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用硫利达嗪(一种细菌外排泵抑制剂)治疗广泛耐药结核病/耐多药结核病的前景疗法。

Promising therapy of XDR-TB/MDR-TB with thioridazine an inhibitor of bacterial efflux pumps.

作者信息

Amaral L, Martins M, Viveiros M, Molnar J, Kristiansen J E

机构信息

Unit of Mycobacteriology, UPMM, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Lisboa, Portugal.

出版信息

Curr Drug Targets. 2008 Sep;9(9):816-9. doi: 10.2174/138945008785747798.

Abstract

Global rates of pulmonary tuberculosis (TB) continue to increase. Moreover, resistance of the causative organism Mycobacterium tuberculosis to the two most effective anti-TB medications continue to rise. Now, multi-drug resistant TB (MDR-TB) has progressed to extensively drug resistant TB (XDR-TB) - a M. tuberculosis organism that is resistant to the most effective second line drugs available for the treatment of TB. This review provides detailed, significant evidence that supports the use of an old neuroleptic compound, thioridazine (TZ), for the management of MDR-TB and XDR-TB infections and which has been shown to inhibit efflux pumps of bacteria. The argument has been previously presented but no one seems to be listening - and the disease continues unabated when there is a very good probability that the suggested drug will prove to be effective. When the prognosis is poor, available therapy predictably ineffective and death is inevitable, compassionate therapy with TZ should be contemplated. The risks are small and the rewards great.

摘要

全球肺结核(TB)发病率持续上升。此外,致病微生物结核分枝杆菌对两种最有效的抗结核药物的耐药性也在不断增加。如今,耐多药结核病(MDR-TB)已发展为广泛耐药结核病(XDR-TB)——一种对治疗结核病可用的最有效二线药物具有耐药性的结核分枝杆菌菌株。本综述提供了详细且重要的证据,支持使用一种古老的抗精神病化合物硫利达嗪(TZ)来治疗耐多药结核病和广泛耐药结核病感染,并且已证明该化合物可抑制细菌的外排泵。此前已有相关观点提出,但似乎无人倾听——而当所建议的药物很有可能被证明有效时,这种疾病仍未得到缓解。当预后不佳、现有治疗方法可预见地无效且死亡不可避免时,应考虑使用硫利达嗪进行姑息治疗。其风险小而回报大。

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