Type I beta-lactamases of gram-negative bacteria: interactions with beta-lactam antibiotics

The interaction of type I beta-lactamases with diverse beta-lactam compounds representing cephalosporins, cephamycins, penicillins, penams, penems, carbapenems, monobactams, and clavams was examined by using various Enterobacteriaceae and Pseudomonas aeruginosa as sources of the enzymes. The ability of a given drug to reversibly induce beta-lactamase was unrelated to its ability to select mutants stably derepressed for beta-lactamase production. Imipenem was one of the most-potent enzyme inducers, yet it did not select derepressed mutants. Many of the newer cephalosporins were poor enzyme inducers but readily selected derepressed mutants. Resistance to hydrolysis did not predict a drug's inhibitory activity against derepressed mutants. The activity of the penems, penams, and carbapenems was least affected by derepression of beta-lactamase, whereas the activity of anionic cephalosporins and aztreonam was most affected.