The clinical relevance of Mycobacterial pharmacogenetics
The clinical relevance of Mycobacterial pharmacogenetics
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DOI：
10.1016/j.tube.2009.03.001
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发表时间：
2009-05-01
期刊：
影响因子：
3.2
通讯作者：
van Helden, P. D.
中科院分区：
文献类型：
--
作者：
Warren, R. M.;Streicher, E. M.;van Helden, P. D.
目前的抗结核（抗TB）药物敏感性测试方法提供了一个二分法的读数：分离株报告为药物敏感或耐药。本报告表明，快速分子方法可以提供有关耐药水平和交叉耐药的其他抗结核药物，这是重要的最佳临床管理的信息。海恩基因型（R）MTBDRplus检测检测，最近由世界卫生组织（WHO）批准用于快速结核病诊断和耐药性检测，可以告知是否包括高剂量异烟肼（INH）治疗时，INH单耐药结核病，耐多药结核病或广泛耐药结核病患者的决定。inhA基因或启动子区域中突变的存在通常赋予低水平的INH抗性，其可以被高剂量INK克服。相同的突变也赋予对乙硫异烟胺的抗性，表明在这种情况下将其包括在二线治疗方案中几乎没有益处。这一信息具有高度的临床相关性，因为inhA突变占INH耐药性的很大比例，优化的治疗方案对于改善患者结局和减少耐药TB的传播至关重要。这一假设需要在对照良好的临床和药代动力学研究中进行检验。(C)2009爱思唯尔有限公司版权所有。
Current anti-tuberculosis (anti-TB) drug sensitivity testing methods provide a dichotomous readout: isolates are reported as either drug susceptible or drug resistant. This report demonstrates that rapid molecular methods may provide information concerning both the level of resistance and cross-resistance to other anti-TB drugs that is important for optimal clinical management. Specific mutations detected by the Hain GenoType (R) MTBDRplus test, recently approved by the World Health Organization (WHO) for rapid TB diagnosis and drug resistance testing, could inform the decision of whether to include high dose isoniazid (INH) when treating patients with INH mono-resistant TB, MDR-TB or XDR-TB. The presence of mutations in the inhA gene or promoter region generally confers low level INH resistance that can be overcome by high dose INK The same mutations also confer resistance to ethionamide indicating little benefit from its inclusion in second line treatment regimens in such cases. This information has high clinical relevance since inhA mutations account for a large proportion of INH resistance, and optimized therapy regimens are crucial to improve patient outcomes and reduce the spread of drug resistant TB. This hypothesis needs to be tested in well controlled clinical and pharmacokinetic studies. (C) 2009 Elsevier Ltd. All rights reserved.