Meeting the challenges of beta-lactamases.

A wide variety of beta-lactamases are found in clinical isolates of bacteria and, when present, these enzymes often result in resistance to one or more beta-lactam antibiotics. The prevalence of organisms with these enzymes has increased as beta-lactams have been increasingly used in clinical practice. This paper defines the nature of these enzymes and details the attempts to overcome the problem of resistance mediated by beta-lactamase, efforts which have culminated in the development of a series of effective beta-lactamase inhibitors which can be combined with beta-lactam antibiotics. The currently available compounds, clavulanic acid, sulbactam, and tazobactam are very effective inhibitors of many types of beta-lactamases, but there are additional enzymes which are resistant even to these inhibitors and which pose continuing challenges for the pharmaceutical chemist and clinician alike.