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We evaluated the in vitro activity of sitafloxacin against Japanese clinical isolates of Streptococcus pyogenes by broth microdilution susceptibility testing and time-kill studies to elucidate its eradication potential against S. pyogenes. One hundred and nineteen clinical isolates of S. pyogenes isolated from pharynx were tested to sitafloxacin and seven other agents in the susceptibility testing. The time-kill studies were conducted with five strains, one of which was resistant to clarithromycin, one resistant to levofloxacin and one type strain of S. pyogenes. In the time-kill studies, sitafloxacin, garenoxacin, amoxicillin and clarithromycin were assessed at static concentrations of their respective peak concentrations in plasma (C(max)) when administered as oral single doses for adult patients with S. pyogenes infections. We found the rank order of antimicrobial activity against S. pyogenes isolates was: cefcapene (MIC90, 0.015 microg/mL) > amoxicillin (0.03 microg/mL) > sitafloxacin (0.12 microg/mL) > garenoxacin (0.25 microg/mL) > levofloxacin (4 microg/mL) > minocycline (16 microg/mL). Macrolide-resistant isolates accounted for 72 (60.5%), resulting in clarithromycin and azithromycin MIC90s of > 32 and > 128 microg/mL, respectively. Sitafloxacin exhibited the most rapid bactericidal activity (> or = log reduction from the initial inoculum) within 2h against all tested strains, including even one levofloxacin-resistant strain. For garenoxacin, bactericidal activity was achieved between 2 and 6 h. Amoxicillin revealed no significant bactericidal activity up to 6 h. Clarithromycin showed no bactericidal activity and did not inhibit growth of a clarithromycin-resistant strain. These data indicate the potential usefulness of sitafloxacin for the treatment of S. pyogenes eradication.