JAC Advance Access originally published online on June 23, 2009
Journal of Antimicrobial Chemotherapy 2009 64(3):539-545; doi:10.1093/jac/dkp215
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Original research |
Anti-Acanthamoeba efficacy and toxicity of miltefosine in an organotypic skin equivalent
1 Department of Medical Parasitology, Institute of Hygiene, Medical University of Vienna, Kinderspitalgasse 15, 1095 Vienna, Austria 2 Orphanidis Pharma Research GmbH, Wilhelminenstr. 91/IIf, 1160 Vienna, Austria 3 Department of Dermatology, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, Austria 4 Centre de Recherches et d'Investigations Epidermiques et Sensorielles (CERIES), 92521 Neuilly, France 5 Department of Decontamination, Institute of Hygiene, Medical University of Vienna, Kinderspitalgasse 15, 1095 Vienna, Austria 6 Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology, Pathophysiology and Immunology, Medical University of Vienna, Kinderspitalgasse 15, 1095 Vienna, Austria
Received 12 February 2009; returned 16 March 2009; revised 1 April 2009; accepted 27 May 2009
* Corresponding author. Tel: +43-1-40490-79446; Fax: +43-1-40490-79435; E-mail: julia.walochnik{at}meduniwien.ac.at
Objectives: 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 µM dilution over a period of 12 months at 4°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.
Keywords: amoebae , emerging diseases , immunosuppression , infection models , treatment