Emergence of quinolone-imipenem cross-resistance in Pseudomonas aeruginosa after flooroqmnolone therapy

Abstract

Emergence of resistance to fluoroquinolones was observed in two clinical isolates of Pseudomonas aeruginosa after ciprofloxacin or norfloxarin monotherapy. In the first case, the resistant variants exhibited qumolone-imipenem cross-resistance (MIC of norfloxacin and ciprofloxacin: 16mg/L; MIC of imipenem: 8 mg/L), although the patient had never received imipenem treatment, while the strain from the second case remained imipenem-susceptible (MIC of norfloxacin or riprofloxadn: 8 mg/L; MIC of imipenem: 2 mg/I). The frequency of in-vitro emergence of variants resistant to imipenem and fluoroquinolones was studied for the two strains, with imipenem or fluoroquinolones as selecting agents. Ciprofloxacin and three other quinolones (norfloxacin, temafloxacin and tosufloxacin) selected imipenem-resistant variants in a similar way to imipenem for the first strain, but not for the other. In contrast, imipenem did not select quinolone-resistant variants from either strain. For both strains, killing curves demonstrated that a bactericidal effect could be obtained with a drug combination (2 × MIC of ciprofloxacin and 2 × MIC of imipenem) without any selection of resistant mutants after 24 h, thereby suggesting the possible use of this combined regimen for treating severe P. aeruginosa infection.