title: Study of in vitro selected resistance of Pseudomonas aeruginosa to cefoperazone, ceftazidime, azthreonam and imipenem.
abstract: Ten strains of Pseudomonas aeruginosa were plated on agar containing cefoperazone, ceftazidime, azthreonam or imipenem alone and in combination with ampicillin or cefoxitin as inducers, and/or amikacin (MIC/4), according to Szybalsky. Regrowing colonies were randomly selected for MIC and MBC determinations. The numbers of regrowing colonies were occasionally increased by a beta-lactamase inducer, although amikacin significantly reduced it. Some 243 colonies were further studied. The most frequent phenotypes of resistance (195 mutants) were: resistance to cefoperazone, ceftazidime, azthreonam (99 regrowing colonies); resistance to cefoperazone, azthreonam (36); resistance to cefoperazone (17); resistance to cefoperazone, ceftazidime, azthreonam, imipenem (17). A total of 28/31 R mutants retained their phenotype after 15 subcultures in antibiotic-free medium. The mutants R cefoperazone, ceftazidime, azthreonam were studied by quantitative beta-lactamase evaluation in agar with substrate and non-substrate antibiotics, substrate profile study spectrophotometrically, crypticity study by comparing beta-lactamase activity of intact and sonicated cells spectrophotometrically, isoelectric focusing of sonicate extracts and dialysis experiments for trapping evaluation. These mutants were characterized by a 240-fold increase in beta-lactamase production (Pi = 8.7) and unchanged permeability. beta-lactamase trapping was demonstrated but could not explain alone the phenotype of resistance. These studies suggest that mutants constitutive for beta-lactamase production were easily selected in vitro. Amikacin was able significantly to prevent their emergence.
mesh_terms: D000583:Amikacin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001398:Aztreonam / Q000494:pharmacology; D002438:Cefoperazone / Q000494:pharmacology; D002442:Ceftazidime / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D015378:Imipenem; D010641:Phenotype; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D015378:Imipenem; D002438:Cefoperazone; D000583:Amikacin; D002442:Ceftazidime; D001618:beta-Lactamases; D001398:Aztreonam