Clinical development of QPX7728 has been initiated.ĭevelopment of β-lactamase inhibitors (BLIs) in combination with β-lactams continues to be a powerful strategy to restore potency of β-lactams against β-lactamase-producing bacteria, thus extending clinical utility of this important class of antibiotics ( Bush, 2018 Bush and Bradford, 2019 Ho et al., 2019 Papp-Wallace, 2019). QPX7728 can also be delivered orally thus, its ultra-broad β-lactamase inhibition spectrum and other features could be also applied to oral QPX7728-based combination products. This provides microbiological justification for a stand-alone BLI product for co-administration with different β-lactams.
aeruginosa, different partner β-lactams in combination with QPX7728 may be optimal for the coverage of susceptible organisms. QPX7728 combinations with several intravenous (IV) β-lactam antibiotics shows broad coverage of Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa, including strains that are resistant to other IV β-lactam-BLI combinations, e.g., ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam and imipenem-relebactam that were recently approved for clinical use. Importantly, it is minimally affected by general intrinsic resistance mechanisms such as efflux and porin mutations that impede entry of drugs into gram-negative bacteria. We show that QPX7728 is an ultra-broad-spectrum β-lactamase inhibitor with the broadest spectrum of inhibition reported to date in a single BLI molecule in addition to potent inhibition of clinically important serine β-lactamases, including Class A and D carbapenemases from Enterobacterales and notably, diverse Class D carbapenemases from Acinetobacter, it also inhibits many metallo β-lactamases. In this paper we provide the overview of the biochemical, structural and microbiological studies that were recently conducted with QPX7728. The first member of this class, vaborbactam, is a BLI in the recently approved Vabomere (meropenem-vaborbactam). QPX7728 is a novel β-lactamase inhibitor (BLI) that belongs to a class of cyclic boronates. 2Molsoft, LLC, San Diego, CA, United States.