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Antimicrobial Agents and Chemotherapy, March 2003, p. 1023-1027, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1023-1027.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Mutant Prevention Concentration of Garenoxacin (BMS-284756) for Ciprofloxacin-Susceptible or -Resistant Staphylococcus aureus

Xilin Zhao, William Eisner, Nathan Perl-Rosenthal, Barry Kreiswirth, and Karl Drlica*

Public Health Research Institute, Newark, New Jersey 07103

Received 29 July 2002/ Returned for modification 24 September 2002/ Accepted 21 November 2002

The new quinolone garenoxacin (BMS-284756), which lacks a C-6 fluorine, was examined for its ability to block the growth of Staphylococcus aureus. Measurement of the MIC and the mutant prevention concentration (MPC) revealed that garenoxacin was 20-fold more potent than ciprofloxacin for a variety of ciprofloxacin-susceptible isolates, some of which were resistant to methicillin. The MPC for 90% of the isolates (MPC90) was below published serum drug concentrations achieved with recommended doses of garenoxacin. These in vitro observations suggest that garenoxacin has a low propensity for selective enrichment of fluoroquinolone-resistant mutants among ciprofloxacin-susceptible isolates of S. aureus. For ciprofloxacin-resistant isolates, the MIC at which 90% of the isolates tested were inhibited was below serum drug concentrations while the MPC90 was not. Thus, for these strains, garenoxacin concentrations are expected to fall inside the mutant selection window (between the MIC and the MPC) for much of the treatment time. As a result, garenoxacin is expected to selectively enrich mutants with even lower susceptibility.

* Corresponding author. Mailing address: Public Health Research Institute, 225 Warren St., Newark, NJ 07103-3535. Phone: (973) 854-3360. Fax: (973) 854-3101. E-mail: drlica{at}phri.org.

Antimicrobial Agents and Chemotherapy, March 2003, p. 1023-1027, Vol. 47, No. 3
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.3.1023-1027.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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