Heterogeneity of beta-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen.
Twenty Pseudomonas maltophilia isolates were examined for susceptibility to beta-lactam antibiotics, including carbapenems, and for beta-lactamase production. All the isolates were resistant to imipenem (MICs 64-512 mg/l) and to a lesser extent, to meropenem (MICs 16-256 mg/l). None of the isolates produced significant amounts of beta-lactamase without induction. Among the beta-lactams studied imipenem proved to be the most potent inducer; meropenem was a weaker inducer. Interestingly, 6-amino-penicillanic acid, even in concentrations up to 100 mg/l, entirely lacked induction activity. In any case enzyme production was drug concentration dependent and transient. Isoelectric focusing revealed 6 different enzymes distinguished by their different isoelectric points (pH 6.2, 8.3, 8.5, 9.0, 9.2 and 9.4). This suggested the lack of a unique beta-lactamase profile in P. maltophilia. Addition of 5 mM cyclic AMP (cAMP) or 0.5 mM cAMP-N6, O2-dioctanoyl (a lipophilic derivative) resulted in a marked drop of beta-lactamase induction by imipenem as compared to the control assay. Monitoring of carbapenem hydrolysis by cell-free supernatants revealed inactivation of both carbapenems. Meropenem was inactivated about 5 times more rapidly than imipenem. Our studies revealed that beta-lactamase production in P. maltophilia as well as growth kinetics were influenced to a considerable extent by the nutrient medium employed.
Cullmann
W
W
Department of Medical Microbiology and Immunology, Ruhr-University, Bochum, FRG.
Dick
W
W
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015780:Carbapenems / Q000096:biosynthesis / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D004790:Enzyme Induction / Q000187:drug effects; D015378:Imipenem / Q000494:pharmacology; D007700:Kinetics; D000077731:Meropenem; D011549:Pseudomonas / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000302:isolation & purification; D013845:Thienamycins / Q000494:pharmacology; D001618:beta-Lactamases / Q000032:analysis / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins; D015378:Imipenem; D001618:beta-Lactamases; D000077731:Meropenem