Combined treatment of miltefosine and paromomycin delays the onset of experimental drug resistance in Leishmania infantum

PLoS Neglected Tropical Diseases
Sarah HendrickxGuy Caljon

Abstract

Since miltefosine monotherapy against visceral leishmaniasis (VL) caused by Leishmania donovani has been discontinued in the Indian subcontinent due to an increase in the number of treatment failures, single dose liposomal amphotericin B is now advocated as a treatment option of choice. Paromomycin-miltefosine combination therapy can be used as substitute first-line treatment in regions without cold-chain potential. Previous laboratory studies in the closely related species Leishmania infantum have demonstrated that paromomycin monotherapy fairly rapidly selects for resistance producing a phenotype with increased fitness. Given the possible clinical implications of these findings for the current field situation, the present study aimed to identify the potential hazards of paromomycin-miltefosine combination therapy. Drug interaction studies using the fixed-ratio isobologram method revealed an indifferent interaction between paromomycin and miltefosine. In hamsters infected with L. infantum, the combination resulted in cumulative efficacy in reducing parasite burdens in the liver, spleen and bone marrow. Selected resistant lines against the single drugs did not display cross-resistance. When the intracellular amastigote stage wa...Continue Reading

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Citations

Sep 20, 2018·Revista Do Instituto De Medicina Tropical De São Paulo·Débora Cardozo Bonfim CarboneMaria Cláudia Silva
Nov 17, 2019·International Journal of Molecular Sciences·Rita CapelaFrancisca Lopes
Dec 31, 2019·The Journal of Antimicrobial Chemotherapy·S HendrickxG Caljon
Jul 1, 2020·Parasite Immunology·Sheetal Saini, Ambak Kumar Rai
Aug 21, 2019·International Journal for Parasitology. Drugs and Drug Resistance·Luiz Filipe Gonçalves-OliveiraCarlos Roberto Alves
Feb 24, 2021·Antimicrobial Agents and Chemotherapy·Valter V Andrade-NetoEduardo Caio Torres-Santos

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Methods Mentioned

BETA
biopsy

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