Liposomal amphotericin B in the treatment of visceral leishmaniasis in immunocompetent patients

Abstract

The leishmaniases are protozoan diseases caused by Leishmania parasites. The first-line treatment of its visceral forms is pentavalent antimony (meglumine antimoniate or sodium stibogluconate), but toxicity is frequent with this drug. Moreover antimony unresponsiveness is increasing in Leishmania infantum and L. donovani foci, both in immunocompetent and in immunosuppressed patients. Amphotericin B is a polyene macrolide antibiotic that binds to sterols in cell membranes. It is the most active antileishmanial agent in use. Its infusion-related and renal toxicity may be reduced by lipid-based delivery. Liposomal amphotericin B (AmBisome); Gilead Science, Paris, France) seems to be less toxic than other amphotericin B lipid formulations (Amphocil); Liposome Technology Inc., Menlo Park, CA, USA, Amphotec); Ben Venue Laboratories Inc., Bedford, OH, USA). Optimal drug regimens of AmBisome) vary from one geographical area to another. In the Mediterranean Basin, a total dose of 18 mg/kg (3 mg/kg on days 1-5 and 3 mg/kg on day 10) could be used as first-line treatment of visceral leishmaniasis in immunocompetent patients. In immunocompromised patients, especially those co-infected with HIV, relapses are frequent with AmBisome), as with other drugs.

Liposomal amphotericin B in comparison to sodium stibogluconate for cutaneous infection due to Leishmania braziliensis

“…12 Amphotericin B deoxycholate and lipid-based amphotericin B products are well-established treatments for visceral leishmaniasis. 13 The latter formula is considered less nephrotoxic than nonliposomal amphotericin B because it specifically targets the macrophages in which the Leishmania parasites develop. 14 In our study, a dose of 3 mg/kg of the liposomal amphotericin (AmBisome) was given for 5 consecutive days, with a sixth dose on day 10.…”

Safety and Efficacy of Single Dose versus Multiple Doses of AmBisome® for Treatment of Visceral Leishmaniasis in Eastern Africa: A Randomised Trial

“…In addition, 95% efficacy was achieved with higher single doses (10 mg/kg) or when used in combination with miltefosine or paromomycin [10]. Although licensed and recommended for first-line treatment of VL in immunocompetent patients [11], Ambisome® use in eastern Africa has been mostly limited to second line treatment in a few centres mainly due to its high cost and cold storage requirements [12]. A small study with AmBisome® conducted in Kenya indicated higher doses were required than had been used in studies in India.…”

Production and Characterization of Stable Amphotericin-Resistant Amastigotes and Promastigotes of Leishmania mexicana

“…Thus, it has recently been suggested that AMB should replace antimonials as the drug of choice in Bihar (37). In addition, patients coinfected with Leishmania infantum visceral leishmaniasis and human immunodeficiency virus in resource-rich countries are usually treated with liposome-entrapped AMB (8,27). Guidelines for treatment with AMB and other antileishmanial drugs have been improved, which, in addition to better treatment of individual patients, should lead to fewer relapses and therefore a decreased risk of secondary resistance.…”