Baptista Cibele, Miranda Luciana de Freitas Campos, Madeira Maria de Fátima, Leon Leonor Laura Pinto, Conceição-Silva Fátima, Schubach Armando de Oliveira
Núcleo de Biossegurança, Bio-Manguinhos, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
Laboratório de Pesquisa Clínica e Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, 21040-900 Rio de Janeiro, RJ, Brazil.
Dis Markers. 2015;2015:943236. doi: 10.1155/2015/943236. Epub 2015 Jan 31.
This study evaluated the in vitro sensitivity of paired Leishmania braziliensis samples isolated from the same patient before pentavalent antimonial treatment (Sample A) and after treatment failure or cutaneous leishmaniasis reactivation (Sample B) in patients undergoing intralesional administration or injections (5 mgSb(V)/kg/d) of meglumine antimoniate. Fourteen samples from 7 patients were studied. After 24 h of drug exposure, 50% lethal dose (LD50) values for promastigotes ranged from 0.37 mg/mL to 5.86 mg/mL for samples obtained before treatment (A) and 0.89 mg/mL to 7.80 mg/mL for samples obtained after treatment (B). After 48 h, LD50 values ranged from 0.37 mg/mL to 5.75 mg/mL and 0.70 mg/mL to 7.68 mg/mL for A and B samples, respectively. After 48 h, LD50 values for amastigotes ranged from 11.7 to 44.3 μg/mL for A samples and 13.7 to 52.7 μg/mL for B samples. Of 7 patients, 1 discontinued treatment and 6 were cured after retreatment with amphotericin B (4 cases) or meglumine antimoniate (2 cases). Overall the B samples had higher LD50 values than A samples; however the difference was not significant. These results do not support the hypothesis that low-dose and intralesional treatments induce selection of resistant parasites in vitro and suggest that other factors may influence therapeutic outcome in patients with poor response to initial treatment.
本研究评估了在接受五价锑剂（葡甲胺锑酸盐，5mgSb(V)/kg/d）病灶内给药或注射的患者中，从同一患者分离的巴西利什曼原虫配对样本在五价锑治疗前（样本A）以及治疗失败或皮肤利什曼病复发后（样本B）的体外敏感性。研究了来自7名患者的14个样本。药物暴露24小时后，治疗前获得的样本（A）前鞭毛体的半数致死剂量（LD50）值范围为0.37mg/mL至5.86mg/mL，治疗后获得的样本（B）为0.89mg/mL至7.80mg/mL。48小时后，A样本和B样本的LD50值分别为0.37mg/mL至5.75mg/mL和0.70mg/mL至7.68mg/mL。48小时后，无鞭毛体的LD50值，A样本范围为11.7至44.3μg/mL，B样本为13.7至52.7μg/mL。7名患者中，1名停止治疗，6名在接受两性霉素B（4例）或葡甲胺锑酸盐（2例）再治疗后治愈。总体而言，B样本的LD50值高于A样本；然而，差异不显著。这些结果不支持低剂量和病灶内治疗在体外诱导耐药寄生虫选择的假设，并表明其他因素可能影响初始治疗反应不佳患者的治疗结果。
