Dermatologic Manifestations of Leishmaniasis Medication

For 50 years, the mainstay of antileishmanial therapy has been pentavalent antimony (sodium stibogluconate or meglumine antimonate).^[14] This was previously used for all forms of the disease; however, recently, liposomal amphotericin B has replaced pentavalent antimony as the drug of choice for visceral disease. Pentavalent antimony is not marketed in the United States, but it can be obtained through the CDC under an Investigational New Drug application for civilian use and is also available at 2 medical centers in the US Department of Defense for military use, also under an Investigational New Drug application. Currently, however, efforts are underway to make this drug more widely available in the United States.

Originally, VioQuest Pharmaceuticals, a New Jersey–based biopharmaceutical company, partnered with the US Army, to receive orphan drug designation from the FDA with an eye toward licensure. Unfortunately, this has not materialized and other avenues are being sought, especially with the FDA's offer of priority review vouchers for the registration of badly needed drugs for certain diseases, such as leishmaniasis.

Cure rates for pentavalent antimony are 90-97% with 1-3 full intravenous treatment courses; however, the drawbacks are considerable. These drugs are expensive and difficult to obtain. They must be delivered parenterally, they have numerous adverse effects, they may have lot-to-lot variability, and they are becoming increasingly less effective because of the emergence of drug-resistant parasites (especially in certain countries such as India). In other parts of the world, intralesional injections have shown promise with less toxicity (although with much lower patient tolerability owing to the pain associated with the intralesional injections).

Alternative treatment regimens with acceptable cure rates are pentamidine, paromomycin, interferon-gamma plus antimony, and amphotericin B (and less toxic variations, eg, liposomal amphotericin B, amphotericin B lipid complex, and amphotericin B colloidal dispersion). However, few of these options are used in the United States, except for on antimony-resistant organisms. While much has been made of the use of azoles for the Iraqi L major cutaneous disease, few practitioners in the field believe this is a prudent consideration for routine treatment of this disease. Recently, liposomal amphotericin B has been used with good success in the treatment of cutaneous disease from many parts of the world and is gaining increased acceptance with many practitioners.

Class Summary

These are generally considered first-line therapy for cutaneous and mucocutaneous disease.

Sodium antimony gluconate (Pentostam)

DOC for leishmaniasis in United States. Manufactured by GlaxoSmithKline, London. No fixed chemical formulation; lot-to-lot variability. Storage optimal in dark at 4°C. Poorly understood antileishmanial mechanisms. Drug resistance well documented. Can be delivered locally into cutaneous lesions.

Class Summary

The major sterol in both Leishmania organisms and fungi is ergosterol. Antiergosterol agents, marketed as antifungals, have activity against Leishmania organisms.

Amphotericin B (Fungizone, Amphocin, Amphocil, Abelcet, AmBisome)

DOC in antimony-resistant infections (especially if contracted in India). To reduce renal toxicity (with deoxycholate), several formulations (lipid associated) are used (liposomal [AmBisome], lipid-complexed [Abelcet], colloidal-dispersion [Amphocil] preparations). Least toxic (infusion-related adverse effects) is AmBisome; most toxic, Amphocil. All expensive, but cure rates near 100%, except possibly in patients with HIV infection. AmBisome may be most studied lipid-associated preparation but not proven superior to other forms, including non–lipid-associated form.

Pentamidine (Pentam-300, Pentacarinat, NebuPent)

Inhibits growth of protozoa by blocking oxidative phosphorylation and incorporation of nucleic acids into RNA and DNA, inhibiting protein and phospholipid synthesis. Formulated as a sterile powder; must be reconstituted and administered as slow IV infusion or via IM route. Resistance common in India; high relapse rates reported.

Class Summary

Paromomycin has a relatively favorable adverse effect profile, but it is not as effective as antimony or amphotericin B for visceral disease when used as monotherapy. Paromomycin can be used in combination with sodium antimony gluconate to reduce the total time of therapy, and it has better cure rates.

Paromomycin (Aminosidine)

Amebicidal and antibacterial aminoglycoside obtained from Streptomyces rimosus grain; active in intestinal amebiasis. Recommended for treatment of Diphyllobothrium latum, Taenia saginata, Taenia solium, Dipylidium caninum, and Hymenolepis nana infections.

Class Summary

Interferon-gamma a T-helper subtype 1 cytokine used to enhance host immunity to Leishmania parasites.

Interferon-gamma-1b (Actimmune)

Recombinant DNA product. Administered with sodium antimony gluconate (probably ineffective alone).