focus on three novel β-lactamase inhibitors—avibactam, relebactam, and vaborbactam—now FDA approved in combination β-lactam/β-lactamase inhibitor products available for clinical use, including their spectrums of inhibition, mechanisms of action, place in therapy, and evidence for use.