中国 10 年间耐异烟肼结核病的流行率和分子特征变化。
Change in prevalence and molecular characteristics of isoniazid-resistant tuberculosis over a 10-year period in China.
机构信息
National Clinical Laboratory on Tuberculosis, Beijing Key laboratory on Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, No. 97, Machang, Tongzhou District, Beijing, 101149, China.
Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
出版信息
BMC Infect Dis. 2019 Aug 5;19(1):689. doi: 10.1186/s12879-019-4333-4.
BACKGROUND
Isoniazid (INH) represents the cornerstone for the treatment of cases infected with Mycobacterium tuberculosis (MTB) strains. Several molecular mechanisms have been shown to be the major causes for INH resistance, while the dynamic change of mutations conferring INH resistance among MTB strains during the past decade is still unknown in China.
METHODS
In this study, we carried out a comparative analysis of the INH minimal inhibitory concentration (MIC) distribution, and investigate the dynamic change of molecular characteristics among INH-resistant MTB strains between 2005 and 2015.
RESULTS
The proportion of INH resistance (39.0%, 105/269) in 2015 was significantly higher than in 2005 (30.0%, 82/273; P = 0.03). Among 269 isolates collected in 2015, 76 (28.3%, 76/269) exhibited high-level INH-resistance (MIC≥32 mg/L), which was significantly higher than that in 2005 (20.5%, 56/273, P = 0.04). In addition, a significantly higher percentage of INH-resistant isolates carried inhA promoter mutations in 2015 (26.7%) versus that in 2005 (14.6%, P = 0.04), while no significant difference was observed in the rates of isolates containing katG mutations between 2005 (76.8%) and 2015 (70.5%, P = 0.33). Notably, the proportion of MTB isolates with inhA mutations (26.7%, 28/105) for patients who had previous exposure to protionamide (PTH) was higher than that for patients who had no previous exposure to PTH (21.4%, 6/28).
CONCLUSIONS
In conclusion, our results demonstrated that the proportion of INH-resistant MTB isolates significantly increased during the last decade, which was mainly attributed to an increase of high-level INH-resistant MTB. In addition, prior exposure to PTH may be associated with the increased frequency of INH-resistant tuberculosis strains with inhA mutations in China.
背景
异烟肼（INH）是治疗结核分枝杆菌（MTB）菌株感染的基石。已经证明了几种分子机制是 INH 耐药的主要原因，而在过去十年中，MTB 菌株中导致 INH 耐药的突变的动态变化在中国尚不清楚。
方法
在这项研究中，我们对 INH 最小抑菌浓度（MIC）分布进行了比较分析，并研究了 2005 年至 2015 年间 INH 耐药 MTB 菌株中分子特征的动态变化。
结果
2015 年 INH 耐药率（39.0%，105/269）明显高于 2005 年（30.0%，82/273；P=0.03）。在 2015 年采集的 269 株分离株中，76 株（28.3%，76/269）表现出高水平 INH 耐药性（MIC≥32mg/L），明显高于 2005 年（20.5%，56/273，P=0.04）。此外，2015 年 INH 耐药分离株中 inhA 启动子突变的比例明显高于 2005 年（26.7%比 14.6%，P=0.04），而 2005 年和 2015 年 katG 突变分离株的比例无显著差异（76.8%比 70.5%，P=0.33）。值得注意的是，曾接触过吡嗪酰胺（PTH）的患者中，携带 inhA 突变的 MTB 分离株比例（26.7%，28/105）高于从未接触过 PTH 的患者（21.4%，6/28）。
结论
总之，我们的研究结果表明，过去十年中 INH 耐药 MTB 分离株的比例显著增加，这主要归因于高水平 INH 耐药 MTB 的增加。此外，在中国，PTH 的既往暴露可能与 inhA 突变的 INH 耐药结核菌株的频率增加有关。
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