Activities of azithromycin and amphotericin B against Naegleria flowleri in vitro and in a mouse model of primary amebic meningoencephalitis
Activities of azithromycin and amphotericin B against Naegleria flowleri in vitro and in a mouse model of primary amebic meningoencephalitis
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DOI：
10.1128/aac.47.2.524-528.2003
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发表时间：
2003-02-01
影响因子：
4.9
通讯作者：
Brenner, GM
中科院分区：
文献类型：
--
作者：
Goswick, SM;Brenner, GM
吸入含有自由生活的福氏耐格里阿米巴的淡水可能导致一种潜在的致命感染，称为原发性阿米巴脑膜脑炎。两性霉素B是治疗人类原发性阿米巴脑膜脑炎的唯一具有确定临床疗效的药物，但使用该药物治疗通常与对肾脏和其他器官的不良反应相关，并且并非所有接受两性霉素B治疗的患者都存活。我们研究了新的治疗药物的体外活性和体内疗效，试图确定其他有用的药物治疗原发性阿米巴脑膜脑炎。阿奇霉素已显示出体外抗阿米巴属的活性。和抗实验性弓形虫病的体内活性。本研究测定了阿奇霉素对N. Fowleri的MIC为13.4 μ M（10 μ g/ml），比阿替霉素B的MIC（0.108 μ M（0.1 μ g/ml））大123倍。阿奇霉素以75 mg/kg/天的剂量连续5天保护了100%感染福氏奈瑟氏菌的小鼠，而阿替霉素B以7.5 mg/kg/天的剂量连续5天仅保护了50%的小鼠，所有对照小鼠在28天的观察期内死亡。我们的结论是，阿奇霉素在体外和体内都有活性，对N。可能是治疗原发性阿米巴脑膜脑炎的有效补充。
Inhalation of fresh water containing the free-living ameba Naegleria fowleri may lead to a potentially fatal infection known as primary amebic meningoencephalitis. Amphotericin B is the only agent with established clinical efficacy in the treatment of primary amebic meningoencephalitis in humans, but therapy with this drug is often associated with adverse effects on the kidneys and other organs, and not all persons treated with amphotericin B have survived. We investigated the in vitro activity and in vivo efficacy of newer therapeutic agents in an attempt to identify other useful agents for treating primary amebic meningoencephalitis. Azithromycin has shown in vitro activity against Acanthamoeba spp. and in vivo activity against experimental toxoplasmosis. In our study, the MIC of azithromycin against N. fowleri was 13.4 muM (10 mug/ml), which was 123 times greater than the MIC of amphotericin B, which was 0.108 muM (0.1 mug/ml). Azithromycin protected 100% of mice infected with N.fowleri at a dose of 75 mg/kg/day for 5 days, whereas amphotericin B protected only 50% of mice at a dose of 7.5 mg/kg/day for 5 days, and all control mice died during the 28-day observation period. We conclude that azithromycin has both in vitro and in vivo activity versus N. fowleri and may be a useful addition to therapy for primary amebic meningoencephalitis.