A comparison of the mechanisms of decreased susceptibility of aztreonam-resistant and ceftazidime-resistant Enterobacteriaceae

J Antimicrob Chemother. 1990 Dec;26(6):749-62. doi: 10.1093/jac/26.6.749.

Abstract

Twenty five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii and Providencia stuartii) were exposed to aztreonam and ceftazidime at 1/2 and 1 x MIC in liquid medium for 22 h, and also to 3, 5 and 10 x MIC and 16 mg/l of each agent in agar. Any putative mutant with an increase in the MIC of greater than or equal to 4 fold was examined for beta-lactamase expression and outer membrane protein profile. Mutants were selected on agar at approximately 10(7); however in liquid medium not all strains yielded mutants. Mutants lacking an outer membrane protein (OMP) with a molecular weight of 40,000 (+/- 5000) were selected with both agents, as were mutants expressing constitutive Richmond and Sykes Class 1 beta-lactamase. For the Ent. cloacae mutants increased beta-lactamase gave rise to MICs above the breakpoint of both agents, whereas with the other species ceftazidime susceptibility was more affected. Strains that were OMP- rarely had MICs above the breakpoint, unless there was also increased beta-lactamase expression, as in species such as M. morganii. Hence the major mechanism of resistance in these strains would appear to be beta-lactamase mediated rather than due to altered expression of outer membrane proteins.

Publication types

  • Comparative Study

MeSH terms

  • Aztreonam / pharmacology*
  • Bacterial Outer Membrane Proteins / chemistry
  • Bacterial Outer Membrane Proteins / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Ceftazidime / pharmacology*
  • Culture Media
  • Drug Resistance, Microbial
  • Electrophoresis, Polyacrylamide Gel
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / genetics*
  • Microbial Sensitivity Tests
  • Molecular Weight
  • Mutation
  • Phenotype
  • beta-Lactamases / chemistry
  • beta-Lactamases / metabolism

Substances

  • Bacterial Outer Membrane Proteins
  • Culture Media
  • Ceftazidime
  • beta-Lactamases
  • Aztreonam