Abstract:A randomized trial of amphotericin B (AB) alone and in combination with oral itraconazole (IZ) is carried out in two groups of 10 mucocutaneous leishmaniasis patients from Bolivia and Peru. AB+IZ combination is no better than AB monotherapy, as far as efficacy and tolerability are concerned. No antagonism was detected
“…The experimental results were not satisfactory, but clinical tests indicated promising results for this drug as a last resort in relapsing cases 96 . Therefore, more studies were carried out focusing on the treatment of ATL 97,98 . The combination of itraconazole and amphotericin was not superior to the use of the latter alone.…”
Although pentavalent antimonials are the drugs of choice in the treatment of CL, pentamidine showed similar results. Nevertheless, several aspects, such as cost, adverse effects, local experience, and availability of drugs to treat CL, must be considered when determining the best management of this disease, especially in developing countries where resources are scarce.
“…The experimental results were not satisfactory, but clinical tests indicated promising results for this drug as a last resort in relapsing cases 96 . Therefore, more studies were carried out focusing on the treatment of ATL 97,98 . The combination of itraconazole and amphotericin was not superior to the use of the latter alone.…”
Although pentavalent antimonials are the drugs of choice in the treatment of CL, pentamidine showed similar results. Nevertheless, several aspects, such as cost, adverse effects, local experience, and availability of drugs to treat CL, must be considered when determining the best management of this disease, especially in developing countries where resources are scarce.
“…Itraconazole has been evaluated previously for the treatment of MCL. More rapid and efficient healing was observed in some cases of MCL when itraconazole at standard doses (200 mg daily) preceded treatment with amphotericin B, 21 although no advantage was seen when the two drugs were given simultaneously in combination 22 . A previous study in Brazil of daily doses of 4 mg/kg (or up to 400 mg/day) of itraconazole for a period of 6 weeks resulted in the cure of six of 10 cases of MCL 8 .…”
Background A well‐tolerated oral drug is required for the treatment of mucocutaneous leishmaniasis (MCL). Current parenteral treatment regimens with pentavalent antimonials are associated with marked toxicity and significant rates of relapse.
Aim To evaluate the efficacy and tolerability of high‐dose itraconazole for the treatment of MCL.
Methods An uncontrolled treatment study was performed in 13 Ecuadorian patients with MCL. Each patient received a daily dosage of 400 mg of itraconazole for a minimum of 3 months.
Results All 13 subjects responded to itraconazole during the first month of treatment, but by 12 months after treatment the complete resolution of MCL lesions was observed in only three (23%) subjects. No adverse effects of treatment were reported. Response to treatment was associated with a short evolution of the disease and mild to moderate disease severity.
Conclusion Prolonged and high‐dose treatment regimens with itraconazole are not effective for the treatment of the majority of patients with MCL.
“…Amphotericin B and paromomycin increased miltefosine activity in mice infected with L. donovani [70]. A combination of amphotericin B plus itraconazole did not succeed in the treatment of MCL in Peru and Bolivia [71].…”
Leishmaniasis is a protozoan vector borne disease prevalent throughout the world and present in at least 88 countries. The parasite is transmitted by infected phlebotomine sandfly bites. While conventional therapies i.e. pentavalent antimonials, amphotericin B and pentamidine continue to play a major role, it is evident that new drugs or strategies must circumvent the limitations, such as a long-term parenteral administration, toxicity, the high cost in endemic countries and the emergence of resistance, that prevail. One of the most promising drugs is miltefosine, a new oral, approved alkylphospholipid for visceral leishmaniasis with only slight adverse effects. Although we have now this recent and encouraging advance, there is still a need to develop safe, efficient and affordable new treatments for the different clinical forms that exist. This review summarises conventional therapy and the current efforts in the discovery of drugs to treat leishmaniasis with the emphasis on drug combinations to enhance efficiency and prevent the emergence of resistance, the investigation of natural products with the objective of offering new bioactive chemical structures and the development of novel antileishmanial targets.
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