Successful topical treatment of murine cutaneous leishmaniasis with a combination of paromomycin (aminosidine) and gentamicin

Cutaneous leishmaniasis is presently treated with 20 days of parenteral the rapy with a frequently toxic drug (antimony). Topical formulations of parom omycin (15%) plus methylbenzethonium chloride (MBCL, 12%) or plus urea (10% ) in soft white paraffin have been tested for Old and New World disease in humans. We compared the efficacy of a new topical formulation, WR 279,396 ( paromomycin [15%] plus gentamicin [0.5%]) to the clinical formulations in t he treatment of cutaneous disease in BALB/c mice. Sixty-day-old lesions wer e treated twice a day for 10 days, and the response to therapy was determin ed over a further 70 days. For ulcers due to Leishmania major or to Leishma nia mexicana, 100% of lesions in the WR 279,396 group healed by day 20 afte r therapy and did not relapse by day 70; 83% of lesions healed without rela pse in the paromomycin-MBCL group. In the paromomycin-urea group, 100% of L . major lesions healed by day 30 but 30% relapsed. For ulcers due to Leishm ania panamensis or Leishmania amazonensis, all lesions treated with WR 179, 396 healed and did not relapse: <50% of lesions treated with paromomycin-MB CL healed by day 30, and all lesions relapsed by day 70. In addition to bri ng active, WR 279,396 was not toxic in this model and appears to have a cos metic effect (promoting hair growth, healing, and limiting the size of the scar).