An update on beta-lactamase inhibitor discovery and development

Antibiotic resistance, and the emergence of pan-resistant clinical isolates, seriously threatens our capability to treat bacterial diseases, including potentially deadly hospital-acquired infections. This growing issue certainly requires multiple adequate responses, including the improvement of both diagnosis methods and use of antibacterial agents, and obviously the development of novel antibacterial drugs, especially active against Gram-negative pathogens, which represent an urgent medical need. Considering the clinical relevance of both beta-lactam antibiotics and beta-lactamase-mediated resistance, the discovery and development of combinations including a beta-lactamase inhibitor seems to be particularly attractive, despite being extremely challenging due to the enormous diversity, both structurally and mechanistically, of the potential beta-lactamase targets. This review will cover the evolution of currently available beta-lactamase inhibitors along with the most recent research leading to new beta-lactamase inhibitors of potential clinical interest or already in the stage of clinical development.