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.
Moellering
R C
RC
New England Deaconess Hospital, Boston, Massachusetts 02215.
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects / Q000201:enzymology; D004352:Drug Resistance, Microbial / Q000502:physiology*; D006801:Humans; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases