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巴西引起皮肤利什曼病的利什曼物种临床分离株和参考株对巴龙霉素的敏感性。

Susceptibility to paromomycin in clinical isolates and reference strains of Leishmania species responsible for tegumentary leishmaniasis in Brazil.

机构信息

Departamento de Biologia Animal, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil.

Laboratório de Soroepidemiologia e Imunobiologia, Instituto de Medicina Tropical de São Paulo, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil; Laboratório de Imunologia (LIM 48), Departamento de Moléstias Infecciosas e Parasitárias, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

出版信息

Acta Trop. 2021 Mar;215:105806. doi: 10.1016/j.actatropica.2020.105806. Epub 2020 Dec 29.

DOI:10.1016/j.actatropica.2020.105806
PMID:33385363
Abstract

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.

摘要

巴西的皮肤利什曼病的治疗方法仅限于五价锑、两性霉素 B 和喷他脒。这些药物通过注射给药,会引起多种副作用,并具有不同的临床反应,具体取决于利什曼原虫的种类。因此,急需扩大针对该疾病的治疗武器库。巴龙霉素是一种氨基糖苷类抗生素,已在东南亚获得批准用于治疗内脏利什曼病。在这里,我们在一个治疗该疾病的参考中心,对来自皮肤利什曼病患者的十五株临床分离株进行了巴龙霉素的体外活性评估。此外,还评估了该药物对巴西流行的利什曼原虫参考株的体外敏感性。在临床分离株中,有 9 株被鉴定为巴西利什曼原虫(Viannia),5 株为 L.(Leishmania)亚马逊ensis,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株的原虫和内阿米巴虫的敏感性存在差异,该药物在寄生虫的内阿米巴虫形式中更具活性。本研究提供了一个临床前数据集,可用于评估巴龙霉素治疗巴西流行的利什曼原虫引起的皮肤利什曼病的疗效。

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