Heterogeneity of beta-lactamase production in Pseudomonas maltophilia, a nosocomial pathogen

Chemotherapy. 1990;36(2):117-26. doi: 10.1159/000238757.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Carbapenems / biosynthesis
  • Carbapenems / pharmacology
  • Drug Resistance, Microbial
  • Enzyme Induction / drug effects
  • Imipenem / pharmacology
  • Kinetics
  • Meropenem
  • Pseudomonas / drug effects
  • Pseudomonas / enzymology*
  • Pseudomonas / growth & development
  • Pseudomonas / isolation & purification
  • Thienamycins / pharmacology
  • beta-Lactamases / analysis
  • beta-Lactamases / biosynthesis*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Thienamycins
  • Imipenem
  • beta-Lactamases
  • Meropenem