结核分枝杆菌复合体(MTBC)分离株的表型敏感性测试需要培养物生长,这可以延迟抗性病例的快速检测。全基因组测序(WGS)和数据分析管道可以帮助预测对结核病(TB)治疗中使用的抗菌药物的耐药性。这项研究比较了表型敏感性测试结果和基于WGS的抗菌素耐药性(AMR)与四种一线抗生素异烟肼的预测,利福平,乙胺丁醇,和吡嗪酰胺-用于在2018-2022年间测试的MTBC分离株。对于这项为期5年的回顾性分析,WGS预测异烟肼耐药性的敏感性,利福平,乙胺丁醇,使用Mykrobe的吡嗪酰胺占86.7%,100.0%,100.0%,和47.8%,分别,特异性为99.4%,99.5%,98.7%,99.9%,分别。使用TBProfiler应用的Mykrobe校正,预测值略有改善,即,异烟肼的WGS敏感性,利福平,乙胺丁醇,吡嗪酰胺占92.31%,100%,100%,57.78%,分别,特异性为99.63%。99.45%,98.93%,99.93%,分别。利用基于WGS的测试解决了有关测试周转时间的问题,并实现了对MTBC成员识别的分析,抗菌素耐药性预测,混合培养物的检测,和菌株基因分型,全部通过一个实验室测试。与使用WHOTB突变目录的传统表型易感性测试方法相比,WGS能够进行快速耐药性检测。提供对鲜为人知的突变的洞察,当识别高置信度突变时,应将其添加到预测数据库中。基于WGS的方法可以通过确保尽早开始适当的治疗来支持加拿大和全球的结核病消除工作。迅速限制结核病疫情的传播。
Phenotypic susceptibility testing of the Mycobacterium tuberculosis complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid,
rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid,
rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid,
rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.