Kim Jong-Hyun, Jung Suk-Yul, Lee Yang-Jin, Song Kyoung-Ju, Kwon Daeho, Kim Kyongmin, Park Sun, Im Kyung-Il, Shin Ho-Joon
Department of Microbiology, Ajou University School of Medicine, Youngtong-Gu, Suwon, Republic of Korea.
Antimicrob Agents Chemother. 2008 Nov;52(11):4010-6. doi: 10.1128/AAC.00197-08. Epub 2008 Sep 2.
Naegleria fowleri is a ubiquitous, pathogenic free-living amoeba; it is the most virulent Naegleria species and causes primary amoebic meningoencephalitis (PAME) in laboratory animals and humans. Although amphotericin B is currently the only agent available for the treatment of PAME, it is a very toxic antibiotic and may cause many adverse effects on other organs. In order to find other potentially therapeutic agents for N. fowleri infection, the present study was undertaken to evaluate the in vitro and in vivo efficacies of miltefosine and chlorpromazine against pathogenic N. fowleri. The result showed that the growth of the amoeba was effectively inhibited by treatment with amphotericin B, miltefosine, and chlorpromazine. When N. fowleri trophozoites were treated with amphotericin B, miltefosine, and chlorpromazine, the MICs of the drug were 0.78, 25, and 12.5 microg/ml, respectively, on day 2. In experimental meningoencephalitis of mice that is caused by N. fowleri, the survival rates of mice treated with amphotericin B, miltefosine, and chlorpromazine were 40, 55, and 75%, respectively, during 1 month. The average mean time to death for the amphotericin B, miltefosine, and chlorpromazine treatments was 17.9 days. In this study, the effect of drugs was found to be optimal when 20 mg/kg was administered three times on days 3, 7, and 11. Finally, chlorpromazine had the best therapeutic activity against N. fowleri in vitro and in vivo. Therefore, it may be a more useful therapeutic agent for the treatment of PAME than amphotericin B.
福氏耐格里阿米巴是一种普遍存在的致病性自由生活阿米巴；它是毒性最强的耐格里阿米巴物种，可在实验动物和人类中引起原发性阿米巴脑膜脑炎（PAME）。尽管两性霉素B是目前唯一可用于治疗PAME的药物，但它是一种毒性很强的抗生素，可能会对其他器官产生许多不良反应。为了寻找其他可能治疗福氏耐格里阿米巴感染的药物，本研究旨在评估米替福新和氯丙嗪对致病性福氏耐格里阿米巴的体外和体内疗效。结果表明，用两性霉素B、米替福新和氯丙嗪处理可有效抑制阿米巴的生长。当用两性霉素B、米替福新和氯丙嗪处理福氏耐格里阿米巴滋养体时，第2天药物的最低抑菌浓度分别为0.78、25和12.5μg/ml。在由福氏耐格里阿米巴引起的小鼠实验性脑膜脑炎中，用两性霉素B、米替福新和氯丙嗪处理的小鼠在1个月内的存活率分别为40%、55%和75%。两性霉素B、米替福新和氯丙嗪处理组的平均死亡时间为17.9天。在本研究中，发现当在第3、7和11天以20mg/kg的剂量给药三次时，药物效果最佳。最后，氯丙嗪在体外和体内对福氏耐格里阿米巴具有最佳治疗活性。因此，它可能是一种比两性霉素B更有用的治疗PAME的药物。
