Flow cytometric assessment of amphotericin B susceptibility in Leishmania infantum isolates from patients with visceral leishmaniasis

• Published in: Journal of antimicrobial chemotherapy 1999-07, Vol.44 (1), p.71-76
• Main Authors: DI GIORGIO, C, FARAUT-GAMBARELLI, F, IMBERT, A, MINODIER, P, GASQUET, M, DUMON, H
• Format: Article
• Language: English
• Subjects: Acquired Immunodeficiency Syndrome - complications; Adult; AIDS/HIV; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Analysis; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Biological and medical sciences; Child, Preschool; Drug Resistance; Fat Emulsions, Intravenous - therapeutic use; Flow Cytometry; General pharmacology; Humans; Immunocompetence; Immunocompromised Host; Infant; Leishmania infantum; Leishmania infantum - drug effects; Leishmania infantum - growth & development; Leishmaniasis, Visceral - drug therapy; Leishmaniasis, Visceral - parasitology; Medical sciences; Membrane Potentials - drug effects; Monocytes - drug effects; Monocytes - parasitology; Pharmacology. Drug treatments
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/44.1.71

Amphotericin B susceptibility was measured by a flow cytometric membrane potential assay in Leishmania infantum promastigotes isolated from 11 immunocompetent children treated with liposomal amphotericin B and 19 HIV-infected young adults treated with intralipid amphotericin B. Susceptibility levels were measured by the 90% inhibitory concentrations (IC90) representing the concentrations of drug that induced a 90% decrease in membrane potential compared with the control culture. In immunocompetent children, treatment was fully effective whatever the susceptibility of isolates to amphotericin B. In immunocompromised adults, on the contrary, unresponsiveness and relapses could be observed in all cases and IC90 increased in the course of successive treatments: a decrease of amphotericin B susceptibility in both promastigote and amastigote forms could be observed in a patient who had six relapses. These results suggest that the success of amphotericin B treatment depends greatly on patient immunity status, and indicate that successive relapses could enhance emergence of amphotericin B resistant isolates. The results demonstrate that the flow cytometric membrane potential assay can be used as an easy and reliable tool for studying the evolution of interactions between amphotericin B and the parasite membrane during long-term treatments.