Treatment of visceral leishmaniasis with intravenous pentamidine and oral fluconazole in an HIV-positive patient with chronic renal failure — a case report and brief review of the literature

Abstract

We report the case of an HIV-positive patient with visceral leishmaniasis and several relapses after treatment with the two first-line anti-leishmanial drugs, liposomal amphotericin B and miltefosine. End-stage renal failure occurred in 2007 when the patient was on long-term treatment with miltefosine. A relapse of leishmaniasis in 2008 was successfully treated with a novel combination regimen of intravenous pentamidine and oral fluconazole. Secondary prophylaxis with fluconazole monotherapy did not prevent parasitological relapse of leishmaniasis.

Visceral Leishmaniasis and HIV Coinfection in the Mediterranean Region

“…Experience with other drugs such as pentamidine or paromomycin is limited to clinical cases, and these are mainly administrated in combination with other drugs [72], [73].…”

“…However, data to assess the efficacy of antileishmanial combination therapy in VL/HIV patients are insufficient, and no clinical trials have been performed in the Mediterranean area [3]. Only isolated cases of combination regimens with pentamidine and fluconazol, miltefosine and sodium stibogluconate [72], [74], allopurionol and meglumine antimoniate [75], or LAB and the human recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) colony growth factor [76] have been published with good results, but they are insufficient to establish firm recommendations. Future research should probably be focused on regimens based on the combination of LAB and other second-line drugs such as miltefosine, paromomycin, or pentamidine.…”

Triazine as a promising scaffold for its versatile biological behavior

“…A real advancement in chemotherapy of protozoan infections was made more than four decades ago with the introduction of pentamidine for leishmania [112][113][114] and metronidazole for amoebiasis [115,116] that demands a renewed effort seeking the development of new antileishmanial and antiamoebic agents effective against the pathogenic parasite and non toxic to the human cells by considering the need for a new molecule. Earlier, pyrimidines were synthesized and evaluated as inhibitors of leishmanial and trypanosomal dihydrofolate reductase (DHFR) [117] that has been successfully used as a drug target in the area of parasitic diseases, but clinically showed less selectivity [118] due to the over expression of gene pteridine reductase (PTR1), that has ability to provide reduced pterins and folates.…”

Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP

“…Renal failure was observed when the patient was on long-term treatment with miltefosine. The combination regimen of intravenous pentamidine and oral fluconazole successfully cured the relapse of leishmaniasis [36]. Pentamidine was used as a secondary prophylactic agent to prevent relapse in four immunocompromised patients (three with HIV-1 and one with idiopathic CD4+-lymphopenia) with relapsing visceral leishmaniasis at the Hospital for Tropical Diseases, London [37].…”