Shanghai Clinical Research Center for Infectious Disease (Tuberculosis), Department of Tuberculosis and Shanghai Key Lab of Tuberculosis, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, Shanghai, 200433, China.
Tuberculosis Prevention Division, Shanghai Center for Disease Control and Prevention, Shanghai, China.
BMC Infect Dis. 2022 May 27;22(1):499. doi: 10.1186/s12879-022-07482-4.
Our aim was to assess the ability of the Whole-genome sequencing (WGS) in predicting drug resistance profile of multidrug-resistant mycobacterium tuberculosis (MDR-MTB) from newly diagnosed cases in China.
We validated the Phenotypic drug Sensitivity Test (pDST) for 12 anti-tuberculosis drugs using the Bactec MGIT 960 system. We described the characteristics of the isolates enrolled and compared the pDST results with resistance profiles predicted by WGS.
The pDST showed that of the 43 isolates enrolled, 25.6% were sensitive to rifabutin (RFB); 97.7%、97.7%、93.0% and 93.0% were sensitive to cycloserine (Cs), amikacin/kanamycin (Ak/Km), para-aminosalicylic acid (Pas) and ethionamide Eto), respectively; 18.6% were resistant to fluoroquinolones (FQs) or second-line injections. Genotype DST determined by WGS of Ak/Km、Eto and RFP reached high consistency to 97.7% compared with pDST, followed by moxifloxacin (Mfx) 95.3%, levofloxaci (Lfx) and Pas 93%, streptomycin (Sm) 90.3%. The genotype DST of RFB and EMB showed low consistency with the pDST of 67.2 and 79.1%. WGS also detected 27.9% isolates of pyrazinamide(PZA)-related drug-resistant mutation. No mutations associated with linezolid (Lzd), bedaquiline (Bdq) and clofazimine (Cfz) were detectd.
WGS has the potential to infer resistance profiles without time-consuming phenotypic methods, which could be provide a basis to formulate reasonable treatment in high TB burden areas.
本研究旨在评估全基因组测序（WGS）在预测中国新诊断耐多药结核分枝杆菌（MDR-MTB）药物耐药谱方面的能力。
我们使用 Bactec MGIT 960 系统验证了 12 种抗结核药物的表型药敏试验（pDST）。我们描述了纳入的分离株的特征，并将 pDST 结果与 WGS 预测的耐药谱进行了比较。
pDST 显示，在纳入的 43 株分离株中，25.6%对利福布丁（RFB）敏感；97.7%、97.7%、93.0%和 93.0%分别对环丝氨酸（Cs）、阿米卡星/卡那霉素（Ak/Km）、对氨基水杨酸（Pas）和乙硫异烟胺（Eto）敏感；18.6%对氟喹诺酮类（FQs）或二线注射剂耐药。WGS 基因型 DST 对 Ak/Km、Eto 和 RFP 的测定与 pDST 具有高度一致性，达到 97.7%，其次是莫西沙星（Mfx）95.3%、左氧氟沙星（Lfx）和 Pas 93%、链霉素（Sm）90.3%。RFB 和 EMB 的基因型 DST 与 pDST 的一致性较低，分别为 67.2%和 79.1%。WGS 还检测到 27.9%的吡嗪酰胺（PZA）相关耐药突变株。未检测到与利奈唑胺（Lzd）、贝达喹啉（Bdq）和氯法齐明（Cfz）相关的突变。
WGS 具有在无需费时的表型方法的情况下推断耐药谱的潜力，可为高结核负担地区制定合理的治疗方案提供依据。
