Beta-lactamase lability and inducer power of newer beta-lactam antibiotics in relation to their activity against beta-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.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001390:Azlocillin / Q000378:metabolism / Q000494:pharmacology; D002228:Carbenicillin / Q000378:metabolism / Q000494:pharmacology; D002439:Cefotaxime / Q000378:metabolism / Q000494:pharmacology; D002443:Ceftriaxone / Q000378:metabolism / Q000494:pharmacology; D004790:Enzyme Induction; D015378:Imipenem; D007700:Kinetics; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D013845:Thienamycins / Q000378:metabolism / Q000494:pharmacology; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000378:metabolism
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D015378:Imipenem; D002443:Ceftriaxone; D001618:beta-Lactamases; D002228:Carbenicillin; D001390:Azlocillin; D002439:Cefotaxime