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A randomized, placebo-controlled trial of a two-week regimen of aminosidine (paromomycin) ointment for treatment of cutaneous leishmaniasis in Iran.

The effect of a two-week regimen of topical aminosidine was investigated in a randomized, double-blind, placebo-controlled trial of 251 selected Iranian patients with zoonotic cutaneous leishmaniasis. Patients underwent clinical and parasitologic assessment before and 15 (end of therapy), 45, and 105 days after starting the treatment. Aminosidine ointment was safe and well-tolerated, and produced significant reductions in the prevalence of parasitologically positive smears on days 15 and 105 (but not day 45) after treatment compared with placebo. However, there was no clear clinical benefit at any stage after treatment. We conclude that this twice a day two-week regimen of aminosidine was inadequate to accelerate the recovery of most cases of cutaneous leishmaniasis. However, the ointment did show some clear evidence of parasitologic efficacy and should now be studied in longer or more frequent regimens in an effort to prevent parasitologic relapse and thus promote clinical improvement.

Administration, Topical↗

Clinical recovery and limited cure in canine visceral leishmaniasis treated with aminosidine (paromomycin).

Three groups of three, six, and 12 dogs with parasitologically proven clinical visceral leishmaniasis (Leishmania chagasi infection) were treated with intramuscular aminosidine sulfate at doses of 20 mg/kg/day for 15 days; 80 mg/kg/day for 20 days, and 40 mg/kg/day for 30 days, respectively. Follow-up was by parasitologic examination of bone marrow and skin, serology using the indirect immunofluorescent antibody test, and clinical examination for signs of visceral leishmaniasis or adverse effects of treatment. In animals treated with 20 mg/kg/day, for 15 days, there was dramatic clinical improvement with disappearance of conjunctivitis, increase in appetite, weight gain, and recovery of normal skin condition and a healthy coat, but parasitologic relapse occurred between 50 and 100 days after initiation of treatment. Adverse effects were seen with treatment with 80 mg/kg/day for 20 days; three dogs died during or just after treatment, two showed temporary recovery, and one showed total clinical and parasitologic cure that was maintained for four years. Although adverse effects and relapses were seen in some dogs treated with 40 mg/kg/day for 30 days, three of 12 dogs showed complete parasitologic and clinical cure that was sustained for at least four years. Aminosidine treatment cannot be recommended as an alternative to the humane destruction of dogs for the control of canine visceral leishmaniasis because ineffective treatment may prolong carrier status or encourage development of drug resistance. This drug may be a therapeutic option if there is no danger of a dog acting as a reservoir of infection. Achievement of clinical recovery and limited cure with aminosidine suggests that further trials would be of value, possibly in combination with other anti-leishmanial drugs and with supportive measures to reduce adverse effects.

Animals↗

6"'-Deamino-6"'-hydroxy derivatives, as intermediates in the biosynthesis of neomycin and paromomycin.

From broths of a neomycin producing Streptomyces fradiae and of a mutant of Streptomyces rimosus forma paromomycinus respectively, 6"'-deamino-6"'-hydroxyneomycin and 6"'-deamino-6"'hydroxyparomomycin were obtained and their structures established by mass and 13C-NMR spectroscopy and by the study of hydrolytic fragments. These new compounds, which are both present as two epimers at C-5"', are suggested as intermediates in the biosynthesis of the parent antibiotics. The place and the mechanism of the 5"'-epimerisation and of the 6"'-amination are discussed.

Chemical Phenomena↗

Paromomycin.

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Anti-Bacterial Agents↗