Factors that Influence the Evolution of -Lactam Resistance in -Lactamase--Inducible Strains of Enterobacter cloacae and Pseudomonas aeruginosa

Induction ratios were determined for beta-lactamase-inducible strains of Enterobacter cloacae and Pseudomonas aeruginosa by using 10 beta-lactam agents. For E. cloacae, pre-incubation with ceftriaxone, cefoxitin, cefamandole, cefoperazone, or imipenem produced significantly larger amounts of beta-lactamase than did pre-incubation with moxalactam, clavulanate, ceftazidime, or aztreonam. For P. aeruginosa, imipenem was the best inducer, whereas ceftriaxone, piperacillin, cefoperazone, cefamandole, clavulanate, and aztreonam were poor beta-lactamase inducers. The rate of emergence of resistance by E. cloacae p99 and P. aeruginosa ATCC 27853 did not correlate with the induction ratio of the selecting agent; however, a strong correlation was noted between the mutation rate and the ratio of the MIC to the concentration of selecting antibiotic used. Emergence of resistance is related to the MIC of the antibiotic and the concentration of antibiotic used to select for resistance and is independent of the efficacy of the beta-lactam inducer. Resistant mutants arise through both beta-lactamase-dependent and -independent mechanisms.