Clofazimine, a Promising Drug for the Treatment of Babesia microti Infection in Severely Immunocompromised Hosts
Clofazimine, a Promising Drug for the Treatment of Babesia microti Infection in Severely Immunocompromised Hosts
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DOI：
10.1093/infdis/jiaa195
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发表时间：
2020-09-15
影响因子：
6.4
通讯作者：
Igarashi, Ikuo
中科院分区：
文献类型：
--
作者：
Tuvshintulga, Bumduuren;Vannier, Edouard;Igarashi, Ikuo
背景由小巴贝斯虫引起的持续性和复发性巴贝斯虫病经常发生在免疫功能低下的患者中，并且与对阿托伐醌等抗菌药物的耐药性有关。鉴于巴贝斯虫病在美国的发病率不断上升，迫切需要新型药物。在目前的研究中，我们测试了用于治疗麻风病和耐药结核病的抗生素氯法齐明（CFZ）是否对B有效。microti.Methods.用107 B感染重度联合免疫缺陷小鼠。感染的红细胞通过Giemsa染色血涂片显微镜检查或巢式聚合酶链反应检测寄生虫。CFZ口服给药。不间断的单药治疗CFZ减少了寄生虫血症的上升，并实现了根治。B。田鼠寄生虫和B.分别在治疗的第10天和第50天清除microti DNA。CFZ给药7天后，寄生虫血症的上升延迟了22天。这种上升是由B引起的。不携带细胞色素B基因突变的田鼠分离株。因此，CFZ给药14天足以解决阿托伐醌耐药B引起的高度寄生虫血症。田鼠寄生虫。结论。氯法齐明对B有效。免疫功能低下的宿主感染田鼠。需要额外的临床前研究来确定CFZ治疗巴贝虫病的最小剂量和剂量。
Background. Persistent and relapsing babesiosis caused by Babesia microti often occurs in immunocompromised patients, and has been associated with resistance to antimicrobial agents such as atovaquone. Given the rising incidence of babesiosis in the United States, novel drugs are urgently needed. In the current study, we tested whether clofazimine (CFZ), an antibiotic used to treat leprosy and drug-resistant tuberculosis, is effective against B. microti.Methods. Mice with severe combined immunodeficiency were infected with 107 B. microti-infected erythrocytes. Parasites were detected by means of microscopic examination of Giemsa-stained blood smears or nested polymerase chain reaction. CFZ was administered orally.Results. Uninterrupted monotherapy with CFZ curtailed the rise of parasitemia and achieved radical cure. B. microti parasites and B. microti DNA were cleared by days 10 and 50 of therapy, respectively. A 7-day administration of CFZ delayed the rise of parasitemia by 22 days. This rise was caused by B. microti isolates that did not carry mutations in the cytochrome b gene. Accordingly, a 14-day administration of CFZ was sufficient to resolve high-grade parasitemia caused by atovaquone-resistant B. microti parasites.Conclusions. Clofazimine is effective against B. microti infection in the immunocompromised host. Additional preclinical studies are required to identify the minimal dose and dosage of CFZ for babesiosis.