-Lactamase Lability and Inducer Power of Newer -Lactam Antibiotics in Relation to Their Activity Against -Lactamase-Inducibility Mutants of Pseudomonas aeruginosa

The interactions of imipenem, carbenicillin, cefotaxime, ceftriaxone, and azlocillin with the chromosomal beta-lactamase of Pseudomonas aeruginosa were compared. Imipenem was hydrolyzed very slowly (kcat, 1/min) and induced beta-lactamase synthesis strongly. Its minimal inhibitory concentrations (MICs) reflected this behavior, being equal (1-2 micrograms/ml) for enzyme-inducible strains and their stably derepressed mutants. Mutants that had basal (i.e., minimal and uninducible) enzyme production were eight- to 16-fold more susceptible to imipenem than were inducible or stably derepressed strains. Carbenicillin was stable to hydrolysis (kcat, less than 0.1/min) and induced weakly at low concentrations. Consequently its MICs were equal for beta-lactamase-inducible strains and for their basal mutants. Stable beta-lactamase derepression generally did not increase resistance to carbenicillin significantly. Azlocillin, cefotaxime, and ceftriaxone were labile to hydrolysis (kcat, 12-297/min) but induced poorly. Consequently their MICs for enzyme-inducible strains equaled those for basal mutants but were elevated for derepressed mutants.