Treatment of kala-azar in Brazil with AmphocilsR (amphotericin B cholesterol dispersion) for 5 days

Abstract

We have treated 10 patients suffering from kala-azar in Brazil with Amphocil (amphotericin B cholesterol dispersion) at a dose of 2 mg/kg/d for 5 d, following an earlier study in which this dosage for 7 d was found to cure all of 9 patients, with no relapse during 12 months. In the present study, all patients demonstrated initial resolution of disease. Parasites were absent upon bone marrow re-aspiration 2 weeks after therapy; no spleen extended beyond the costal margin 2 months after therapy; white blood cell counts, platelet counts, and serum levels of albumin rapidly returned to normal. Although one patient relapsed at 5 months, 8 of the other 9 patients had spleens of normal size (undetectable on deep palpation) at 12 months after therapy. Fever, sometimes accompanied by increased respiratory rate, occurred on the first day of drug infusion in 8 of 10 patients and was more severe in patients < 6 years old. Pre-medication with a non-steroidal anti-inflammatory agent (diclofenac potassium) before the next 4 infusions protected against this side effect in 5 of 6 patients. The results of this and our previous study suggest that the most appropriate regimen of Amphocil for kala-azar is 2 mg/kg/d for 7 d, with pre-medication each day, in patients aged > 5 years.

Failure of amphotericin B colloidal dispersion in the treatment of paracoccidioidomycosis.

“…A similar situation occurs with when attempting to treat leishmaniasis with lipid preparations of amphotericin B. Although lipid preparations of amphotericin B are highly effective against visceral leishmaniasis 5,6 (which primarily infects the reticuloendothelial system), they are ineffective against cutaneous leishmaniasis 9,10 (which primarily infects the dermis).…”

“…4 and visceral leishmaniasis. 5,6 Of note, many of these patients had failed prior therapy with either azoles or Fungizone.…”

Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis

“…The new formulations of amphotericin B provided the important opportunity to reduce duration of therapy in kala-azar while preserving efficacy (49,53,166); these formulations allow considerably higher daily doses of drug and simultaneously appear to target infected tissue macrophages via enhanced phagocytic uptake. Each of the three commercially available preparations, given once daily by infusion, is well tolerated and their usefulness in kala-azar has exceeded all clinical expectations (123).…”

“…Each of the three commercially available preparations, given once daily by infusion, is well tolerated and their usefulness in kala-azar has exceeded all clinical expectations (123). Provided sufficient total doses are administered, short-course regimens of as brief as 5 days (using daily infusions) or up to 10 days (during which five or six infusions are given) are remarkably active (49,53,169,176). Efficacy has been documented worldwide in children and adults and in severely ill patients under appalling conditions in war-torn Sudan (23,54,154).…”

In vitro and in vivo activity of amphotericin B-lipid formulations against experimental Trypanosoma cruzi infections.

“…Recently, lipid formulations that have lower toxicity have been developed for the treatment of systemic mycoses. 12,14,15 Three commercially available lipid formulations, the liposome AmBisome (NeXtar, San Dimas, CA), the colloidal dispersion Amphocil (Liposome Technology, Inc., Menlo Park, CA), and the lipid complex Abelcet (The Liposome Company, Ltd., London, United Kingdom), have also been shown to be effective against experimental [16][17][18][19] and clinical visceral leishmaniasis, [20][21][22] as well as against experimental cutaneous leishmaniasis. 23 In this study, the experimental activities of these three commercial lipid formulations of amphotericin B were compared with the parent drug, amphotericin B deoxycholate (Fungizone ; E. R. Squibb and Sons, Hounslow, United Kingdom) and the standard drug benznidazole, against experimental infections of T. cruzi in vitro and in vivo.…”