Carbapenemase inhibitors

Carbapenemase inhibitors play a critically important role in prevention of carbapenem resistance. In the current review, based on studied articles from PubMed, Google Scholar and Scopus, we summarize the current state of carbapenemase inhibitors and their importance in clinical use. Clavulanic acid, sulbactam and tazobactam are traditional β-lactam\class A carbapenemase inhibitors. Avibactam; relebactam and boronic acid-based inhibitors including PRX7009, β-lactamase inhibitory protein II, Zinc01807204 and Zinc02318494 compounds are also novel and non-β-lactam\class A carbapenemase inhibitors. In the case of metallo-β-lactamase inhibitors, EDTA, thioester derivatives, propionic acid, maleic acid, succinic acid and phthalic acid derivatives are reputed inhibitors. There are limited oxacillinase (OXA) inhibitors because of the variability in amino acid sequence of OXAs. Boronic acid-based compounds and penicillin sulfone derivatives are promising candidates for the development of OXA-carbapenemase inhibitors. Although the prospect for non-β-lactam inhibitors is better, but the available inhibitors are mostly developed against plasmid-mediated carbapenemases, and other clinically important carbapenemases are increasing throughout the world. Despite in-vitro activity of aforementioned inhibitors, few of them are in clinical use. Side effects followed by inhibitors and also carbapenemase inhibitor resistance indicate the clinical need for development of novel, effective and nontoxic inhibitors to overcome carbapenemase-mediated resistance in bacteria.