Higa Futoshi, Arakaki Noriko, Tateyama Masao, Koide Michio, Shinzato Takashi, Kawakami Kazuyoshi, Saito Atsushi
First Department of Internal Medicine, Faculty of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
J Antimicrob Chemother. 2003 Dec;52(6):920-4. doi: 10.1093/jac/dkh001. Epub 2003 Nov 12.
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.
对氟喹诺酮类药物奥拉氟沙星（HSR - 903）针对嗜肺军团菌属的活性进行了体外和体内研究。针对81株不同的嗜肺军团菌属菌株（59株标准菌株和22株临床分离株），50%的分离株被抑制时的奥拉氟沙星最低抑菌浓度（MIC50）为0.008mg/L，这与司帕沙星相同，而红霉素、左氧氟沙星和环丙沙星的MIC50分别为0.25、0.032和0.032mg/L。奥拉氟沙星和司帕沙星（浓度为0.008mg/L）可抑制嗜肺军团菌80 - 045在J774.1巨噬细胞内的生长及随后的细胞毒性，而相同浓度的左氧氟沙星和环丙沙星则不能。当给感染的豚鼠口服奥拉氟沙星（5mg/kg体重）时，给药后2小时肺内峰值水平为3.02mg/kg，半衰期为3.41小时，药时曲线下面积（AUC0 - 12）为12.31mg·h/kg。用奥拉氟沙星（5mg/kg和1.25mg/kg，每日口服两次）治疗的动物，感染后2天肺内细菌负荷远低于用左氧氟沙星（与奥拉氟沙星剂量相同）或红霉素（10mg/kg，每日口服两次）治疗的动物。用奥拉氟沙星（5mg/kg，每日口服两次）治疗7天，12只感染嗜肺军团菌的豚鼠中有11只在感染后存活14天，用左氧氟沙星（5mg/kg，每日口服两次）治疗7天的所有12只豚鼠也存活14天。相比之下，用红霉素治疗的12只动物中只有2只存活，生理盐水组的11只中有10只死亡。在豚鼠军团病模型中，奥拉氟沙星与左氧氟沙星效果相当。这些数据值得进一步研究奥拉氟沙星是否可作为治疗军团菌感染的一种选择。
