Surveillance of Fluoroquinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa - Open Journal of Medical Microbiology

OJMM > Vol.3 No.2, June 2013

Surveillance of Fluoroquinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa ()

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DOI: 10.4236/ojmm.2013.32022 3,873 Downloads 7,043 Views Citations

Author(s)

Hideki Kobayashi, Miho Isozaki, Tatsuya Fukuda, Yojiro Anzai, Fumio Kato

Affiliation(s)

Pharmaceutical Unit, Ohashi Medical Center, Toho University, Tokyo, Japan.
School of Pharmaceutical Sciences, Toho University, Funabashi, Chiba, Japan.

ABSTRACT

Ciprofloxacin (CPFX) and pazufloxacin (PZFX) have strong antibacterial activity against Pseudomonas aeruginosa. We investigated the sensitivity of P. aeruginosa to CPFX and PZFX in 373 strains isolated from inpatients (321 strains) and outpatients (52 strains) during September 2010 to September 2011 at Toho University Ohashi Medical Center. The percentage of CPFX-non-susceptible (≥3.91 μg/mL) among inpatients was 22.4%, but that among outpatients was 1.9%. As the major resistance mechanism to fluoroquinolones in P. aeruginosa involves modification of type II topoisomerases (DNA gyrase and topoisomerase IV), we examined mutations in the quinolone-resistance-determining regions (QRDRs) of gyrA and parC of P. aeruginosa isolates. Among the 373 isolates, 73 isolates had reduced CPFX-susceptibility and 88 had reduced PZFX-susceptibility. Sequencing of gyrA and parC revealed base substitutions that resulted in amino acid replacements in QRDR of GyrA in 70 P. aeruginosa isolates, while Thr83Ile (in GyrA) and Ser87Leu (in ParC) substitutions were found in 12 strains. These replacements were clearly associated with reduced susceptibility to CPFX and PZFX. However, we also found strains with high MICs to quinolones without mutations in either gyrA or parC. We then investigated the effect of efflux pumps in CPFX-resistance in these isolates. In the presence of an efflux pump inhibitor, MIC values in 12 of 66 strains decreased to 1/2³. We also sequenced genes related to overexpression of efflux pumps, viz., mexZ, mexR, and nfxB. Eight of the strains without mutations in QRDRs had a mutation in mexZ, 7 strains had a mutation in mexR, but no mutation was identified in nfxB.

KEYWORDS

Pseudomonas aeruginosa; Fluoroquinolone Resistant; Type II Topoisomerases; Efflux Pump

Share and Cite:

H. Kobayashi, M. Isozaki, T. Fukuda, Y. Anzai and F. Kato, "Surveillance of Fluoroquinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa," Open Journal of Medical Microbiology, Vol. 3 No. 2, 2013, pp. 144-150. doi: 10.4236/ojmm.2013.32022.

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