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 2-Jan and 1 × MIC in liquid medium for 22 h, and also to 3, 5 and 10 × MIC and 16 mg/l of each agent in agar. Any putative mutant with an increase in the MIC of {succeeds or equal to} 4 fold was examined for β-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 β-lactamase. For the Ent. cloacae mutants increased β-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 β-lactamase expression, as in species such as M. morganii. Hence the major mechanism of resistance in these strains would appear to be β-lactamase mediated rather than due to altered expression of outer membrane proteins. © 1990, by The British Society for Antimicrobial Chemotherapy.