Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China.
Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China; State Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, Shanghai, 200438, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200040, China; Key Laboratory of Medical Molecular Virology (MOE/MOH) and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Int J Infect Dis. 2020 Jul;96:68-72. doi: 10.1016/j.ijid.2020.04.043. Epub 2020 Apr 24.
Whole-genome sequencing (WGS) has been proposed to be a powerful tool to predict drug resistance for antitubercular drugs. However, the feasibility of WGS in predicting final treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) patients remains unclear PATIENTS AND METHODS: In this prospective observational study conducted from January 2014 to September 2016, MDR-TB patients were enrolled consecutively. Genotypic drug sensitivity testing was performed via WGS using culture isolates. Patients were followed for two years to determine the treatment outcomes. Multivariate analysis was used to identify the association between information provided by WGS and the final treatment outcomes RESULTS: A total of 123 patients with MDR-TB were included in this study. The overall favorable treatment outcome rate was 60.2%. Multivariate analysis showed that independent risk factors associated with unfavorable treatment outcome including high-level moxifloxacin phenotypic resistance (OR, 4.362; 95%CI, 1.364-13.950; p=0.013), cycloserine phenotypic resistance (OR, 7.457; 95%CI, 1.644-33.819; p=0.009), mutations causing high-level fluoroquinolones resistance (OR, 3.947; 95%CI, 1.195-13.034; p=0.024), and ethA mutation (OR, 3.817; 95% CI, 1.154-12.823; p=0.028). WGS costs for each patient are ¥450 ($63), and the average turnaround time was one week CONCLUSIONS: In summary, WGS showed promising feasibility in predicting treatment outcomes for MDR-TB patients within a clinically relevant time frame.
全基因组测序（WGS）被提议作为一种预测抗结核药物耐药性的有力工具。然而，WGS 预测耐多药结核病（MDR-TB）患者最终治疗结果的可行性尚不清楚。
在这项于 2014 年 1 月至 2016 年 9 月进行的前瞻性观察性研究中，连续纳入 MDR-TB 患者。使用培养物分离物通过 WGS 进行基因型药物敏感性测试。对患者进行了两年的随访，以确定治疗结果。使用多变量分析来确定 WGS 提供的信息与最终治疗结果之间的关联。
本研究共纳入 123 例 MDR-TB 患者。总体良好治疗结局率为 60.2%。多变量分析显示，与不良治疗结局相关的独立危险因素包括高水平莫西沙星表型耐药（OR，4.362；95%CI，1.364-13.950；p=0.013）、环丝氨酸表型耐药（OR，7.457；95%CI，1.644-33.819；p=0.009）、引起高水平氟喹诺酮类耐药的突变（OR，3.947；95%CI，1.195-13.034；p=0.024）和 ethA 突变（OR，3.817；95%CI，1.154-12.823；p=0.028）。每个患者的 WGS 费用为 450 元（63 美元），平均周转时间为一周。
综上所述，WGS 显示出在临床相关时间范围内预测 MDR-TB 患者治疗结果的有前途的可行性。
