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Journal of Antimicrobial Chemotherapy (1999) 44, 71-76
© 1999 The British Society for Antimicrobial Chemotherapy

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

C. Di Giorgioa,*, F. Faraut-Gambarellib, A. Imbertb, P. Minodierc, M. Gasqueta and H. Dumonb

,aLaboratoire de Parasitologie, Hygiène et Zoologie, Faculté de Pharmacie, 27 Bd. Jean Moulin, 13385 Marseille Cedex 05; ,bLaboratoire de Parasitologie, Faculté de Medecine; ,cService de Pédiatrie Pr. Garnier, Hôpital Nord, Marseille, France

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 (IC 90) 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 IC 90 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.

* Corresponding author. Tel: +33-04-91-83-55-44; Fax: +33-04-91-80-26-12.


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