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

TY - JOUR

T1 - A comparison of the mechanisms of decreased susceptibility of aztreonam-resistant and ceftazidime-resistant Enterobacteriaceae

AU - Piddock, L J

AU - Traynor, E A

AU - Wise, R

PY - 1990/12

Y1 - 1990/12

N2 - 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.

AB - 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.

KW - Aztreonam

KW - Bacterial Outer Membrane Proteins

KW - Ceftazidime

KW - Culture Media

KW - Drug Resistance, Microbial

KW - Electrophoresis, Polyacrylamide Gel

KW - Enterobacteriaceae

KW - Microbial Sensitivity Tests

KW - Molecular Weight

KW - Mutation

KW - Phenotype

KW - beta-Lactamases

M3 - Article

C2 - 2081717

VL - 26

SP - 749

EP - 762

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 6

ER -