Wang Zhenzhen, Xu Liyang, Guo Tengfei, Li Long, Zhang Qing, Liu Jinwei, Zu Xiangyang, Zhao Zhanqin, Xue Yun
The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang, China.
School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, China.
Front Public Health. 2025 May 23;13:1543647. doi: 10.3389/fpubh.2025.1543647. eCollection 2025.
This study aimed to investigate the prevalence of resistance to first-line anti-tuberculosis (TB) drugs and the molecular mechanisms underlying resistance mutations in patients with culture-positive complex (MTBC). The findings provide a data basis for developing more precise and regionally tailored anti-TB treatment regimens.
From 2015 to 2022, a total of 3,605 strains isolated from 10 designated TB medical institutions in the main urban and county/township areas of Luoyang City, China, were confirmed as MTBC members through polymerase chain reaction (PCR) targeting a specific insertion sequence IS6110. Drug susceptibility testing using the proportional method was performed to analyze resistance patterns to first-line anti-TB drugs, namely, isoniazid (INH), rifampin (RFP), streptomycin (SM), and ethambutol (EMB). Molecular drug susceptibility testing was conducted on resistant strains using multicolor melting curve analysis (MMCA) to determine the mutation mechanisms associated with phenotypic resistance.
Among the 3,605 culture-positive MTBC cases, 79.5% (2,866 cases) were male, 64.9% (2,341 cases) resided in county and township areas, and 64.8% (2,336 cases) were younger than 60 years. The resistance rates for first-line anti-TB drugs, from highest to lowest, were SM (16.5%), INH (15.7%), RFP (9.9%), and EMB (6.4%). The overall TB resistance rates were significantly higher in the main urban areas. During the study period, the proportion of mono-resistance tuberculosis (MR-TB), multidrug-resistant tuberculosis (MDR-TB) and polydrug-resistant tuberculosis (PDR-TB) decreased by 59.2% (12.9-5.3%), 40.3% (12.4-7.4%), and 68.3% (6.9-2.2%), respectively. The predominant resistance patterns for MDR-TB and PDR-TB were MDR4 (INH + RIF + EMB + SM) and PDR2 (INH + SM). The significant molecular mutations observed were 43 for SM resistance (66.2%, 344 cases), 315 for INH resistance (70.6%, 361 cases), 529-533 for RFP resistance (54.0%, 183 cases), and 306 for EMB resistance (56.5%, 108 cases). Resistance in MDR-TB and PDR-TB cases frequently involved combinations of hotspot mutations but was not strictly confined to these sites.
Tuberculosis resistance rates have declined over time, with distinct regional variations in resistance patterns. Significant molecular mutations responsible for drug resistance predominantly involve common hotspot mutations, but they are not limited to these.
本研究旨在调查培养阳性的结核分枝杆菌复合群（MTBC）患者对一线抗结核药物的耐药率以及耐药突变的分子机制。研究结果为制定更精确、更具区域针对性的抗结核治疗方案提供了数据基础。
2015年至2022年期间，从中国洛阳市主要城区及县/乡地区的10家指定结核病医疗机构分离出3605株菌株，通过针对特定插入序列IS6110的聚合酶链反应（PCR）确认为MTBC成员。采用比例法进行药敏试验，分析对一线抗结核药物，即异烟肼（INH）、利福平（RFP）、链霉素（SM）和乙胺丁醇（EMB）的耐药模式。对耐药菌株进行分子药敏试验，采用多色熔解曲线分析（MMCA）确定与表型耐药相关的突变机制。
在3605例培养阳性的MTBC病例中，79.5%（2866例）为男性，64.9%（2341例）居住在县乡地区，64.8%（2336例）年龄小于60岁。一线抗结核药物的耐药率从高到低依次为SM（16.5%）、INH（15.7%）、RFP（9.9%）和EMB（6.4%）。主城区的总体结核病耐药率显著更高。在研究期间，单耐药结核病（MR-TB）、耐多药结核病（MDR-TB）和广泛耐药结核病（PDR-TB）的比例分别下降了59.2%（12.9%-5.3%）、40.3%（12.4%-7.4%）和68.3%（6.9%-2.2%）。MDR-TB和PDR-TB的主要耐药模式分别为MDR4（INH + RIF + EMB + SM）和PDR2（INH + SM）。观察到的显著分子突变中，SM耐药43例（66.2%，344例），INH耐药315例（70.6%，361例），RFP耐药529-533例（54.0%，183例），EMB耐药306例（56.5%，108例）。MDR-TB和PDR-TB病例的耐药通常涉及热点突变的组合，但并不严格局限于这些位点。
结核病耐药率随时间下降，耐药模式存在明显的区域差异。导致耐药的显著分子突变主要涉及常见的热点突变，但不限于这些突变。
