Beta-Lactamases Inhibitors: A Perspective on the Existing and the Potential Admixtures to Synergize Beta-lactams Versus Resistant Superbugs

Abstract

β-lactam antibiotics are considered the safest bactericides, and upon wide clinical use of benzyl penicillin G in 1945, outbreaks of resistance came out. The frequent semi-synthetic strategies revealed β-lactam generations that are of broad-spectrum activity. The new agents as well as their concomitant use with known inhibitors of β-lactamases potentiate their effectiveness versus higher numbers of resistant pathogens. However, the extremely resistant pathogens are still representing a burden. Efforts had been continued to find more inhibitors of β-lactamases to combine with β-lactams to provide good management of infections by extremely resistant microbes. The purpose of this work is to overview the conventional and the recently introduced β-lactamases in clinical applications, as well as some reported effective inhibitors of β-lactamases. The review pinpoints the inhibitors that can be mixed and/or merged with the beta-lactam antibiotics to effectively treat the microbial infections producing resistant-β-lactamases. ClogP for these drugs and candidate inhibitors is introduced as suggestions to open a door for developers to admix derivatives with suitable pharmacokinetics.