Clofazimine, a promising drug for the treatment of Babesia microti infection in severely immunocompromised hosts.

Persistent and relapsing babesiosis caused by Babesia microti often occurs in immunocompromised patients; it 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. Herein, we tested whether clofazimine, an antibiotic used to treat leprosy and drug-resistant tuberculosis, is effective against B. microti.Mice with severe combined immunodeficiency were infected with 107B. microti-infected erythrocytes. Parasites were detected by microscopic examination of Giemsa-stained blood smears or nested PCR. Clofazimine was administered orally.Uninterrupted monotherapy with clofazimine curtailed the rise of parasitemia and achieved radical cure. B. microti parasites and B. microti DNA were cleared by day 10 and day 50 of therapy, respectively. A 7-day-long administration of clofazimine 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-long administration of clofazimine was sufficient to resolve high-grade parasitemia caused by atovaquone-resistant B. microti parasites.Clofazimine is effective against B. microti infection in the immunocompromised host. Additional pre-clinical studies are required to identify minimal dose and dosage of clofazimine for babesiosis.