Work

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

Year: 2003

Type: article

Abstract: 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 (MPC(90)) 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 MPC(90) 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.

Source: Antimicrobial Agents and Chemotherapy

DOI: 10.1128/aac.47.3.1023-1027.2003

Authors: Xilin Zhao, William Eisner, Nathan Perl-Rosenthal, Barry Kreiswirth, Karl Drlica

Language: English

Topic: Antimicrobial Resistance in Staphylococcus

Subfield: Infectious Diseases

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Bristol-Myers Squibb, National Institutes of Health, National Institute of Allergy and Infectious Diseases

Awards: G5671493092, G9000285324, G904364918