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JAC Advance Access originally published online on October 12, 2009
Journal of Antimicrobial Chemotherapy 2009 64(6):1234-1240; doi:10.1093/jac/dkp365
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Combined topical paromomycin and oral miltefosine treatment of mice experimentally infected with Leishmania (Leishmania) major leads to reduction in both lesion size and systemic parasite burdens

Marta Gontijo Aguiar1,2, Diana Lara Silva2, Fernando Antônio Nunan2, Elzíria Aguiar Nunan1, Ana Paula Fernandes3 and Lucas Antônio Miranda Ferreira1,*

1 Department of Pharmaceutics, Faculty of Pharmacy, Federal University Minas Gerais, Belo Horizonte, Brazil 2 Centro Universitário Newton Paiva, Belo Horizonte, Brazil 3 Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University Minas Gerais, Belo Horizonte, Brazil

Received 6 July 2009; returned 21 August 2009; revised 14 September 2009; accepted 17 September 2009

* Corresponding author. Tel: +55-31-3499-6939; Fax: +55-31-3499-6830; E-mail: lucas{at}farmacia.ufmg.br

Objectives: This study aimed to investigate the activity of the combination of topical paromomycin gel and oral miltefosine for the treatment of experimental cutaneous leishmaniasis caused by Leishmania (Leishmania) major.

Methods: The efficacy of the combination, evaluated by measuring lesion size and parasite burden in the skin and spleen, was assessed in BALB/c mice infected by L. (L.) major. Miltefosine was administered orally at 25 mg/kg/day for 10 days, while 10% paromomycin gel was applied topically twice a day for 10 days.

Results: Treatment of the experimentally infected animals with topical paromomycin + oral miltefosine combination induced a statistically significant reduction in lesion size and parasite burden in the skin, with complete healing of ulcers, as compared with those treated with oral miltefosine or placebo. Furthermore, topical paromomycin + oral miltefosine combination was as effective as topical paromomycin alone to reduce the lesion size and parasite load in lesions. However, the efficacy of the combination was significantly higher than that observed for the other treatments, including topical paromomycin alone, in reducing the parasite burden in spleen.

Conclusions: The combination of topical paromomycin gel and oral miltefosine provides an enhanced efficacy in the treatment of L. (L.) major-infected mice, thus presenting a significantly higher activity than that observed for the monotherapeutic regimens.

Keywords: cutaneous leishmaniasis , therapy , efficacy evaluation , animal model


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