Imipenem-induced resistance to antipseudomonal beta-lactams in Pseudomonas aeruginosa

Using clinical isolates of Pseudomonas aeruginosa, we studied the ability of imipenem to antagonize the activity of nine other antipseudomonal beta-lactam antimicrobial agents. Imipenem caused truncation of the zones of inhibition in a disk diffusion test for 91 to 100% of the strains, depending on the beta-lactam tested. Addition of subinhibitory concentrations of imipenem caused a fourfold or greater increase in MICs for 72 of 74 isolates and in 20 to 87% of the tests, again depending on the antibiotic tested. beta-Lactamase assays with both whole-cell suspensions and cell sonicates showed that exposure to subinhibitory concentrations of imipenem resulted in a beta-lactamase production supported the hypothesis that induction of beta-lactamase was responsible for antagonism. In hydrolysis studies with a beta-lactamase extract, most of the antagonized drugs were either not hydrolyzed or only poorly hydrolyzed. We conclude that imipenem induces significantly elevated levels of beta-lactamase in P. aeruginosa. This increase in beta-lactamase is associated with increased resistance of the organism to many other beta-lactam agents.