Characterization of FCE 22101-resistant Enterobacteriaceae and the effect of FCE 22101 upon the activity of anti-pseudomonal beta-lactams for Pseudomonas aeruginosa

Twenty-five strains of Enterobacteriaceae (five each of Enterobacter cloacae, Citrobacter freundii, Serratia marcescens, Morganella morganii, and Providencia stuartii) were exposed to FCE 22101 in agar containing 3, 5, or 10 x the MIC. Any putative mutant with a greater than or equal to four-fold increase in the MIC was examined for beta-lactamase expression and outer membrane protein (OMP) profile. Mutant colonies were selected at a frequency of 10(-7)-10(-11) with decreased susceptibility to FCE 22101 and other beta-lactams, but after one subculture on antibiotic-free agar the mutants from 13 of the 25 strains reverted to wild-type. Only 19 stable mutants were selected from the other 12 wild-type strains, of which 15 lacked an OMP of similar molecular size to OmpF, and/or a low size OMP of approximately 18 kDa. None of the mutants had a significant alteration in expression of Richmond & Sykes class I beta-lactamase. In a separate section of the study in which 50 strains of Pseudomonas aeruginosa were examined, it was found that FCE 22101, at a concentration of 4 mg/L, induced beta-lactamase expression such that, after 24 h exposure, 24 of the 50 strains had a greater than or equal to four-fold rise in the MIC of several anti-pseudomonal beta-lactams.