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

Mi Jeong Kim, Hee Jeong Yun, Jin Wook Kang, Sunghoon Kim, Jin Hwan Kwak, Eung Chil Choi

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1011-1016
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume51
Issue number4
DOIs
Publication statusPublished - 2003 Apr 1

Bibliographical note

Funding Information:
We are grateful to Pfizer Pharmaceuticals for supplying the trovafloxacin. This work was supported by the Basic Research Program of the Korea Science & Engineering Founda-

Funding Information:
tion, grant no. R01-1999-00110, and was partially supported by grant HMP-00-CH-15-0014 from the Korean Ministry of Health & Welfare and the BK21 project for Medicine, Dentistry, and Pharmacy.

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'In vitro development of resistance to a novel fluoroquinolone, DW286, in methicillin-resistant Staphylococcus aureus clinical isolates'. Together they form a unique fingerprint.

Cite this