Cross-resistance to meropenem, cephems, and quinolones in Pseudomonas aeruginosa

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Abstract
Multiple-drug-resistant mutants were isolated from Pseudomonas aeruginosa PAO1 on agar plates containing ofloxacin and cefsulodin. These mutants were four to eight times more resistant to meropenem, cephems, carbenicillin, quinolones, tetracycline, and chloramphenicol than the parent strain was. In contrast, these mutants showed no significant changes in their susceptibilities to all carbapenems except meropenem. In these mutants, the amounts of an outer membrane protein with an apparent molecular weight of 49,000 (designated OprM) were increased compared with the amount in PAO1. Multiple-drug-resistant mutants of this type were also isolated from PAO1 on agar plates containing meropenem. Approximately 5% of clinical isolates showed cross-resistance to meropenem, cephems, and quinolones, concomitant with overproduction of OprM. Moreover, these two phenotypes, i.e., multiple-drug resistance and overproduction of OprM, were cotransferable by transduction. These data suggest that overproduction of OprM is associated with cross-resistance to meropenem, cephems, and quinolones in P. aeruginosa. The ofloxacin-cefsulodin-resistant mutant required higher concentrations of meropenem to induce beta-lactamase than PAO1 did, indicating the possibility that this mutation involves decreased outer membrane permeability to meropenem.

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