Cavalcante Melissa de Sousa Melo, da Silva Lara Isabelli Oliveira, Ortiz Jessica Vanina, de Morais Rômulo Freire, da Silva E Silva Monica Regina Hosannah, Pennini Silmara Navarro, Dos Santos Amanda Bento, Marques Victoria Rosas, Satiro Talita Silva, de Carvalho Gabriel Vinicius Silva, Couceiro Katia do Nascimento, Pinheiro Thamires Batos, Leturiondo André Luiz, Santos Felipe Jules de Araújo, Lindoso José Ângelo Lauletta, Guerra Maria das Graças Vale Barbosa, Guerra Jorge Augusto de Oliveira
Programa de Pós-graduação em Medicine Tropical, Universidade do Estado do Amazonas/Fundação de Medicina Tropical Doutor Heitor Vieira Dourado, Manaus, Amazonas, Brazil.
Escola Superior de Ciências da Saúde, Universidade do Estado do Amazonas, Manaus, Brazil.
Trop Med Int Health. 2025 Sep;30(9):954-965. doi: 10.1111/tmi.70008. Epub 2025 Jul 11.
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.
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.
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 cm, 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).
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.
长期以来，皮肤利什曼病一直是一种被忽视的热带疾病，主要原因是治疗存在局限性。对安全有效的替代治疗方法的探索，尤其是口服药物，促使了二线治疗药物的研发，如唑类抗真菌药，包括伊曲康唑。本研究旨在评估和比较伊曲康唑单独使用以及与喷他脒联合使用对由圭亚那维安尼亚利什曼原虫引起的皮肤利什曼病患者的治疗效果。
在位于亚马孙州马瑙斯的热带医学基金会海托尔·维埃拉·多拉多医生门诊部的利什曼病门诊进行了一项随机临床试验。选取了90名确诊为皮肤利什曼病的合格患者，并随机分为三个治疗组。对照组——第1组（G1）接受乙磺酸盐喷他脒；实验组——第2组（G2）接受伊曲康唑单药治疗；实验组——第3组（G3）接受伊曲康唑与一剂标准剂量乙磺酸盐喷他脒的联合治疗。在治疗结束后的30、60、90和180天对患者进行监测。使用生物分子方法鉴定利什曼原虫种类。
患者以男性为主（84.4%），平均年龄为40.5±12.9岁。93%的病例来自亚马孙州马瑙斯的周边地区。皮肤病变演变的平均持续时间为30天，84%表现为溃疡性病变。57%的病例观察到单个病变，41%的病变大小为2至3厘米，且主要位于下肢。鉴定出四种利什曼原虫，其中圭亚那利什曼原虫导致90%的病例，巴西利什曼原虫导致6%的病例，亚马逊利什曼原虫导致2.5%的病例，奈菲利什曼原虫导致1.2%的病例。在72例圭亚那利什曼原虫病例中，伊曲康唑+喷他脒的治愈率为96%，伊曲康唑单独使用的治愈率为83%，喷他脒单独使用的治愈率为58%。在毒性和耐受性方面未观察到严重不良事件。注射部位疼痛或硬结是G1组最常见的不良反应。在疗效方面，G2组和G3组患者的治疗效果更佳，90天治愈率分别为56%（G1）、73%（G2）和90%（G3）。
90天后，对于亚马孙州由圭亚那利什曼原虫引起的皮肤利什曼病，伊曲康唑-喷他脒联合治疗（90%）比伊曲康唑或喷他脒单独使用更有效。
