Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam.
Antimicrob Agents Chemother. 2013 Aug;57(8):3620-7. doi: 10.1128/AAC.00077-13. Epub 2013 May 20.
Isoniazid resistance is highly prevalent in Vietnam. We investigated the molecular and epidemiological characteristics and the association with first-line treatment outcomes of the main isoniazid resistance mutations in Mycobacterium tuberculosis in codon 315 of the katG and in the promoter region of the inhA gene. Mycobacterium tuberculosis strains with phenotypic resistance to isoniazid from consecutively diagnosed smear-positive tuberculosis patients in rural Vietnam were subjected to Genotype MTBDRplus testing to identify katG and inhA mutations. Treatment failure and relapse were determined by sputum culture. In total, 227 of 251 isoniazid-resistant strains (90.4%) had detectable mutations: 75.3% in katG codon 315 (katG315) and 28.2% in the inhA promoter region. katG315 mutations were significantly associated with pretreatment resistance to streptomycin, rifampin, and ethambutol but not with the Beijing genotype and predicted both unfavorable treatment outcome (treatment failure or death) and relapse; inhA promoter region mutations were only associated with resistance to streptomycin and relapse. In tuberculosis patients, M. tuberculosis katG315 mutations but not inhA mutations are associated with unfavorable treatment outcome. inhA mutations do, however, increase the risk of relapse, at least with treatment regimens that contain only isoniazid and ethambutol in the continuation phase.
异烟肼耐药在越南非常普遍。我们研究了主要异烟肼耐药突变在 katG 密码子 315 和 inhA 基因启动子区域与结核分枝杆菌的分子和流行病学特征以及与一线治疗结果的关联。对来自越南农村连续诊断为痰涂片阳性肺结核患者的具有表型异烟肼耐药的结核分枝杆菌菌株进行 Genotype MTBDRplus 检测以鉴定 katG 和 inhA 突变。通过痰培养确定治疗失败和复发。总共，251 株异烟肼耐药菌株中有 227 株（90.4%）可检测到突变：katG 密码子 315 中的 75.3%（katG315）和 inhA 启动子区域中的 28.2%。katG315 突变与预处理对链霉素、利福平、乙胺丁醇的耐药性显著相关，但与北京基因型无关，并且预测了不良治疗结果（治疗失败或死亡）和复发；inhA 启动子区域突变仅与对链霉素的耐药性和复发相关。在肺结核患者中，结核分枝杆菌 katG315 突变而不是 inhA 突变与不良治疗结果相关。然而，inhA 突变确实会增加复发的风险，至少在含有异烟肼和乙胺丁醇的继续期治疗方案中。
