The impact of beta-lactamases on the development of novel antimicrobial agents.
beta-Lactamases have been critical factors for the selection and development of beta-lactam-containing antibacterial agents for almost 60 years. New agents under investigation continue to be evaluated based on their interactions with beta-lactamases. Oral carbapenems, penems and antimethicillin-resistant Staphylococcus aureus cephalosporins are all being selected for development, in part, because of their stability to hydrolysis by the beta-lactamases of their target organisms. beta-Lactamase inhibitors must selectively inhibit the major beta-lactamase groups appearing in current clinical isolates. For all agents, the multiplicity of beta-lactamases in single organisms or in mixed infections poses a new set of challenges requiring agents that can respond to enzymes with varying functional characteristics.
Bush
Karen
K
Johnson & Johnson Pharmaceutical Research & Development LLC, 1000 Route 202, Raritan, NJ 08869, USA. kbush@prdus.jnj.com
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000639:trends; 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