OBJECTIVES Antifungal treatment of uncommon filamentous fungal infections is problematic. This study determined the in vitro susceptibility of miltefosine, as a single agent and in combination with posaconazole or voriconazole, against these pathogens. METHODS Susceptibility to miltefosine of 34 uncommon filamentous fungi was tested using CLSI broth microdilution M38-A2 methodology. Twenty is...

cutaneous leishmaniasis is endemic in 88 different countries. there are an estimated 1.5 million new cases each year, with over 90% occurring in afghanistan, algeria, iran, iraq, saudi arabia, syria (old world) and in brazil and peru (new world). miltefosine is effective in vitro and in vivo against leishmania species and it was demonstrated efficacy in animals via the oral route. this study is...

T-cell-deficient nude mice infected with Leishmania donovani were treated with miltefosine and then given either no treatment or intermittent miltefosine. Intracellular visceral infection recurred in untreated mice but was suppressed by once- or twice-weekly oral administration of miltefosine. Miltefosine may be useful as oral maintenance therapy for T-cell-deficient patients with visceral leis...

Miltefosine has antifungal properties and potential for development as a therapeutic for invasive fungal infections. However, its mode of action in fungi is poorly understood. We demonstrate that miltefosine is rapidly incorporated into yeast, where it penetrates the mitochondrial inner membrane, disrupting mitochondrial membrane potential and leading to an apoptosis-like cell death. COX9, whic...

UNLABELLED The mechanism of miltefosine-resistance in Leishmania spp. has been partially determined in experimental resistant lines; however, studies using clinical isolates with different miltefosine susceptibilities are still needed. In our study, we used a proteomic 2D-DIGE/MS approach to study different protein abundances in miltefosine-sensitive and -resistant Leishmania infantum chagasi i...

The oral agent miltefosine has demonstrated a >95% cure rate in Indian visceral leishmaniasis. We performed a large, placebo-controlled study of miltefosine therapy (2.5 mg/kg per day orally for 28 days) against cutaneous leishmaniasis in Colombia and Guatemala. In regions in Colombia where Leishmania vianna panamensis is common, the per-protocol cure rates for miltefosine and placebo were 91% ...

Miltefosine was the first oral compound approved for visceral leishmaniasis chemotherapy, and its efficacy against Leishmania donovani has been well documented. Leishmania amazonensis is the second most prevalent species causing cutaneous leishmaniasis and the main etiological agent of diffuse cutaneous leishmaniasis in Brazil. Driven by the necessity of finding alternative therapeutic strategi...

The in vitro leishmanicidal activity of miltefosine® (Zentaris GmbH) was assessed against four medically relevant Leishmania species of Brazil: Leishmania (Leishmania) amazonensis, Leishmania (Viannia) braziliensis, Leishmania (Viannia) guyanensis and Leishmania (Leishmania) chagasi. The activity of miltefosine against these New World species was compared to its activity against the Old World s...

BACKGROUND Oral miltefosine has been shown to be non-inferior to first-line, injectable meglumine antimoniate (MA) for the treatment of cutaneous leishmaniasis (CL) in children. Miltefosine may be administered via in-home caregiver Directly Observed Therapy (cDOT), while patients must travel to clinics to receive MA. We performed a cost-effectiveness analysis comparing miltefosine by cDOT versu...

BACKGROUND Recent reports indicated high miltefosine treatment failure rates for visceral leishmaniasis (VL) on the Indian subcontinent. To further explore the pharmacological factors associated with these treatment failures, a population pharmacokinetic-pharmacodynamic study was performed to examine the relationship between miltefosine drug exposure and treatment failure in a cohort of Nepales...