Berman J D, Chulay J D, Hendricks L D, Oster C N
Am J Trop Med Hyg. 1982 May;31(3 Pt 1):459-65. doi: 10.4269/ajtmh.1982.31.459.
Standard courses of pentavalent antimonials frequently fail to cure cutaneous, mucocutaneous, and visceral leishmaniasis, and characteristically fail to cure diffuse cutaneous disease. We have determined the in vitro sensitivity of clinical isolates of Leishmania to pentavalent antimony to determine if inherent drug resistance of the parasite is responsible for treatment failures in human beings. Intracellular amastigotes resulting from promastigote-initiated infection of human macrophages were exposed to pentavalent antimony for 6 days at 34.5-35 degrees C. Amastigotes from clinically sensitive simple cutaneous lesions exhibited a range of in vitro sensitivity. Four strains were greater than or equal to 90% eliminated and two strains were 70-75% eliminated in vitro by concentrations of antimony (15-20 micrograms Sb/ml), comparable to peak achievable serum levels in humans. Amastigotes from initially clinically resistant simple cutaneous lesions showed a wider range of sensitivities. Five strains were greater than or equal to 90% eliminated, but one strain was only 40% eliminated and another strain was completely insensitive in vitro. The clinically resistant diffuse cutaneous strain was 61% eliminated. The techniques described herein permit determination of the in vitro antimicrobial susceptibility of Leishmania from all major human forms of leishmaniasis. The data from this series indicate that in a minority of initially resistant cases parasite resistance to the drug may be contributing to clinical resistance, and use of non-antimonial drugs might be recommended for future therapy.
标准疗程的五价锑剂常常无法治愈皮肤型、黏膜皮肤型和内脏利什曼病，而且典型地无法治愈弥漫性皮肤疾病。我们已测定利什曼原虫临床分离株对五价锑的体外敏感性，以确定寄生虫固有的耐药性是否是人类治疗失败的原因。将前鞭毛体引发的人巨噬细胞感染所产生的细胞内无鞭毛体在34.5 - 35摄氏度下暴露于五价锑6天。来自临床敏感的单纯皮肤病变的无鞭毛体表现出一定范围的体外敏感性。四种菌株在体外被锑浓度（15 - 20微克锑/毫升）消除的比例大于或等于90%，两种菌株被消除的比例为70 - 75%，该锑浓度与人类可达到的血清峰值水平相当。来自最初临床耐药的单纯皮肤病变的无鞭毛体表现出更广泛的敏感性范围。五种菌株被消除的比例大于或等于90%，但一种菌株仅被消除40%，另一种菌株在体外完全不敏感。临床耐药的弥漫性皮肤菌株被消除61%。本文所述技术可用于测定来自人类所有主要利什曼病形式的利什曼原虫的体外抗菌敏感性。该系列数据表明，在少数最初耐药的病例中，寄生虫对药物的耐药性可能导致临床耐药，未来治疗可能推荐使用非锑剂药物。
