Division of Tuberculosis, Department of Disease Control, Ministry of Public Health, Khon Kaen University, Khon Kaen, Thailand.
Department of Microbiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, Research and Diagnostic Center for Emerging Infectious Diseases, Khon Kaen University, Khon Kaen, Thailand.
Int J Tuberc Lung Dis. 2021 Sep 1;25(9):754-760. doi: 10.5588/ijtld.21.0096.
Whole-genome sequencing (WGS) is a promising tool for the detection of drug-resistant TB (DR-TB). To date, there have been few comparisons of diagnostic performance of WGS and phenotypic drug susceptibility testing (DST) in DR-TB. We compared drug resistance-conferring mutations identified by WGS analysis using TB-Profiler and Mykrobe with phenotypic DST profiles based on the Löwenstein-Jensen proportion method using drug-resistant ( = 537) isolates from across Thailand. Based on available phenotypic DST results, diagnostic performance was analysed for resistance against isoniazid, rifampicin, ethambutol (EMB), streptomycin, ethionamide (ETH), kanamycin, capreomycin (CPM), para-aminosalicylic acid, ofloxacin and levofloxacin. High agreement between the two methods was observed for most drugs (>91%), except EMB (57%, 95% CI 53-61) and ETH (70%, 95% CI 66-74). Also, low specificity was observed for EMB (49%, 95% CI 44-54) and ETH (66%, 95% CI 61-71). Sensitivity was high for most drugs (range 83-98%), except CPM (77%, 95% CI 59-88). Low agreement between WGS and phenotypic tests for drug resistance was found for EMB and ETH. The current genomic database is insufficient for the identification of CPM resistance. Challenges remain for routine usage of WGS-based DST, especially for second-line anti-TB drugs.
全基因组测序（WGS）是检测耐多药结核病（DR-TB）的一种很有前途的工具。迄今为止，WGS 与表型药敏试验（DST）在 DR-TB 中的诊断性能比较很少。我们比较了使用 TB-Profiler 和 Mykrobe 进行 WGS 分析确定的耐药突变与基于 Löwenstein-Jensen 比例法的表型 DST 图谱，该图谱基于来自泰国各地的耐药（=537）分离株。根据现有表型 DST 结果，分析了对异烟肼、利福平、乙胺丁醇（EMB）、链霉素、乙硫异烟胺（ETH）、卡那霉素、卷曲霉素（CPM）、对氨基水杨酸、氧氟沙星和左氧氟沙星的耐药性。除 EMB（57%，95%CI53-61）和 ETH（70%，95%CI66-74）外，两种方法对大多数药物的一致性都很高（>91%）。此外，EMB（49%，95%CI44-54）和 ETH（66%，95%CI61-71）的特异性较低。大多数药物的敏感性较高（范围 83-98%），除了 CPM（77%，95%CI59-88）。WGS 与表型试验对 EMB 和 ETH 的耐药性的一致性较低。目前的基因组数据库不足以识别 CPM 耐药性。基于 WGS 的 DST 的常规使用仍然存在挑战，特别是对于二线抗结核药物。
