title: Rapid bactericidal activity of sitafloxacin against Streptococcus pneumoniae.
abstract: The initial bactericidal activity of quinolones against Streptococcus pneumoniae at the concentration equivalent to their respective peak serum concentration (C(max)) and free drug fraction of C(max) (fC(max)) were investigated. The bactericidal activity of sitafloxacin (STFX), levofloxacin (LVFX), moxifloxacin (MFLX), and garenoxacin (GRNX) were compared by determining the actual killing of bacteria at C(max) and fC(max) for 1 and 2 hours based on the Japanese maximum dose per administration (100, 500, 400, and 400 mg, respectively). Against 4 quinolone-susceptible clinical isolates (wild-type), STFX with C(max) and fC(max) exhibited the most rapid bactericidal activity resulting in an average reduction of > or = 3.0 log10 colony forming units (CFU)/ mL in 1 hour. STFX with C(max) and fC(max) also showed the most rapid and potent bactericidal activity against 9 clinical isolates with single par (C/E) mutation, resulting in > or = 3.0 log10 CFU/mL average reduction in viable cells in 1 hour. STFX showed a statistically significant advantage in initial bactericidal activity over other quinolones for single mutants (P < 0.001). The propensity that the difference in the initial bactericidal activity between STFX and other quinolones was higher in single mutants than wild-type strains, was confirmed using S. pneumoniae ATCC49619 (wild-type) and its laboratory single parC mutant. As a result, STFX showed a similar rapid and potent initial bactericidal activity against both strains, while initial bactericidal activity for other quinolones was significantly reduced in the single mutant (P < 0.05). In conclusion, STFX has the most rapid and potent initial bactericidal activity against wild-type and single mutants of S. pneumoniae and its bactericidal activity is not affected by the presence of a single par mutation compared to LVFX, MFLX, and GRNX.
authors.affiliation: Biological Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., Tokyo.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kanda
authors.forename: Kazue
authors.initials: K
authors.lastname: Inoue
authors.forename: Ryo
authors.initials: R
authors.lastname: Okumura
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hoshino
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; C076246:sitafloxacin