Beta-lactamases and beta-lactamase inhibitors.

Penicillin, the first of the beta-lactam antibiotics, was introduced into medical practice in the 1940s. Since then, a large number of different beta-lactams, including penicillins, cephalosporins, monobactams, and carbapenems, have been developed, all of which are structurally related through the presence of a core beta-lactam ring. Resistance to beta-lactam antibiotics among target pathogens developed early in the history of their use. Of the mechanisms of resistance, the most widespread and most important is the destruction 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 successfully with the use of beta-lactamase inhibitors. The combination of beta-lactams with beta-lactamase inhibitors restores the activity of the beta-lactams, allowing their continued clinical use. The development of beta-lactamase inhibitors allows clinicians to rely on the well-tolerated, clinically effective beta-lactam antibiotics to treat a variety of bacterial infections.