ArticleAntimicrobial agents and chemotherapy2015
In Vivo Selection of Paromomycin and Miltefosine Resistance in Leishmania donovani and L. infantum in a Syrian Hamster Model.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Safety and efficacy of short course combination regimens with AmBisome, miltefosine and paromomycin for the treatment of visceral leishmaniasis (VL) in Bangladesh.PLoS neglected tropical diseases · 2017Trial
- Repositioning of moxidectin: a promising approach in cutaneous leishmaniasis therapy.Parasite (Paris, France) · 2025Article
- Therapeutic success and failure in using miltefosine to treat dogs naturally infected with Leishmania infantum.Revista brasileira de parasitologia veterinaria = Brazilian journal of veterinary parasitology : Orgao Oficial do Colegio Brasileiro de Parasitologia Veterinaria · 2024Article
- Genome-wide analysis reveals allelic variation and chromosome copy number variation in paromomycin-resistant Leishmania donovani.Parasitology research · 2022Article
- Laboratory Selection of Trypanosomatid Pathogens for Drug Resistance.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Maximum levels of cross-contamination for 24 antimicrobial active substances in non-target feed. Part 2:EFSA journal. European Food Safety Authority · 2021Article
- Experimental Selection of Paromomycin Resistance inMicroorganisms · 2021Article
- Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series.Microorganisms · 2021Article
- Evaluation of the Pharmacophoric Role of the O-O Bond in Synthetic Antileishmanial Compounds: Comparison between 1,2-Dioxanes and Tetrahydropyrans.Journal of medicinal chemistry · 2020Article
- Antileishmanial Aminopyrazoles: Studies into Mechanisms and Stability of Experimental Drug Resistance.Antimicrobial agents and chemotherapy · 2020Article
- Impact of clinically acquired miltefosine resistance by Leishmania infantum on mouse and sand fly infection.International journal for parasitology. Drugs and drug resistance · 2020Article
- Can We Harness Immune Responses to Improve Drug Treatment in Leishmaniasis?Microorganisms · 2020Review
- Regulation of Translation in the Protozoan ParasiteInternational journal of molecular sciences · 2020Review
- Phenotypic adaptations of Leishmania donovani to recurrent miltefosine exposure and impact on sand fly infection.Parasites & vectors · 2020Article
- Immunosuppression of Syrian golden hamsters accelerates relapse but not the emergence of resistance in Leishmania infantum following recurrent miltefosine pressure.International journal for parasitology. Drugs and drug resistance · 2019Article
- Recent Development of Visceral Leishmaniasis Treatments: Successes, Pitfalls, and Perspectives.Clinical microbiology reviews · 2018Review
- Evaluating drug resistance in visceral leishmaniasis: the challenges.Parasitology · 2018Review
- Combined treatment of miltefosine and paromomycin delays the onset of experimental drug resistance in Leishmania infantum.PLoS neglected tropical diseases · 2017Article
- A Vaccine Therapy for Canine Visceral Leishmaniasis Promoted Significant Improvement of Clinical and Immune Status with Reduction in Parasite Burden.Frontiers in immunology · 2017Article
- Deep-sequencing revealing mutation dynamics in the miltefosine transporter gene in Leishmania infantum selected for miltefosine resistance.Parasitology research · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In 2002 and 2006, respectively, miltefosine (MIL) and paromomycin (PMM) were licensed in the Indian subcontinent for treatment of visceral leishmaniasis; however, their future routine use might become jeopardized by the development of drug resistance. Although experimental selection of resistant strains in vitro has repeatedly been reported using the less relevant promastigote vector stage, the outcome of resistance selection on intracellular amastigotes was reported to be protocol and species dependent. To corroborate these in vitro findings, selection of resistance in Leishmania donovani and Leishmania infantum was achieved by successive treatment/relapse cycles in infected Syrian golden hamsters. For PMM, resistant amastigotes were already obtained within 3 treatment/relapse cycles, while their promastigotes retained full susceptibility, thereby sharing the same phenotypic characteristics as in vitro-generated PMM-resistant strains. For MIL, even five treatment/relapse cycles failed to induce significant susceptibility changes in either species, which also corresponds with the in vitro observations where selection of an MIL-resistant phenotype proved to be quite challenging. In conclusion, these results argue for cautious use of PMM in the field to avoid rapid emergence of primary resistance and highlight the need for additional research on the mechanisms and dynamics of MIL resistance selection.
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