In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.

Abstract

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.

• Authors: Futoshi Higa, Noriko Arakaki, Masao Tateyama, Michio Koide, Takashi Shinzato, Kazuyoshi Kawakami, Atsushi Saito
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 52 Issue 6 Pg. 920-4 (Dec 2003) ISSN: 0305-7453 [Print] England
• PMID: 14613952 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Bacterial Agents
• Fluoroquinolones
• Quinolones
• Erythromycin
• Levofloxacin
• Ofloxacin
• olamufloxacin

Topics

• Animals
• Anti-Bacterial Agents (pharmacokinetics, pharmacology, therapeutic use)
• Area Under Curve
• Cell Line
• Erythromycin (therapeutic use)
• Fluoroquinolones (pharmacokinetics, pharmacology, therapeutic use)
• Guinea Pigs
• Half-Life
• Legionella (drug effects)
• Legionnaires' Disease (drug therapy, microbiology)
• Levofloxacin
• Macrophages (microbiology)
• Male
• Mice
• Microbial Sensitivity Tests
• Ofloxacin (therapeutic use)
• Quinolones (pharmacokinetics, pharmacology, therapeutic use)