beta-Lactamase expression and outer membrane protein changes in cefpirome-resistant and ceftazidime-resistant gram-negative bacteria

Abstract

Twenty-five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia stuartii) and five strains of Pseudomonas aeruginosa were exposed to various concentrations of cefpirome or ceftazidime in agar. Mutants with a greater than four-fold increase in the MIC were examined for changes in beta-lactamase expression and outer membrane protein (OMP) profile. Both agents selected mutants with decreased susceptibility to the selecting antibiotic and other beta-lactams at a frequency of 10(-7)-10(-8). The MICs of all beta-lactams were higher for the resistant mutants of E. cloacae and P. aeruginosa than for the other species. Both agents selected mutants expressing derepressed class I beta-lactamase, but this was more common with ceftazidime. Only a few mutants of P. aeruginosa and E. cloacae had an MIC of cefpirome that was above the recommended breakpoint concentration. Some mutant strains of Enterobacteriaceae lacked an OMP of molecular size similar to OmpF, but the MIC of cefpirome was below the breakpoint concentration for all these strains.