Anti-acanthamoeba efficacy and toxicity of miltefosine in an organotypic skin equivalent.
OBJECTIVE
Acanthamoebae can cause infections of several organs, including eye, skin, lung and brain. Except for Acanthamoeba keratitis, these infections are linked to immunodeficiency. Treatment is generally problematic, due to the lack of sufficiently effective and also easily manageable drugs. In a previous study we discovered that miltefosine (hexadecylphosphocholine) is highly active against Acanthamoeba spp. in vitro. The aim of the current study was to evaluate the suitability of miltefosine for the topical treatment of Acanthamoeba infections.


METHODS
Storage life and time dependency, susceptibilities of opportunistic bacterial and fungal pathogens, and synergistic and adverse effects of combinations with other anti-Acanthamoeba substances were determined. Moreover, an organotypic skin equivalent was adapted for investigating the penetration of acanthamoebae into the epidermis and the human tissue tolerability of miltefosine.


RESULTS
It was shown that miltefosine can be stored as a 2 mM stock solution and also as a 50 microM dilution over a period of 12 months at 4 degrees C without any loss of activity. Efficacies against staphylococci and Candida albicans were established. Acanthamoebae were able to penetrate the skin equivalent within 24 h. This penetration was prevented by treatment with miltefosine, while miltefosine treatment was well tolerated by the skin equivalent.


CONCLUSIONS
Miltefosine has been approved for oral and topical treatment of leishmaniasis and may also be a promising candidate for the topical treatment of Acanthamoeba infections.
Walochnik
Julia
J
Department of Medical Parasitology, Institute of Hygiene, Medical University of Vienna, 1095 Vienna, Austria. julia.walochnik@meduniwien.ac.at
Obwaller
Andreas
A
Gruber
Florian
F
Mildner
Michael
M
Tschachler
Erwin
E
Suchomel
Miranda
M
Duchêne
Michael
M
Auer
Herbert
H
D000048:Acanthamoeba / Q000187:drug effects*; D000818:Animals; D000981:Antiprotozoal Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D066298:In Vitro Techniques; D010767:Phosphorylcholine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D012871:Skin Diseases / Q000469:parasitology*; D013210:Staphylococcus / Q000187:drug effects
D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine