In vitro susceptibility to miltefosine of amphotericin B-resistant Leishmania (Mundinia) martiniquensis

Parasitol Res. 2023 Dec;122(12):3027-3035. doi: 10.1007/s00436-023-07992-3. Epub 2023 Oct 5.

Abstract

Leishmania (Mundinia) martiniquensis is a newly described species that causes human visceral, disseminated, and mucocutaneous leishmaniases. Amphotericin B deoxycholate (AmpB) is the first-line drug for the treatment of leishmaniasis in Thailand; however, several relapse cases of leishmaniasis caused by L. martiniquensis have been documented. In this study, in vitro susceptibility to AmpB and miltefosine (MIL) of wild-type (before treatment, LSCM1) and two AmpB-resistant L. martiniquensis strains (an in vitro-induced AmpB-resistant strain, AmpBRP2i, and a relapse strain, LSCM1-6) were determined. Results reveal that the IC50 value and resistance index against both drugs of promastigotes and intracellular amastigotes of the AmpBRP2i and LSCM1-6 strains were statistically significantly higher than those of the LSCM1 strain suggesting that cross-resistance with MIL occurred in both AmpB-resistant strains. The results of this study advocate further investigation into mechanisms that involve the complex nature of AmpB/MIL resistance in L. martiniquensis and development of effective methods for the identification of the AmpB-resistant parasites to help delivery of appropriate treatments for patients and for epidemiological surveys to survey the potential spread of drug-resistant strains.

Keywords: Amphotericin B; Drug resistance; Leishmania martiniquensis; Miltefosine; Relapse; Thailand.

MeSH terms

  • Amphotericin B / pharmacology
  • Amphotericin B / therapeutic use
  • Antiprotozoal Agents* / pharmacology
  • Antiprotozoal Agents* / therapeutic use
  • Chronic Disease
  • Humans
  • Leishmania*
  • Leishmaniasis* / drug therapy
  • Leishmaniasis, Visceral* / parasitology
  • Phosphorylcholine / pharmacology
  • Phosphorylcholine / therapeutic use
  • Recurrence

Substances

  • Amphotericin B
  • miltefosine
  • Phosphorylcholine
  • Antiprotozoal Agents