期刊
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
卷 39, 期 5, 页码 376-380出版社
ELSEVIER
DOI: 10.1016/j.ijantimicag.2012.01.012
关键词
MDR-TB; XDR-TB; TDR-TB; Thioridazine; Cure; Enhanced intracellular killing; Inhibition of efflux pumps
资金
- Fundacao para a Ciencia e a Tecnologia (FCT) of Portugal [EU-FSE/FEDER-PTDC/SAU-FCF/102807/2008]
Thioridazine (TDZ) in combination with antibiotics to which extensively drug-resistant Mycobacterium tuberculosis (XDR-TB) is initially resistant yields a cure. This is due to the fact that TDZ enhances the killing of intracellular M. tuberculosis by non-killing macrophages, inhibits the genetic expression of efflux pumps of M. tuberculosis that extrude antibiotics prior to reaching their intended targets, and inhibits the activity of existing efflux pumps that contribute to the multidrug-resistant phenotype of M. tuberculosis. The combination of these effects of TDZ probably contributes to the successful recent cures of XDR-TB cases when the phenothiazine TDZ is used in combination with antibiotics to which the patient with XDR-TB was initially unresponsive. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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