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

Abstract

The interactions of imipenem, carbenicillin, cefotaxime, ceftriaxone, and azlocillin with the chromosomal β-lactamase of Pseudomonas aeruginosa were compared. Imipenem was hydrolyzed very slowly (k_cat, 1/min) and induced β-lactamase synthesis strongly. Its minimal inhibitory concentrations (MICs) reflected this behavior, being equal (1–2 μg/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 de repressed strains. Carbenicillin was stable to hydrolysis (k_cat, k_cat, 12–297/min) but induced poorly. Consequently their MICs for enzyme-inducible strains equaled those for basal mutants but were elevated for derepressed mutants.