Journal Article

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

Futoshi Higa, Noriko Arakaki, Masao Tateyama, Michio Koide, Takashi Shinzato, Kazuyoshi Kawakami and Atsushi Saito

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 52, issue 6, pages 920-924
Published in print December 2003 | ISSN: 0305-7453
Published online December 2003 | e-ISSN: 1460-2091 | DOI:
In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.

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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.

Keywords: Keywords: fluoroquinolones, Legionnaires’ disease, Legionella pneumophila

Journal Article.  3457 words.  Illustrated.

Subjects: Medical Oncology ; Critical Care

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