A 2018-2019 patent review of metallo beta-lactamase inhibitors

Abstract

Introduction: Antibiotic resistance caused by beta-lactamase expressing bacteria poses a concern given its global dissemination and proliferation. The emergence of the metallo beta-lactamases is an indefinite health threat toward which current antibiotics have limited clinical efficacy. One solution is to develop metallo beta-lactamase inhibitors (MBLIs) capable of restoring the activity of beta-lactam drugs.

Areas covered: This review focuses on potential metallo beta-lactamase inhibitors that have been patented during the period of 2018-2019. The aim is to provide insight into the diverse class of compounds which exhibit a synergistic inhibitory effect on carbapenem-resistant bacteria, when co-administered with a beta-lactam antibiotic.

Expert opinion: The treatment strategy, of creating a broad-spectrum beta-lactamase inhibitor, is beneficial to the health sector as well as rural communities. Unfortunately, most of the inhibitors lack published data from both in vitro and in vivo evaluation, thus preventing an expert opinion on the likelihood to progress as candidates for clinical trials. From this report, the bismuth complexes, pyridinyl-nicotinamide derived sugars, boronic acid, and thiazole sulfonamide derivatives, portray promising properties for further advancement. Since there is currently no FDA approved MBLI, there remains an urgent need for the development of these combination treatment strategies.

Keywords: Beta-lactamase inhibitors; carbapenem resistant Enterobacteriaceae; metallo beta-lactamase inhibitors; serine beta-lactamase inhibitors.