Title
In vivo selection of paromomycin and miltefosine resistance in **Leishmania donovani** and **L. infantum** in a Syrian hamster modelIn vivo selection of paromomycin and miltefosine resistance in **Leishmania donovani** and **L. infantum** in a Syrian hamster model
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Research group
Laboratory for Microbiology, Parasitology and Hygiene (LMPH)
Publication type
article
Publication
Washington, D.C.,
Subject
Biology
Pharmacology. Therapy
Human medicine
Source (journal)
Antimicrobial agents and chemotherapy. - Washington, D.C.
Volume/pages
59(2015):8, p. 4714-4718
ISSN
0066-4804
ISI
000362952000047
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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.
Full text (open access)
https://repository.uantwerpen.be/docman/irua/8fc392/a74f9f67.pdf
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