Bactericidal activity of garenoxacin tested by kill-curve methodology against wild type and QRDR mutant strains of Streptococcus pneumoniae

Kill-curve bactericidal assays over 24 hours were determined for garenoxacin, a novel des-F(6) quinolone, and levofloxacin at achievable serum drug concentrations ranging from 2 to 8 mug/mL. Tested strains included 4 wild type and 2 target quinolone resistance-determining region (QRDR) mutant Streptococcus pneumoniae. Garenoxacin was 16-fold to 32-fold more active than levofloxacin, and mutant strains (3 QRDR sites) had garenoxacin minimum inhibitory concentration (MIC) values at 1 mug/mL (levofloxacin MIC >32 mug/mL, resistant), but equal to the levofloxacin potency against wild type strains. Garenoxacin killed mutant pneumococci with comparable rapidity, as did levofloxacin versus strains without target alterations. Garenoxacin appears to be a widely usable and highly active agent against S. pneumoniae resistant to other quinolones such as levofloxacin. (C) 2004 Elsevier Inc. All rights reserved.