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In Vitro Selection of MRSA Strains Resistant to Some New Fluoroquinolone Antibiotics and Characterization of their Resistance Mechanisms  

Yoon, Eun-Jeong (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Kim, Hyun-Jee (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Lee, Chun-Yeong (Department of Life Science, University of Seoul)
Choi, Eung-Chil (College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University)
Shim, Mi-Ja (Department of Life Science, University of Seoul)
Publication Information
YAKHAK HOEJI / v.52, no.3, 2008 , pp. 219-224 More about this Journal
Abstract
Clinically isolated methicillin-resistant Staphylococcus aureus strains were exposed to subinhibitory concentration of DW286, DW-224a, gemifloxacin, trovafloxacin, sparfloxacin and ciprofloxacin during 26- to 39-days period. Subculturing led to resistance development, and most of the selected mutants were above susceptible breakpoints. Selected mutants had broad cross resistance to other quinolone antibiotics and only one mutant was completely susceptible to all fluoroquinolones. Twenty five among 42 mutants revealed mutations on DNA gyrase and topoisomerase IV by sequencing. Also 16 mutants had fluoroquinolones MICs that were 4-32 times lower in the presence of reserpine. In conclusion, alterations in DNA gyrase or topoisomerase IV and action of efflux pumping out system are the resistance mechanisms of DW-224a.
Keywords
quinolone; DNA gyrase; topoisomerase IV; MRSA; QRDR;
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1 Acar, J. F. and Francoual, S. : The clinical problems of bacterial resistance to the new quinolones. J. Antimicrob. Chemother. 26 Suppl B, 207 (1990)   DOI   PUBMED
2 Hamett, N., Brown, S. and Krishnan, C. : Emergence of quinolone resistance among clinical isolate of methicillinresistant Staphylococcus aureus in Ontario, Canada. Antimicrob. Agents Chemother. 35, 1911 (1991)   DOI   PUBMED   ScienceOn
3 Kosowska-Shick, K., Credito, K., Pankuch, G. A., Lin, Gengrong., Bozdogzn, B., McGhee, P., Dewasse, B., Choi, D. R., Ryu, J. M. and Appelbaum, P. C. : Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents. Antimicrob. Agents Chemother. 50, 2064 (2006)   DOI   ScienceOn
4 Kim, M. J., Yun, H. J., Kang, J. W., Kim, S., Kwak, J. H. and Choi, E. C. : In vitro development of resistance to a novel fluoroquinolone, DW286, in methicillin-resistant Staphylococcus aureus clinical isolates. J. Antimicrob. Chemother. 51, 1011 (2003)   DOI   ScienceOn
5 Yoshida, H., Bogaki, M., Nakamura, M., Yamanaka, L. M. and Nakamura, S. : Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli. Antimicrob. Agents Chemother. 35, 1647 (1991)   DOI   PUBMED   ScienceOn
6 Piddock, L. J. : Mechanisms of fluoroquinolone resistance: and update 1994-1998. Drugs 58 Suppl 2, 11 (1999)   PUBMED
7 Aeschlimann ,J. R., Dresser, L. D., Kaatz, G. W. and Rybak, M. J. : Effects of NorA inhibitors on in vitro antibacterial activities and postantibiotic effects of levofloxacin, ciprofloxacin, and norfloxacin in genetically related strains of Staphylococcus aureus. Antimicrob. Agents Chemother. 43, 335 (1999)   PUBMED
8 Daum, R. S. and Seal, J. B. : Evolving antimicrobial chemotherapy for Staphylococcus aureus infection: our backs to the wall. Crit. Care Med. 29 Suppl 4, N92 (2001)   DOI   ScienceOn
9 Clinical and Laboratory Standards Institute (CLSI), Performance standards for antimicrobial susceptibility testing; 15th informational Supplement. Document M100-S15, CLSI, Wayne, PA (2005)
10 Kwon, A. R., Min, Y. H., Ryu, J. M., Choi, D. R., Shim, M. J. and Choi, E. C. : In vitro and in vivo activities of DW-224a, a novel fluoroquinolone antibiotic agent. J. Antimicrob. Chemother. 58, 684 (2006)   DOI   ScienceOn
11 Weigel, L. M., Anderson, G. J., Facklam, R. R. and Tenover, F. C. : Genetic analyses of mutations contributing to fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. Antimicrob. Agents Chemother. 45, 3517 (2001)   DOI   ScienceOn
12 Ince, D. and Hooper, D. C. : Mechanisms and frequency of resistance to premafloxacin in Staphylococcus aureus: novel mutations suggest novel drug-target interactions. Antimicrob. Agents Chemother. 44, 3344 (2000)   DOI   ScienceOn
13 Tanaka, M., Wang, T., Onodera, Y., Uchida, Y. and Sato, K. : Mechanisms of quinolone resistance in Staphylococcus aureus. J. Infect. Chemother. 6, 131 (2000)   DOI   ScienceOn
14 Piddock, L. J. V. : Newer fluoroquinolones and Gram positive bacteria. ASM News 59, 603 (1993)
15 Chanbers, H. F. : The changing epidemiology of Staphylococcus aureus? Emerg. Infect. Dis. 7, 178 (2001)   DOI   PUBMED   ScienceOn
16 Park, H. S., Kim, H. J., Seol, M. J., Choi, D. R., Choi, E. C. and Kwak, J. H. : In vitro and in vivo antibacterial activities of DW-224a, a new fluoronaphthyridone Antimicrob. Agents Chemother. 50, 2261 (2006)   DOI   ScienceOn