JAC Advance Access originally published online on November 12, 2003
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Journal of Antimicrobial Chemotherapy (2003) 52, 920-924
© 2003 The British Society for Antimicrobial Chemotherapy
In vitro and in vivo activity of olamufloxacin (HSR-903) against Legionella spp.
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan
Received 6 May 2003; returned 12 July 2003; revised 24 September 2003; accepted 1 October 2003
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: fluoroquinolones, Legionnaires’ disease, Legionella pneumophila
* Corresponding author. Tel: +81-98-895-1144; Fax: +81-98-895-1414; E-mail: fhiga{at}med.u-ryukyu.ac.jp
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