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.
Int J Parasitol Drugs Drug Resist. 2020 Dec;14:91-98. doi: 10.1016/j.ijpddr.2020.08.001. Epub 2020 Aug 15.
Paromomycin is an aminoglycoside antibiotic approved in 2006 for the treatment of visceral leishmaniasis caused by Leishmania donovani in Southeast Asia. Although this drug is not approved for the treatment of visceral and cutaneous leishmaniasis in Brazil, it is urgent and necessary to evaluate the potential of this drug as alternative for the treatment against species responsible for these clinical forms of the disease. In Brazil, Leishmania amazonensis is responsible for cutaneous and diffuse cutaneous leishmaniasis. The diffuse cutaneous form of the disease is difficult to treat and frequent relapses are reported, mainly when the treatment is interrupted. Here, we evaluated paromomycin susceptibility in vitro of a L. amazonensis clinical isolate from a patient with cutaneous leishmaniasis and the reference strain L. amazonensis M2269, as well as its in vivo efficacy in a murine experimental model. Although never exposed to paromomycin, a significant differential susceptibility between these two lines was found. Paromomycin was highly active in vitro against the clinical isolate in both forms of the parasite, while its activity against the reference strain was less active. In vivo studies in mice infected with each one of these lines demonstrated that paromomycin reduces lesion size and parasite burden and a direct correlation between the susceptibility in vitro and the effectiveness of this drug in vivo was found. Our findings indicate that paromomycin efficacy in vivo is dependent on intrinsic susceptibility of the parasite. Beyond that, this study contributes for the evaluation of the potential use of paromomycin in chemotherapy of cutaneous leishmaniasis in Brazil caused by L. amazonensis.
巴龙霉素是一种氨基糖苷类抗生素，于 2006 年获批用于治疗东南亚由利什曼原虫引起的内脏利什曼病。尽管该药未在巴西获批用于治疗内脏和皮肤利什曼病，但评估该药作为治疗引起这些临床形式疾病的物种的替代药物的潜力是紧迫且必要的。在巴西，莱什曼原虫亚马逊亚种是引起皮肤利什曼病和弥漫性皮肤利什曼病的原因。该疾病的弥漫性皮肤形式难以治疗，且报告称经常复发，主要是在治疗中断时。在这里，我们评估了巴龙霉素对一名皮肤利什曼病患者的临床分离株和参考株莱什曼原虫 M2269 的体外敏感性，以及其在小鼠实验模型中的体内疗效。尽管该临床分离株从未接触过巴龙霉素，但发现这两种菌株之间存在显著的差异敏感性。巴龙霉素对寄生虫的两种形式的临床分离株均具有高度的体外活性，而对参考株的活性则较弱。用这两种菌株感染小鼠的体内研究表明，巴龙霉素可减小病变大小和寄生虫负荷，并发现体外敏感性与该药物在体内的有效性之间存在直接相关性。我们的研究结果表明，巴龙霉素在体内的疗效取决于寄生虫的固有敏感性。除此之外，这项研究有助于评估巴龙霉素在巴西由莱什曼原虫亚马逊亚种引起的皮肤利什曼病化疗中的潜在用途。
