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Surveillance of Fluoroquinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa

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DOI: 10.4236/ojmm.2013.32022    2,902 Downloads   5,294 Views   Citations

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.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

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.

References

[1] M. D. Obritsch, D. N. Fish, R. MacLaren and R. Jung, “Nosocomial Infections Due to Multidrug-Resistant Pseudomonas aeruginosa: Epidemiology and Treatment Options,” Pharmacotherapy, Vol. 25, No. 10, 2005, pp. 1353-1364. doi:10.1592/phco.2005.25.10.1353
[2] T. Strateva and D. Yordanov, “Pseudomonas aeruginosa— A Phenomenon of Bacterial Resistance,” Journal of Medical Microbiology, Vol. 58, No. 9, 2009, pp. 1133-1148. doi:10.1099/jmm.0.009142-0
[3] H. P. Hahn, “The Type-4 Pilus Is the Major Virulence-Associated Adhesin of Pseudomonas aeruginosa,” Gene, Vol. 192, No. 1, 1997, pp. 99-108. doi:10.1016/S0378-1119(97)00116-9
[4] L. L. Blackwood, R. M. Stone, B. H. Iglewski and J. E. Pennington, “Evaluation of Pseudomonas aeruginosa Exotoxina and Elastase as Virulence Factors in Acute Lung Infection,” Infection and Immunity, Vol. 39, No. 1, 1983, pp. 198-201.
[5] R. H. George, “Pseudomonas Infections in Cystic Fibrosis,” Archives of Disease in Childhood, Vol. 62, pp. 438-439. doi:10.1136/adc.62.5.438
[6] R. Mittal, S. Sharma, S. Chhibber and K. Harjai, “A Time Course Study of Production of Virulence Factors by Biofilms of Pseudomonas aeruginosa,” American Journal of Biomedical Sciences, Vol. 1, No. 3, 2009, pp. 178-187. doi:10.5099/aj090300178
[7] R. E. W. Hancock and D. P. Speert, “Antibiotic Resistant in Pseudomonas aeruginosa: Mechanisms and Impact on Treatment,” Drug Resistance Updates, Vol. 3, No. 4, 2000, pp. 247-255. doi:10.1054/drup.2000.0152
[8] E. Paramythiotou, J. C. Lucet, J. F. Timsit, D. Vanjak, C. Paugam-Burtz, J. L. Trouillet, S. Belloc, N. Kassis, A. Karabinis and A. Andremont, “Acquisition of Multidrug-Resistant Pseudomonas aeruginosa in Patients in Intensive Care Units: Role of Antibiotics with Antipseudomonal Activity,” Clinical Infectious Diseases, Vol. 38, No. 5, 2004, pp. 670-677. doi:10.1086/381550
[9] V. Aloush, S. Navon-Venezia, Y. Seigman-Igra, S. Cabili and Y. Carmeli, “Multidrug-Resistant Pseudomonas aeruginosa: Risk Factors and Clinical Impact,” Antimicrob Agents and Chemotherapy, Vol. 50, No. 1, 2006, pp. 43-48. doi:10.1128/AAC.50.1.43-48.2006
[10] D. L. Paterson, “The Epidemiological Profile of Infections with Multidrug-Resistant Pseudomonas aeruginosa and Acinetobacter Species,” Clinical Infectious Diseases, Vol. 43, Suppl. 2, 2006, pp. S43-S48. doi:10.1086/504476
[11] S. Cabili and Y. Carmeli, V. Aloush, S. Navon-Venezia and Y. Seigman-Igra, “Multidrug-Resistant Pseudomonas aeruginosa: Risk Factors and Clinical Impact Antimicrob,” Antimicrobial Agents and Chemotherapy, Vol. 50, No. 1, 2006, pp. 43-48. doi:10.1128/AAC.50.1.43-48.2006
[12] E. Paramythiotou, J.-C. Lucet, J.-F. Timsit, D. Vanjak, C. Paugam-Burtz, J.-L. Trouillet, S. Belloc, N. Kassis, A. Karabinis and A. Andremont, “Acquisition of Multidrug-Resistant Pseudomonas aeruginosa in Patients in Intensive Care Units: Role of Antibiotics with Antipseudomonal Activity,” Clinical Infectious Diseases, Vol. 38, No. 5, 2004, pp. 670-677. doi:10.1086/381550
[13] I. Yoshida, T. Fujimura, Y. Itoh, M. Tachibana, M. Kaku, K. Kanemitsu, C. Takahashi, J. Shiotani, Y. Ono, H. Baba, S. Matsuo, S. Asari, K. Matsuoka, N. Kusano, M. Nose, T. Saikawa, K. Hiramatsu, S. Kohno, Y. Hirakata, N. Yamane, I. Nakasone and Y. Yamano, “Antimicrobial Susceptibility of Clinical Isolates of Aerobic Gram-Negative Bacteria in 2004,” Japanese Journal of Chemotherapy, Vol. 56, No. 5, 2008, pp. 562-579.
[14] N. Abe, M. Komatsu, M. Iwasaki, Y. Nagasaka, S. Fu-kuda and S. Matsuo, “In Vitro Activity of Antimicrobial Agents against Clinical Isolates of Pseudomonas aeruginosa,” The Japanese Journal of Antibiotics, Vol. 58, No. 5, 2005, pp. 445-451.
[15] A. Kanayama, M. Kida, T. Iyoda, K. Matsuzaki, S. Shibuya, M. Hasegawa, T. Saika, F. Ikeda and I. Kobayashi, “Annual Changes in Drug Susceptibility of Pseudomonas aeruginosa Isolated from Blood and Other Clinical Specimens,” Japanese Journal of Chemotherapy, Vol. 58, No. 1, 2010, pp. 7-13.
[16] D. C. Hooper, “Fluoroquinolone Resistance among Gram-Positive Cocci,” The Lancet Infectious Diseases, Vol. 2, No. 9, 2002, pp. 530-538. doi:10.1016/S1473-3099(02)00369-9
[17] X.-S. Pan, J. Ambler, S. Mehtar and L. M. Fisher, “Involvement of Topoisomerase IV and DNA Gyrase as Ciprofloxacin Targets in Streptococcus pneumonia,” Antimicrobial Agents and Chemotherapy, Vol. 40, No. 10, 1996, pp. 2321-2326.
[18] L. M. Weige, C. D. Steward and F. C. Tenover, “gyrA Mutations Associated with Fluoroquinolone Resistance in Eight Species of Enterobacteriaceae,” Antimicrobial Agents and Chemotherapy, Vol. 42, No. 10, 1998, pp. 2661-2667.
[19] R. M. Salma, F. A. Dabboussi, I. O. Kassaa, R. H. Khudary and M. M. Hamze, “GyrA and ParC Mutations in Quinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa from Nini Hospital in North Lebanon,” Journal of Infection and Chemotherapy, Vol. 19, No. 1, 2013, pp. 77-81.
[20] J. Kriengkauykiat, E. Porter, O. Lomovskaya and A. Wong-Beringer, “Use of an Efflux Pump Inhibitor to Determine the Prevalence of Efflux Pump-Mediated Fluoroquinolone Resistance and Multidrug Resistance in Pseudomonas aeruginosa,” Antimicrobial Agents and Chemotherapy, Vol. 49, No. 2, 2005, pp. 565-570. doi:10.1128/AAC.49.2.565-570.2005
[21] M. Nakano, T. Deguchi, T. Kawamura, M. Yasuda, M. Kimura, Y. Okano and Y. Kawada, “Mutations in the gyrA and parC Genes in Fluoroquinolone-Resistant Clinical Isolates of Pseudomonas aeruginosa,” Antimicrobial Agents and Chemotherapy, Vol. 41, No. 10, 1997, pp. 2289-2291.
[22] H. Mouneimné, J. Robert, V. Jarlier and E. Cambau, “Type II Topoisomerase Mutations in Ciprofloxacin-Resistant Strains of Pseudomonas aeruginosa,” Antimicrobial Agents and Chemotherapy, Vol. 43, No. 1, 1999, pp. 62-66.
[23] P. G. Higgins, A. C. Fluit, D. Milatovic, J. Verhoef and F.-J. Schmitz, “Mutations in GyrA, ParC, MexR and NfxB in Clinical Isolates of Pseudomonas aeruginosa,” International Journal of Antimicrobial Agents, Vol. 21, No. 5, 2003, pp. 409-413. doi:10.1016/S0924-8579(03)00009-8
[24] G. G. Zhanel, J. A. Karlowsky, M. H. Saunders, et al., “Development of Multiple Antibiotic-Resistant (MAR) Mutants of Pseudomonas aeruginosa after Serial Exposure to Fluoroquinolones,” Antimicrobial Agents and Chemotherapy, Vol. 39, No. 2, 1995, pp. 489-495. doi:10.1128/AAC.39.2.489

  
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