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Susceptibility to paromomycin in clinical isolates and reference strains of Leishmania species responsible for tegumentary leishmaniasis in Brazil
Acta Tropica ( IF 2.1 ) Pub Date : 2020-12-29 , DOI: 10.1016/j.actatropica.2020.105806
Elizabeth M Coser 1 , Bianca A Ferreira 1 , Edite H Yamashiro-Kanashiro 2 , José Angelo L Lindoso 3 , Adriano C Coelho 1
Affiliation  

Treatment of tegumentary leishmaniasis in Brazil is limited to pentavalent antimonial, amphotericin B and pentamidine. These drugs, administered parenterally, cause several side effects and have a varied clinical response, depending on the species of Leishmania. Urgent expansion of the therapeutic arsenal against the disease is therefore necessary. Paromomycin is an aminoglycoside antibiotic that has already been approved for the treatment of visceral leishmaniasis in Southeast Asia. Here, we provide an in vitro evaluation of the activity of paromomycin in fifteen clinical isolates from patients with tegumentary leishmaniasis at a reference center for the treatment of the disease. Furthermore, the in vitro susceptibility to this drug in reference strains of Leishmania species that are endemic in Brazil has also been evaluated. Among the clinical isolates, nine were typed as Leishmania (Viannia) braziliensis, five as L. (Leishmania) amazonensis and one as L. (V.) guyanensis. Although never exposed to paromomycin, we found variable susceptibility among these isolates and reference strains in promastigotes and intracellular amastigotes, with the drug being more active in the amastigote form of the parasite. This study provides a preclinical dataset that is useful for the evaluation of paromomycin in the treatment of tegumentary leishmaniasis caused by species that are endemic in Brazil.



中文翻译:


导致巴西外皮利什曼病的利什曼原虫临床分离株和参考菌株对巴龙霉素的敏感性



巴西治疗外皮利什曼病仅限于五价锑、两性霉素 B 和喷他脒。这些药物通过肠胃外给药,会引起多种副作用,并根据利什曼原虫的种类而产生不同的临床反应。因此,迫切需要扩大针对该疾病的治疗手段。巴龙霉素是一种氨基糖苷类抗生素,已在东南亚被批准用于治疗内脏利什曼病。在这里,我们对来自皮膜利什曼病患者的 15 种临床分离株中巴龙霉素的活性进行了体外评估,该患者来自治疗该疾病的参考中心。此外,还评估了巴西流行的利什曼原虫参考菌株对该药物的体外敏感性。临床分离株中,9株为巴西利什曼原虫,5株为亚马逊利什曼原虫,1株为L.(V.) Guyanensis 。尽管从未接触过巴龙霉素,但我们发现这些分离株和参考菌株在前鞭毛体和细胞内无鞭毛体中的敏感性存在差异,该药物在寄生虫的无鞭毛体形式中更活跃。这项研究提供了一个临床前数据集,可用于评估巴龙霉素治疗由巴西特有物种引起的皮部利什曼病。

更新日期:2020-12-29
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