Which medications in the drug class Antifungals, Systemic are used in the treatment of Leishmaniasis?

Updated: Feb 18, 2020
  • Author: Craig G Stark, MD, FACP, FFTM, RCPS(Glasg), FISTM; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Answer

Antifungals, Systemic

Antifungal and antiparasitic medications are used in resistant leishmaniasis in combination with other agents. The mechanisms of action may involve an alteration of RNA and DNA metabolism or an intracellular accumulation of peroxide that is toxic to the fungal cell. The major sterol in Leishmania organisms and fungi is ergosterol. Antiergosterol agents are marketed as antifungals.

When systemic agents are administered, monitor patients for adverse effects and complications common to the drug.

Amphotericin B liposomal (AmBisome)

Traditionally, amphotericin B, produced by a strain of Streptomyces nodosus, is a fungistatic or fungicidal agent that attacks the ergosterol wall of the Leishmania parasite, causing intracellular components to leak with subsequent fungal cell death. Its use has been limited because of its high adverse effect profile, but newer lipophilic formulations that reduce toxicity have shown promise in treating resistant visceral and mucocutaneous disease. These formulations are taken up well by the reticuloendothelial system and poorly by the kidney, decreasing the risk of nephrotoxicity.

Liposomal amphotericin B has become the drug of choice in antimony-resistant infections (especially if contracted in India).

In addition to miltefosine, AmBisome is the only FDA-approved drug for the treatment of visceral leishmaniasis in the United States. This agent is available as a 100 mg/20 mL preparation.

Cure rates of 90% and higher have been observed in various studies, except possibly in patients with HIV infection. A short-course regimen consisting of a single dose of liposomal amphotericin followed by 7-14 days of miltefosine has resulted in cure rates greater than 90% in north India.

The high cost of liposomal amphotericin B is a disadvantage to its use in areas where visceral leishmaniasis is prevalent.

Ketoconazole

Ketoconazole is an imidazole broad-spectrum antifungal agent that inhibits synthesis of ergosterol, causing cellular components to leak and resulting in fungal cell death.

Itraconazole (Sporanox, Onmel)

Itraconazole is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting CYP-450–dependent synthesis of ergosterol, a vital component of fungal cell membranes.


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