基于吡嗪酰胺药物敏感性改善耐多药结核病治疗结局的研究进展

doi:10.3969/j.issn.2095-3755.2014.02.001

摘要/Abstract

摘要： 吡嗪酰胺是结核病短程化疗方案的重要组成药物,在耐多药结核病的治疗中也必不可少。吡嗪酰胺通过活性形式吡嗪酸破坏结核分枝杆菌细胞膜的跨膜质子浓度梯度,干扰能量代谢而实现杀灭结核分枝杆菌的作用,pncA基因和rpsA基因突变是对吡嗪酰胺耐药的主要机制。耐多药结核病患者中对吡嗪酰胺耐药的发生率高(10%～85%),且对吡嗪酰胺耐药的耐多药结核病患者的预后较差;而吡嗪酰胺敏感患者加用氟喹诺酮(FQ)和二线注射类药物(SLIDs)治疗成功率明显提高。因此,可运用分子检测方法快速鉴定出对吡嗪酰胺敏感的耐多药结核病(Z^S-MDR-TB)和对吡嗪酰胺耐药的耐多药结核病(Z^R-MDR-TB),以及菌株对FQ和SLIDs的敏感性;对Z^R-MDR-TB避免使用吡嗪酰胺,并探索以吡嗪酰胺为基础的联合化疗方案以缩短Z^S-MDR-TB患者的疗程。这些方法将有助于提高疗效,节约成本,降低耐多药结核病患者在治疗中的不良反应。

Abstract: Pyrazinamide (PZA) is an important component of the short course chemotherapy scheme for tuberculosis, also essential in the treatment of multidrug-resistant tuberculosis (MDR-TB). PZA affects transmembrane proton concentration gradient of Mycobacterium tuberculosis (Mtb) cell membrane and energy metabolism to kill Mtb in acid environment by its active form, pyrazinoic acid (POA). The mutations of pncA and rpsA genes are the main mechanism of PZA resistance to M.tb. MDR-TB patients have a high prevalence of PZA resistance (10%-85%), resistance to PZA in MDR-TB is associated with poor outcome, while PZA-sensitive patients using fluoroquinolone (FQ) and second-line injectable drugs (SLIDs) will significantly improve the success rate of treatment in MDR-TB. The following measures may potentially improve the curative effect, save the cost, and reduce the side effects of MDR-TB treatment: use molecular tests to rapidly identify PZA-sensitive MDR-TB (Z^S-MDR-TB), PZA-resistant MDR-TB (Z^R-MDR-TB) and susceptibility profile for FQ and SLIDs; avoid the use of PZA in the patient with Z^R-MDR-TB; and explore a combined chemotherapy regimen comprising PZA to shorten the treatment duration of Z^S-MDR-TB.

刘伟, 孙峰, 张文宏, 张颖. 基于吡嗪酰胺药物敏感性改善耐多药结核病治疗结局的研究进展[J]. 结核病与肺部健康杂志, 2014, 3(2): 77-81. doi: 10.3969/j.issn.2095-3755.2014.02.001

LIU Wei,SUN Feng,ZHANG Wen-hong,ZHANG Ying.. Research progress of improving treatment of MDR-TB by identifying pyrazinamide susceptibility[J]. Journal of Tuberculosis and Lung Health, 2014, 3(2): 77-81. doi: 10.3969/j.issn.2095-3755.2014.02.001

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