title: Successful topical treatment of murine cutaneous leishmaniasis with a combination of paromomycin (Aminosidine) and gentamicin.
abstract: Cutaneous leishmaniasis is presently treated with 20 days of parenteral therapy with a frequently toxic drug (antimony). Topical formulations of paromomycin (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 the treatment of cutaneous disease in BALB/c mice. Sixty-day-old lesions were treated twice a day for 10 days, and the response to therapy was determined over a further 70 days. For ulcers due to Leishmania major or to Leishmania mexicana, 100% of lesions in the WR 279,396 group healed by day 20 after therapy and did not relapse by day 70; 83% of lesions healed without relapse 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 Leishmania panamensis or Leishmania amazonensis, all lesions treated with WR 279,396 healed and did not relapse; < 50% of lesions treated with paromomycin-MBCL healed by day 30, and all lesions relapsed by day 70. In addition to being active, WR 279,396 was not toxic in this model and appears to have a cosmetic effect (promoting hair growth, healing, and limiting the size of the scar).
authors.affiliation: Department of Biologics Research, Walter Reed Army Institute of Research, Walter Reed Army Medical Center, Washington, D.C. 20307-5100, USA.
authors.forename: M
authors.initials: M
authors.lastname: Grogl
authors.forename: B G
authors.initials: BG
authors.lastname: Schuster
authors.forename: W Y
authors.initials: WY
authors.lastname: Ellis
authors.forename: J D
authors.initials: JD
authors.lastname: Berman
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000981:Antiprotozoal Agents / Q000627:therapeutic use*; D001558:Benzethonium / Q000031:analogs & derivatives / Q000627:therapeutic use; D006224:Cricetinae; D004359:Drug Therapy, Combination / Q000008:administration & dosage / Q000627:therapeutic use*; D005839:Gentamicins / Q000008:administration & dosage / Q000627:therapeutic use*; D007891:Leishmania / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D010303:Paromomycin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome; D014508:Urea / Q000627:therapeutic use
chemical_list: D000981:Antiprotozoal Agents; D005839:Gentamicins; D001558:Benzethonium; D010303:Paromomycin; D014508:Urea; C005106:methylbenzethonium chloride