Type I -Lactamases of Gram-Negative Bacteria: Interactions with -Lactam Antibiotics

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Abstract
The interaction of type I β-lactamases with diverse β-lactam compounds representing cephalosporins, cephamycins, penicillins, penams, penems, carbapenems, monobactams, and clavams was examined by using various Enterobacteriaceae and Pseudomonas aeruginosa as sources ofthe enzymes. The ability of a given drug to reversibly induce β-lactamase was unrelated to its ability to select mutants stably derepressed for β-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 β-lactamase, whereas the activity of anionic cephalosporins and aztreonam was most affected.