Effect of QRDR Mutations on Ciprofloxacin Resistance in Clinical Isolates of Pseudomonas aeruginosa

Background & objectives: Fluoroquinolones have important role in treatment of P. aeruginosa infections. The main mechanism of fluoroquinolones resistance in P. aeruginosa is mutations in the quinolone-resistance-determining region (QRDR) of gyrA and parC genes. The aim of this study was to investigate the role of these mutations in ciprofloxacin resistance in different clinical isolates of P. aeruginosa. Methods: A total of 75 clinical P. aeruginosa isolates were collected from different university-affiliated hospitals in Tabriz. Minimum inhibitory concentrations (MICs) of ciprofloxacin were evaluated by Etest assay. DNA sequences of the QRDR of gyrA and parC were determined by dideoxy chain termination method. Results: From 75 isolates, 77.33% were resistant to ciprofloxacin. No amino acid changes were detected in gyrA or parC genes of the ciprofloxacin susceptible isolates. Thr-83&rarr;Ile substitution in gyrA was observed in all ciprofloxacin resistant isolates. About 90% of them had Ser-87&rarr;Leu substitution in parC. Geometric mean MICs of ciprofloxacin were different for various clinical isolates of P. aeruginosa which had the same situation in type and location of gyrA and parC mutations. Moreover, the geometric mean MIC in isolates from urine was significantly (p<0.05) higher than isolates from tracheal aspirates. Conclusion: Mutations in gyrA and parC genes are the major mechanisms for ciprofloxacin resistance in clinical isolates of P. aeruginosa. Moreover, the role of different effective factors in fluoroquinolone resistance can be different in various clinical isolates of P. aeruginosa