beta-Lactamases and beta-lactamase inhibitors

Penicillin, the first of the beta-lactam antibiotics, was introduced into m edical practice in the 1940s. Since then, a large number of different beta- lactams, including penicillins, cephalosporins, monobactams, and carbapenem s, have been developed, all of which are structurally related through the p resence of a core beta-lactam ring. Resistance to beta-lactam antibiotics a mong target pathogens developed early in the history of their use. Of the m echanisms of resistance, the most widespread and most important is the dest ruction of the beta-lactam ring, which is mediated by beta-lactamases. The fact that these resistance enzymes may be coded on plasmids means that they are mobile within a bacterial community, and that they have spread widely. Resistance to beta-lactams mediated by beta-lactamases can be overcome suc cessfully with the use of beta-lactamase inhibitors. The combination of bet a-lactams with beta-lactamase inhibitors restores the activity of the beta- lactams, allowing their continued clinical use. The development of beta-lac tamase inhibitors allows clinicians to rely on the well-tolerated, clinical ly effective beta-lactam antibiotics to treat a variety of bacterial infect ions (C) 1999 Published by Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.