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ABSTRACT & COMMENTARY

Topical Paromomycin for Cutaneous Leishmaniasis

April 1, 2013
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By Dean L. Winslow, MD, FACP, FIDSA, Chairman, Department of Medicine, Santa Clara Valley, Medical Center; Clinical Professor, Stanford University School of Medicine, Associate Editor of Infectious Disease Alert.

Dr. Winslow is a consultant for Siemens Diagnostic.

Synopsis: 375 patients with cutaneous leishmaniasis (CL) were randomized to receiving topical paromomycin (PM) with or without gentamicin (GM) vs. vehicle control. Creams were applied once daily for 20 days. The cure rate for PM+GM was 81%, PM alone 82% and 58% for vehicle control.

Source: Ben Salah A, et al. Topical paromomycin with or without gentamicin for cutaneous leishmaniasis. New Eng J Med 2013;368:524-32.

A randomized vehicle-controlled phase 3 trial of topical PM 15% vs. PM 15% + GM 0.5% vs. vehicle control was conducted in Tunisian patients with CL due to Leishmania major. 375 patients were randomized. Patients had from 1-5 lesions each. Lesions were treated daily for 20 days. Cure was defined as at least 50% reduction in size of the index lesion by day 42 and complete re-epithelialization by 98 days and absence of relapse by 168 days. Cure of the index lesion was 81% in the PM-GM group, 82% in the PM-only group, and 58% for the vehicle control. Mild-moderate application site reactions (erythema) were more frequent in the active PM groups than in the vehicle control but did not require treatment discontinuation. No evidence of systemic aminoglycoside toxicity was observed.

Commentary

Cutaneous leishmaniasis is a common clinical problem in North Africa and the Middle East. In fact, one of my colleagues who did his medical training in Iran told me that infection with CL is almost universal in children from this part of the world who grow up outside of urban areas. However it is almost always a self-limited infection, is generally not treated, but can leave a scar (which if in an area like the face is of significant cosmetic concern).

The “gold standard” treatment for CL is still pentavalent antimonial compounds such as stibogluconate (Pentostam) given parenterally daily for 20 days. This compound is painful when given IM, is difficult to give IV, and is associated with some toxicity (headache, nausea, myalgias, neutropenia, thrombocytopenia, electrolyte abnormalities, renal and hepatic toxicity). This is what we used to treat most of the U.S. Army 3rd Infantry Division soldiers who acquired this infection in southern Iraq in the spring and summer of 2003 during the early phase of OPERATION Iraqi Freedom and most of these otherwise healthy young men tolerated treatment well. More recently, miltefosine has shown efficacy for CL but this drug is not available in the U.S.

Probably the most effective systemic treatment for CL (as well as mucocutaneous leishmaniasis and visceral leishmaniasis) is liposomal amphotericin B. Very abbreviated courses of liposomal amphotericin B is now the treatment preferred by the U.S. military infectious diseases community for treatment of CL acquired by our troops in Southwest Asia. When I was Commander of the USAF EMEDS in Baghdad during the “surge” a few years ago I personally used short courses of liposomal amphotericin B for the treatment of CL in Coalition forces and in detainees in Iraq with dramatic success. These abbreviated courses are well-tolerated but liposomal amphotericin B remains incredibly expensive and the cost is prohibitive for the treatment of CL in most patients in the developing world. Oral antifungal triazoles (fluconazole) have also shown some limited efficacy in CL due to L. major but many patients in the one randomized trial which showed efficacy were lost to follow up. The antifungal triazoles are also not effective in CL or mucocutaneous leishmaniasis acquired in the Americas.

This study shows that topical paromomycin applied daily for 20 days in patients with cutaneous leishmaniasis due L. major appears to be safe and effective. I am looking forward to the next patient I see with this infection so I can give it a try.