Successful Treatment of New World Cutaneous Leishmaniasis with a Combination of Topical Paromomycin/Methylbenzethonium Chloride and Injectable Meglumine Antimonate

Abstract

Colombian patients with New World cutaneous leishmaniasis were treated with a combination of a topical formulation (15% paromomycin sulfate/5% methylbenzethonium chloride, twice a day) and parenteral meglumine antimonate (20 mg of antimony [Sb]/kg.d]). Cohort 1 received topical therapy for 10 days and Sb for 7 days; 18 (90%) of the 20 patients were cured (follow-up, 12 months). Other clinical data suggested that neither the topical formulation alone nor the 7-day regimen of Sb alone would have cured many patients. In a subsequent cohort, which received topical therapy for 10 days and Sb for 3 days, the cure rate was 42% (eight of 19 patients). In Colombian cohorts (historical controls) treated with Sb alone for 10-15 days, the cure rate was 31%-36%. Side effects in cohort 1 patients consisted of local reactions to the topical formulation: burning and pruritus in 25% of patients and vesicle formation in 15% of patients. This is the first report that a regimen partially composed of topical antimicrobial agents can be highly effective for treatment of New World cutaneous leishmaniasis.

Treatment failure in children in a randomized clinical trial with 10 and 20 days of meglumine antimonate for cutaneous leishmaniasis due to Leishmania viannia species.

“…6 On the other hand, the unexpectedly low response to the recommended dose and duration of therapy using pentavalent antimonials in our study merits special attention. Published efficacy trials of pentavalent antimonial drugs using a regimen of 20 mg Sb/kg/d for 20 days in Colombia and the Americas, have documented an efficacy of 88 to 100% for the treatment of cutaneous leishmaniasis caused by species of the Leishmania Viannia subgenus.…”

“…However, Soto and others cited a report of historical data indicating a 31% efficacy in northwest Colombia. 6 The present investigation sought to determine whether 10 days of treatment with 20 mg Sb/kg/d had an efficacy comparable to that of 20 days with the same dosage (i.e., no greater than 25% reduction in efficacy) for the supervised treatment of patients infected in endemic areas for cutaneous leishmaniasis where L. (V.) panamensis is the predominant species. In order to address this question taking into consideration the patient profile of endemic areas, women and children were included in the trial and supervised treatment was achieved with the participation and training of health volunteers recruited from the affected communities.…”

Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala.

“…The therapeutic effect was measured either against a placebo group 6-8 or a quasiplacebo group (i.e., without treatment 12 ) or against a group treated with meglumine antimonate. 13,18 There was a wide variation in the study protocols used, in the determination of cure rates, and in the pathogenicity of the Leishmania parasites, so a comparison of the therapeutic efficacy is difficult. However, the following pattern seems to emerge: urea (10%) in addition to PR seems to have little or no therapeutic efficacy.…”

Challenges and new discoveries in the treatment of leishmaniasis

“…These results showed that the topical agent by itself would not be appreciably effective in Colombia but that the combination of the topical agent and a weeklong course of meglumine was as effective as had been found historically for a standard 20-day course of glucantime. [51][52][53][54] Nevertheless, the usefulness of a topical agent plus a short course of Sb(v) remains to be confirmed in a controlled trial. 13 Because there is an appreciable rate of local reaction to the paromomycin/methylbenzethonium chloride formulation, in that 25% of patients develop a burning sensation and pruritis and 15% develop vesicles, another formulation has been developed in which methylbenzethonium chloride has been replaced by 10% urea.…”