Evaluation of itraconazole monotherapy versus its combination with a single dose of pentamidine for treating cutaneous leishmaniasis caused by Leishmania (Viannia) guyanensis in Amazonas state, western Brazilian Amazon.

Abstract

Background: Cutaneous leishmaniasis has long been a neglected tropical disease mainly due to therapy limitations. The search for safe and effective alternative treatments, particularly oral medications, has led to the development of second-line treatments, such as azole antifungals, including itraconazole. This study aimed to evaluate and compare the therapeutic effectiveness of itraconazole alone and in combination with pentamidine in patients with cutaneous leishmaniasis, caused by Leishmania Viannia guyanensis.

Methods: A randomised clinical trial was conducted at the leishmaniasis outpatient clinic of the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado in Manaus, Amazonas. Ninety eligible patients diagnosed with cutaneous leishmaniasis were selected and randomly assigned to three treatment groups. Control group-Group 1 (G1) received pentamidine isethionate; experimental group-Group 2 (G2) received itraconazole monotherapy; and experimental group-Group 3 (G3) received a combination of itraconazole and one dose of pentamidine isethionate, in standardised doses. Patients were monitored at 30, 60, 90 and 180 days after the completion of treatment. Leishmania species were identified using biomolecular methods.

Results: The patients were predominantly males (84.4%), with a mean age of 40.5 ± 12.9 years. 93% of cases originated from the peripheral areas of Manaus, Amazonas. The average duration of skin lesion evolution was 30 days, with 84% presenting as ulcerated lesions. A single lesion was observed in 57% of cases, 41% measured 2 to 3 cm², and were predominantly on the lower limbs. Four species of Leishmania were identified, with L. guyanensis causing 90% of cases, L. brasiliensis causing 6% of cases, L. amazonensis causing 2.5% of cases and L. naiffi causing 1.2% of cases. Among 72 cases of L. (V.) guyanensis, cure rates were 96% with itraconazole + pentamidine, 83% with itraconazole alone and 58% with pentamidine alone. No serious adverse events were observed in terms of toxicity and tolerability. Injection site pain or induration was the most common adverse effect in G1. In terms of efficacy, patients in G2 and G3 experienced more favourable outcomes, with 90-day cure rates of 56% (G1), 73% (G2) and 90% (G3).

Conclusion: After 90 days, the itraconazole-pentamidine combination therapy was more effective (90%) than either itraconazole or pentamidine alone against cutaneous leishmaniasis in Amazonas state caused by L. guyanensis.