A comparative evaluation of amphotericin B and sodium antimony gluconate, as first-line drugs in the treatment of Indian visceral leishmaniasis.

In a study to evaluate the relative efficacies of sodium antimony gluconate (SAG) and amphotericin B (AMB), each drug was used to treat 60 Indian cases of visceral leishmaniasis (VL). At the time of treatment, each case had recently been parasitologically confirmed. The patients received either 20 mg SAG/kg daily, by intramuscular injection, for 4 weeks, or 1 mg AMB/kg daily, infused slowly over 2 h, with no incremental dosage, for 20 days. The response of the patients was followed clinically and by the microscopical examination of bone-marrow aspirates (BMA). The infected macrophages in subsamples of the BMA collected pre-treatment were cultured so that the drug sensitivities of the parasites, to 20 microg SAG or 1 microg AMB/ml medium, could be determined in vitro. Other subsamples of the BMA were used to set up promastigote cultures that were then used to infect BALB/c mice. The responses of the mice to 5 days of treatment with SAG or AMB (at the same daily dosages as used in the clinical trials) were subsequently explored. SAG only cured 46.6% of the patients given the drug, only cleared amastigotes from 38.3% of the macrophage cultures, and only cured 53.3% of the infected mice. The corresponding values for AMB - 100%, 100% and 100% - were markedly higher (P <0.001 for each comparison). Although nine patients had to be withdrawn from the SAG group (all because of cardiac toxicity), all of the patients given AMB completed their treatment without any serious adverse effects (P <0.01). Two of the patients withdrawn from the SAG arm died shortly after their withdrawal; earlier withdrawal may have saved them. At least in the setting of the present study, AMB appears far superior to SAG as a first-line drug against VL and should replace it.