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JAC Advance Access published online on September 21, 2007
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkm361
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© The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Susceptibilities of healthcare- and community-associated methicillin-resistant staphylococci to the novel des-F(6)-quinolone DX-619

Shinya Watanabe1, Teruyo Ito1,2,* and Keiichi Hiramatsu1,2

1 Department of Infection Control Science, Graduate School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan 2 Department of Bacteriology, School of Medicine, Juntendo University, 2-1-1 Hongo, Bunkyo-ku, Tokyo, Japan

Received 1 May 2007; returned 28 June 2007; revised 23 August 2007; accepted 24 August 2007

* Corresponding author. Tel: +81-3-5802-1041; Fax: +81-3-5684-7830; E-mail: teruybac{at}med.juntendo.ac.jp

Objectives: The aim of the study was to test in vitro activities of the novel des-F(6)-quinolone DX-619 against methicillin-resistant staphylococci (MRS) isolated in hospitals and communities and to compare its activity with other quinolones, sitafloxacin and levofloxacin, and antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus infection, including vancomycin, teicoplanin, arbekacin, linezolid and quinupristin/dalfopristin.

Methods: MICs were determined by the agar dilution method using healthcare-associated MRS (S. aureus including strains with reduced susceptibility to vancomycin, 103; coagulase-negative staphylococci, 87) and community-associated MRS (S. aureus including non-multiresistant oxacillin-resistant strains, 37; coagulase-negative staphylococci, 92). The quinolone resistance-determining regions of gyrA, gyrB, grlA and grlB genes from six strains with reduced susceptibility to DX-619 were sequenced.

Results: DX-619 showed the lowest MIC90 values for all categories of strains tested, irrespective of the degree of glycopeptide resistance. The six strains with MIC values of >128 mg/L of levofloxacin commonly carried two mutations in gyrA and two mutations in grlA. DX-619 showed potent activity against strains with MIC values of 2 mg/L.

Conclusions: DX-619 was potent against all MRS tested, suggesting that it would be a promising candidate for the treatment of methicillin-resistant S. aureus infection if sufficient in vivo concentrations were safely attained.

Key Words: Staphylococcus aureus , coagulase-negative staphylococci , antimicrobial activity , gyrA , grlA


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