Meningoencephalitis caused by the free-living amebae Naegleria fowleri, Acanthamoeba spp., or Balamuthia mandrillaris, usually acquired through the nose while swimming in warm fresh water, has a mortality rate of >90% despite treatment with multiple antimicrobial drugs.2 Miltefosine is active against free-living amebae in vitro, and addition of the drug has improved survival in a small number of patients with Acanthamoeba spp. or B. mandrillaris infection. Infection with N. fowleri is especially severe; of 128 people known to be infected in the US since 1962, only one has survived. Miltefosine has not yet been shown to successfully treat N. fowleri infection.

Miltefosine is also used for treatment of visceral, cutaneous and mucosal leishmaniasis,2 and may soon be approved by the FDA for this indication.