布氏罗得西亚锥虫临床分离株对DL-α-二氟甲基鸟氨酸的敏感性差异
Differential susceptibility to DL-alpha-difluoromethylornithine in clinical isolates of Trypanosoma brucei rhodesiense.
作者信息
Bacchi C J, Nathan H C, Livingston T, Valladares G, Saric M, Sayer P D, Njogu A R, Clarkson A B
机构信息
Haskins Laboratories, Pace University, New York, New York 10038.
出版信息
Antimicrob Agents Chemother. 1990 Jun;34(6):1183-8. doi: 10.1128/AAC.34.6.1183.
Abstract
DL-alpha-Difluoromethylornithine is an enzyme-activated inhibitor of ornithine decarboxylase and an antagonist of polyamine metabolism that has been successful in clinical trials against West African sleeping sickness caused by Trypanosoma brucei gambiense. Its potential for use against the more virulent East African form of the disease, caused by T. brucei rhodesiense, is not certain. We examined 14 East African clinical isolates from the Kenya Trypanosomiasis Research Institute strain bank plus 2 established isolates for susceptibility to DL-alpha-difluoromethylornithine and to standard trypanocides. Seven of 16 strains were partially or totally refractory to DL-alpha-difluoromethylornithine in our test system. Four strains were also refractory to arsenical drugs, and five were refractory to diamidines. The results indicate that other novel agents or combinations of established agents may be needed for chemotherapy of East African disease.
摘要
DL-α-二氟甲基鸟氨酸是鸟氨酸脱羧酶的一种酶激活抑制剂，也是多胺代谢的拮抗剂，已成功用于治疗由布氏冈比亚锥虫引起的西非昏睡病的临床试验。其用于治疗由布氏罗德西亚锥虫引起的毒性更强的东非型疾病的潜力尚不确定。我们检测了来自肯尼亚锥虫病研究所菌株库的14株东非临床分离株以及2株已确定的分离株对DL-α-二氟甲基鸟氨酸和标准杀锥虫剂的敏感性。在我们的测试系统中，16株菌株中有7株对DL-α-二氟甲基鸟氨酸部分或完全耐药。4株菌株对砷剂也耐药，5株对双脒类耐药。结果表明，治疗东非型疾病可能需要其他新型药物或现有药物的联合使用。
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