Beta-lactamase lability and inducer power of newer beta-lactam antibiotics in relation to their activity against beta-lactamase-inducibility mutants of Pseudomonas aeruginosa

J Infect Dis. 1987 Apr;155(4):775-82. doi: 10.1093/infdis/155.4.775.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Azlocillin / metabolism
  • Azlocillin / pharmacology
  • Carbenicillin / metabolism
  • Carbenicillin / pharmacology
  • Cefotaxime / metabolism
  • Cefotaxime / pharmacology
  • Ceftriaxone / metabolism
  • Ceftriaxone / pharmacology
  • Enzyme Induction
  • Imipenem
  • Kinetics
  • Mutation
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / enzymology
  • Pseudomonas aeruginosa / genetics
  • Thienamycins / metabolism
  • Thienamycins / pharmacology
  • beta-Lactamases / biosynthesis*
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Thienamycins
  • Imipenem
  • Ceftriaxone
  • beta-Lactamases
  • Carbenicillin
  • Azlocillin
  • Cefotaxime