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Combined suboptimal schedules of topical paromomycin, meglumine antimoniate and miltefosine to treat experimental infection caused by Leishmania (Viannia) braziliensis.
J Antimicrob Chemother. 2015 Dec; 70(12):3283-90.JA

Abstract

OBJECTIVES

This study aimed to evaluate the efficacy of binary combinations of suboptimal schedules of drugs with different administration routes (topical paromomycin, intramuscular meglumine antimoniate and oral miltefosine) to treat animals infected with Leishmania (Viannia) braziliensis.

METHODS

Hamsters were inoculated with L. (V.) braziliensis and after ulceration of lesions, divided into seven groups: untreated control, paromomycin, miltefosine, meglumine antimoniate, meglumine antimoniate + paromomycin, miltefosine + paromomycin and meglumine antimoniate + miltefosine. Meglumine antimoniate and miltefosine were administered at low doses and topical paromomycin at a single daily application regimen. The animals were treated for 20 consecutive days (meglumine antimoniate and/or paromomycin) and/or 10 alternate days (miltefosine). Lesion sizes were determined weekly. Upon completion of treatment, parasites were recovered from skin lesions and spleens and evaluated by limiting dilution assay.

RESULTS

The combinations of a once daily application of paromomycin with low doses of miltefosine or meglumine antimoniate yielded higher efficacies in reducing the parasite load as well as lesion size when compared with any of these drugs administered as monotherapy regimens at the same suboptimal schedules.

CONCLUSIONS

Considering the parameters evaluated, the combinations of a systemic therapy with topical treatment were more effective than monotherapy with each of these drugs. These combinations may represent an alternative combination strategy for the treatment of leishmaniasis caused by L. (V.) braziliensis.

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Publisher Full Text (DOI)

Authors+Show Affiliations

de Morais-Teixeira E
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
Aguiar MG
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Soares de Souza Lima B
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil.
Ferreira LA
Department of Pharmaceutics, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Rabello A
Laboratório de Pesquisas Clínicas-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz-FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil ana@cpqrr.fiocruz.br.

MeSH

Administration, OralAdministration, TopicalAnimalsAntiprotozoal AgentsAppointments and SchedulesDisease Models, AnimalDrug Therapy, CombinationInjections, IntramuscularLeishmania braziliensisLeishmaniasis, CutaneousMaleMeglumineMeglumine AntimoniateMesocricetusOrganometallic CompoundsParomomycinPhosphorylcholineSkinSpleenTreatment Outcome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26346991

Citation

de Morais-Teixeira, Eliane, et al. "Combined Suboptimal Schedules of Topical Paromomycin, Meglumine Antimoniate and Miltefosine to Treat Experimental Infection Caused By Leishmania (Viannia) Braziliensis." The Journal of Antimicrobial Chemotherapy, vol. 70, no. 12, 2015, pp. 3283-90.
de Morais-Teixeira E, Aguiar MG, Soares de Souza Lima B, et al. Combined suboptimal schedules of topical paromomycin, meglumine antimoniate and miltefosine to treat experimental infection caused by Leishmania (Viannia) braziliensis. J Antimicrob Chemother. 2015;70(12):3283-90.
de Morais-Teixeira, E., Aguiar, M. G., Soares de Souza Lima, B., Ferreira, L. A., & Rabello, A. (2015). Combined suboptimal schedules of topical paromomycin, meglumine antimoniate and miltefosine to treat experimental infection caused by Leishmania (Viannia) braziliensis. The Journal of Antimicrobial Chemotherapy, 70(12), 3283-90. https://doi.org/10.1093/jac/dkv254
de Morais-Teixeira E, et al. Combined Suboptimal Schedules of Topical Paromomycin, Meglumine Antimoniate and Miltefosine to Treat Experimental Infection Caused By Leishmania (Viannia) Braziliensis. J Antimicrob Chemother. 2015;70(12):3283-90. PubMed PMID: 26346991.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined suboptimal schedules of topical paromomycin, meglumine antimoniate and miltefosine to treat experimental infection caused by Leishmania (Viannia) braziliensis. AU - de Morais-Teixeira,Eliane, AU - Aguiar,Marta Gontijo, AU - Soares de Souza Lima,Bruna, AU - Ferreira,Lucas Antônio Miranda, AU - Rabello,Ana, Y1 - 2015/09/07/ PY - 2015/04/06/received PY - 2015/07/21/accepted PY - 2015/9/9/entrez PY - 2015/9/9/pubmed PY - 2016/8/27/medline SP - 3283 EP - 90 JF - The Journal of antimicrobial chemotherapy JO - J Antimicrob Chemother VL - 70 IS - 12 N2 - OBJECTIVES: This study aimed to evaluate the efficacy of binary combinations of suboptimal schedules of drugs with different administration routes (topical paromomycin, intramuscular meglumine antimoniate and oral miltefosine) to treat animals infected with Leishmania (Viannia) braziliensis. METHODS: Hamsters were inoculated with L. (V.) braziliensis and after ulceration of lesions, divided into seven groups: untreated control, paromomycin, miltefosine, meglumine antimoniate, meglumine antimoniate + paromomycin, miltefosine + paromomycin and meglumine antimoniate + miltefosine. Meglumine antimoniate and miltefosine were administered at low doses and topical paromomycin at a single daily application regimen. The animals were treated for 20 consecutive days (meglumine antimoniate and/or paromomycin) and/or 10 alternate days (miltefosine). Lesion sizes were determined weekly. Upon completion of treatment, parasites were recovered from skin lesions and spleens and evaluated by limiting dilution assay. RESULTS: The combinations of a once daily application of paromomycin with low doses of miltefosine or meglumine antimoniate yielded higher efficacies in reducing the parasite load as well as lesion size when compared with any of these drugs administered as monotherapy regimens at the same suboptimal schedules. CONCLUSIONS: Considering the parameters evaluated, the combinations of a systemic therapy with topical treatment were more effective than monotherapy with each of these drugs. These combinations may represent an alternative combination strategy for the treatment of leishmaniasis caused by L. (V.) braziliensis. SN - 1460-2091 UR - https://www.unboundmedicine.com/medline/citation/26346991/Combined_suboptimal_schedules_of_topical_paromomycin_meglumine_antimoniate_and_miltefosine_to_treat_experimental_infection_caused_by_Leishmania__Viannia__braziliensis_ DB - PRIME DP - Unbound Medicine ER -