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JAC Advance Access published online on February 25, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg162
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Brief report

In vitro development of resistance to a novel fluoroquinolone, DW286, in methicillin-resistant Staphylococcus aureus clinical isolates

Mi-Jeong Kim 1, Hee-Jeong Yun 1, Jin-Wook Kang 1, Sunghoon Kim 1, Jin-Hwan Kwak 2, Eung-Chil Choi 1*

1 College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Shillim-Dong, Kwanak-Gu, Seoul 151-742
2 School of Life & Food Sciences, Handong Global University, Pohang, South Korea

* Corresponding author. E-mail: ecchoi{at}snu.ac.kr.

Received 4 December 2002 ; revised 8 January 2003 ; accepted 20 January 2003

Abstract

In vitro development of resistance to a novel fluoroquinolone, DW286, as well as to ciprofloxacin, gemifloxacin, sparfloxacin and trovafloxacin, was investigated in eight methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The strains were subcultured in subinhibitory concentrations of each agent during a 50 day period. Subculturing in most agents led to the selection of 37 mutants with increased MICs. The DW286 MICs were increased from 0.004-0.031 to 0.125-0.5 mg/L in five strains after 13-47 passages, and were not increased in three strains. The ciprofloxacin, gemifloxacin, sparfloxacin and trovafloxacin-selected mutants showed relatively weak cross-resistance to DW286. DNA sequencing analyses of all of the selected mutants revealed a few point mutations responsible for the high level of resistance, but actually these variations did not confer high resistance to fluoroquinolones. In the presence of reserpine, an inhibitor of the Gram-positive efflux pump, of 36 mutants 22 had two- to 16-fold lower ciprofloxacin MICs, and 20 had two- to 16-fold lower gemifloxacin MICs. However, sparfloxacin, trovafloxacin and DW286 were not good substrates for efflux pumps.

Keywords: DW286, fluoroquinolone, MRSA, antibiotic resistance
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