In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.
The activity of the fluoroquinolone olamufloxacin (HSR-903) against Legionella spp. was studied in vitro and in vivo. The olamufloxacin MIC at which 50% of isolates are inhibited (MIC50) for 81 different Legionella spp. strains (59 type strains and 22 clinical isolates) was 0.008 mg/L, which was identical to sparfloxacin, whereas the MIC50s for erythromycin, levofloxacin and ciprofloxacin were 0.25, 0.032 and 0.032 mg/L, respectively. Olamufloxacin and sparfloxacin (at 0.008 mg/L) inhibited intracellular growth and subsequent cytotoxicity of L. pneumophila 80-045 in J774.1 macrophages, whereas levofloxacin and ciprofloxacin did not, at the same concentration. When olamufloxacin was given to the infected guinea pigs orally (5 mg/kg of body weight), peak levels in the lung were 3.02 mg/kg at 2 h post-administration, with a half-life of 3.41 h and an AUC0-12 of 12.31 mg.h/kg. The 2 day post-infection bacterial burden of the lung in the animals treated with olamufloxacin (5 and 1.25 mg/kg given orally twice a day) was much lower than in those treated with levofloxacin (same dose as olamufloxacin) or erythromycin (10 mg/kg given orally twice a day). When treated with olamufloxacin (5 mg/kg given orally twice a day) for 7 days, 11 of 12 L. pneumophila-infected guinea pigs survived for 14 days post-infection, as did all 12 guinea pigs treated with levofloxacin (5 mg/kg given orally twice a day) for 7 days. In contrast, only two of 12 animals treated with erythromycin survived and 10 of 11 died in the physiological saline group. Olamufloxacin was as effective as levofloxacin in a guinea pig model of Legionnaires' disease. These data warrant further study of whether olamufloxacin is an option for the treatment of Legionella infections.
Higa
Futoshi
F
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan. fhiga@med.u-ryukyu.ac.jp
Arakaki
Noriko
N
Tateyama
Masao
M
Koide
Michio
M
Shinzato
Takashi
T
Kawakami
Kazuyoshi
K
Saito
Atsushi
A
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D019540:Area Under Curve; D002460:Cell Line; D004917:Erythromycin / Q000627:therapeutic use; D024841:Fluoroquinolones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D006168:Guinea Pigs; D006207:Half-Life; D007875:Legionella / Q000187:drug effects*; D007877:Legionnaires' Disease / Q000188:drug therapy* / Q000382:microbiology; D064704:Levofloxacin; D008264:Macrophages / Q000382:microbiology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000627:therapeutic use; D015363:Quinolones / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015363:Quinolones; D004917:Erythromycin; D064704:Levofloxacin; D015242:Ofloxacin; C106426:olamufloxacin