Resistance of Pseudomonas aeruginosa to new beta-lactamase-resistant beta-lactams.
An isogenic set of mutants of Pseudomonas aeruginosa, altered in permeability or permeability plus constitutive production of beta-lactamase, was examined for susceptibility to newer beta-lactam antibiotics. Kinetic data on the chromosomal beta-lactamase and susceptibility studies for the test beta-lactams indicate that permeability was the major mechanism of resistance to the poorly hydrolyzed and nonhydrolyzed antibiotics, e.g., carbenicillin, moxalactam, and cefsulodin. An exception was cefotaxime, with a low Km and a low Vmax, which had reduced efficacy in the permeability mutant and was further affected by the constitutive beta-lactamase. In this case, since the Vmax was low, a nonhydrolytic barrier may provide the additional reduction in susceptibility.
D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability; D004352:Drug Resistance, Microbial; D006868:Hydrolysis; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000494:pharmacology*; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases