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2006年批准所造成的内脏利什曼病的治疗氨基糖苷类抗生素杜氏利什曼原虫在东南亚。尽管这种药物在巴西未被批准用于治疗内脏和皮肤利什曼病，但迫切和必要地评估这种药物作为治疗这些临床形式疾病的物种的替代品的潜力。在巴西，亚马逊利什曼原虫引起皮肤和弥漫性皮肤利什曼病。该疾病的弥漫性皮肤形式难以治疗并且经常复发，主要是在治疗中断时。在这里，我们评估了巴龙霉素敏感性体外一的亚马逊利什曼原虫从皮肤利什曼病患者和参考菌株L. amazonensis M2269 中分离出的临床分离物，以及其在小鼠实验模型中的体内功效。尽管从未接触过巴龙霉素，但发现这两个品系之间存在显着差异的敏感性。巴龙霉素在体外对两种形式的寄生虫的临床分离株都具有高度活性，而其对参考菌株的活性较低。对感染这些品系中的每一种的小鼠进行的体内研究表明，巴龙霉素可减少病灶大小和寄生虫负担，并且体外易感性与该药物的有效性之间存在直接相关性体内发现。我们的研究结果表明巴龙霉素的体内功效取决于寄生虫的内在易感性。除此之外，这项研究有助于评估巴龙霉素在巴西由亚马逊乳杆菌引起的皮肤利什曼病的化疗中的潜在用途。