A comparison of the mechanisms of decreased susceptibility of aztreonam-resistant and ceftazidime-resistant Enterobacteriaceae.
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.
Piddock
L J
LJ
Department of Medical Microbiology, University of Birmingham, UK.
Traynor
E A
EA
Wise
R
R
D001398:Aztreonam / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002442:Ceftazidime / Q000494:pharmacology*; D003470:Culture Media; D004352:Drug Resistance, Microbial; D004591:Electrophoresis, Polyacrylamide Gel; D004755:Enterobacteriaceae / Q000187:drug effects / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008970:Molecular Weight; D009154:Mutation; D010641:Phenotype; D001618:beta-Lactamases / Q000737:chemistry / Q000378:metabolism
D001425:Bacterial Outer Membrane Proteins; D003470:Culture Media; D002442:Ceftazidime; D001618:beta-Lactamases; D001398:Aztreonam