Combination therapy with nitazoxanide and amphotericin B, Glucantime®, miltefosine and sitamaquine against Leishmania (Leishmania) infantum intracellular amastigotes.

Abstract Leishmaniasis is a neglected disease that affects poorest population mainly in developing countries, representing one of the major causes of mortality and morbidity. Therefore, efforts to find new chemotherapeutics for leishmaniasis remain a priority. Previous reports demonstrated the in vitro and in vivo antileishmanial activity of nitazoxanide, an antiprotozoan agent used in the treatment of infectious diarrhea. The present work was carried out to determine the effect of nitazoxanide in combination with current antileishmanial drugs. Mouse peritoneal macrophages were infected with Leishmania ( Leishmania ) infantum amastigotes in order to calculate the 50% and 90% inhibitory concentration values. Drug interactions were assessed with fixed ratio isobologram method and fractional inhibitory concentrations (FIC 50 and FIC 90 ); sum of FIC (ΣFIC 50 and ΣFIC 90 ) and overall mean ΣFIC ( x ΣFIC 50 and x ΣFIC 90 ) were calculated for each combination. The nature of interactions was classified according to the x ΣFIC 50 and x ΣFIC 90 . The combination between nitazoxanide and amphotericin B, Glucantime ® , miltefosine and sitamaquine showed x ΣFIC 50 values of 1.13, 0.83, 1.06 and 0.94, respectively, indicating additive interaction. Considering the in vitro activity of nitazoxanide and the obtained results, further in vivo studies may be considered to evaluate possible drug interactions in visceral leishmaniasis.