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.