Stagg H R, Lipman M C, McHugh T D, Jenkins H E
Institute of Global Health, UCL, London, UK.
University College London (UCL) Respiratory, Division of Medicine, UCL, London, UK;, Royal Free London National Health Service Foundation Trust, London, UK.
Int J Tuberc Lung Dis. 2017 Feb 1;21(2):129-139. doi: 10.5588/ijtld.16.0716.
The drug isoniazid (INH) is a key component of global tuberculosis (TB) control programmes. It is estimated, however, that 16.1% of TB disease cases in the former Soviet Union countries and 7.5% of cases outside of these settings have non-multidrug-resistant (MDR) INH resistance. Resistance has been linked to poorer treatment outcomes, post-treatment relapse and death, at least for specific sites of disease. Multiple genetic loci are associated with phenotypic resistance; however, the relationship between genotype and phenotype is complex, and restricts the use of rapid sequencing techniques as part of the diagnostic process to determine the most appropriate treatment regimens for patients. The burden of resistance also influences the usefulness of INH preventive therapy. Despite seven decades of INH use, our knowledge in key areas such as the epidemiology of resistant strains, their clinical consequences, whether tailored treatment regimens are required and the role of INH resistance in fuelling the MDR-TB epidemic is limited. The importance of non-MDR INH resistance needs to be re-evaluated both globally and by national TB control programmes.
药物异烟肼（INH）是全球结核病（TB）控制规划的关键组成部分。然而，据估计，在前苏联国家，16.1%的结核病病例以及在这些地区以外，7.5%的病例存在非耐多药（MDR）的异烟肼耐药情况。至少对于特定疾病部位，耐药已与较差的治疗结果、治疗后复发及死亡相关。多个基因位点与表型耐药相关；然而，基因型与表型之间的关系复杂，限制了将快速测序技术作为诊断过程的一部分来确定患者最合适治疗方案的应用。耐药负担也影响异烟肼预防性治疗的效用。尽管异烟肼已使用了七十年，但我们在诸如耐药菌株的流行病学、其临床后果、是否需要量身定制的治疗方案以及异烟肼耐药在推动耐多药结核病流行中的作用等关键领域的知识仍很有限。非耐多药异烟肼耐药的重要性需要在全球范围内以及由各国结核病控制规划重新评估。
