BACKGROUND Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, and the number of new cases of multidrug resistant TB (MDR-TB), pre extensively drug-resistant TB (pre-XDR-TB) and extensively drug-resistant TB (XDR-TB) has increased considerably worldwide. OBJECTIVES Herein, using 156 M. tuberculosis isolates from 106 patients previously classified as MDR or pre-XDR or XDR isolates, we investigated the genetic mutation profiles associated with phenotypic resistances in patients with MDR-TB, pre-XDR-TB and XDR-TB, treatment outcomes and resistance evolution. METHODS Molecular analyses were performed by partial sequencing of the rpoB, katG, gyrA, gyrB, rrs genes and analysis of the fabG-inhA promoter region. Clinical, epidemiologic and demographic data were obtained from the TB Notification database system of São Paulo (TB-WEB) and the Information System for Special Tuberculosis Treatments (SITE-TB). FINDINGS Drug resistance was attributed to previously known mutations and a novel Asp449Val mutation in gyrB was observed in four isolates from the same patient. Ten patients had more than one isolate evaluated and eight of these patients displayed resistance progression. MAIN CONCLUSIONS The present study is the first to report the frequency of mutations related to second-line drug resistance in MDR-TB, pre-XDR-TB and XDR-TB isolates. The results could lead to the improvement of available technologies for the rapid detection of drug resistant TB.

中文翻译：

---

巴西圣保罗耐药结核分枝杆菌临床分离株中一线和二线耐药相关突变的频率。


背景结核病（TB）是由结核分枝杆菌引起的传染病，耐多药结核病（MDR-TB）、前广泛耐药结核病（前XDR-TB）和广泛耐药结核病的新发病例数结核病（广泛耐药结核病）在全球范围内大幅增加。目的 在此，我们使用来自 106 名先前被分类为 MDR 或 pre-XDR 或 XDR 分离株的 106 名患者的 156 株结核分枝杆菌分离株，研究了与 MDR-TB、pre-XDR-TB 和 XDR-TB 患者表型耐药相关的基因突变谱。 、治疗结果和耐药性演变。方法 通过对 rpoB、katG、gyrA、gyrB、rrs 基因进行部分测序并分析 fabG-inhA 启动子区域来进行分子分析。临床、流行病学和人口统计数据来自圣保罗结核病通报数据库系统（TB-WEB）和特殊结核病治疗信息系统（SITE-TB）。结果 耐药性归因于先前已知的突变，并且在来自同一患者的四个分离株中观察到了 gyrB 中的新 Asp449Val 突变。十名患者接受了不止一种分离株的评估，其中八名患者表现出耐药性进展。主要结论 本研究首次报告了耐多药结核病、广泛耐药结核病前期和广泛耐药结核病菌株中与二线耐药性相关的突变频率。这些结果可能会导致快速检测耐药结核病的现有技术的改进。