Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People's Republic of China.
Department of Clinical Laboratory, Shanghai University of Traditional Chinese Medical Attached Shuguang Hospital, Shanghai, People's Republic of China.
Microbiol Spectr. 2022 Apr 27;10(2):e0251621. doi: 10.1128/spectrum.02516-21. Epub 2022 Mar 21.
Our objective was to evaluate the performance of whole-genome sequencing (WGS) from early positive liquid cultures for predicting Mycobacterium tuberculosis complex (MTBC) drug resistance. Clinical isolates were obtained from tuberculosis patients at Shanghai Pulmonary Hospital (SPH). Antimicrobial susceptibility testing (AST) was performed, and WGS from early Bactec mycobacterial growth indicator tube (MGIT) 960-positive liquid cultures was performed to predict the drug resistance using the TB-Profiler informatics platform. A total of 182 clinical isolates were enrolled in this study. Using phenotypic AST as the gold standard, the overall sensitivity and specificity for WGS were, respectively, 97.1% (89.8 to 99.6%) and 90.4% (83.4 to 95.1%) for rifampin, 91.0% (82.4 to 96.3%) and 95.2% (89.1 to 98.4%) for isoniazid, 100.0% (89.4 to 100.0%) and 87.3% (80.8 to 92.1%) for ethambutol, 96.6% (88.3 to 99.6%) and 61.8% (52.6 to 70.4%) for streptomycin, 86.8% (71.9 to 95.6%) and 95.8% (91.2 to 98.5%) for moxifloxacin, 86.5% (71.2 to 91.5%) and 95.2% (90.3 to 98.0%) for ofloxacin, 100.0% (54.1 to 100.0%) and 67.6% (60.2 to 74.5%) for amikacin, 100.0% (63.1 to 100.0%) and 67.2% (59.7 to 74.2%) for kanamycin, 62.5% (24.5 to 91.5%) and 88.5% (82.8 to 92.8%) for ethionamide, 33.3% (4.3 to 77.7%) and 98.3% (95.1 to 99.7%) for para-aminosalicylic acid, and 0.0% (0.0 to 12.3%) and 100.0% (97.6 to 100.0%) for cycloserine. The concordances of WGS-based AST and phenotypic AST were as follows: rifampin (92.9%), isoniazid (93.4%), ethambutol (89.6%), streptomycin (73.1%), moxifloxacin (94.0%), ofloxacin (93.4%), amikacin (68.7%), kanamycin (68.7%), ethionamide (87.4%), para-aminosalicylic acid (96.2%) and cycloserine (84.6%). We conclude that WGS could be a promising approach to predict MTBC resistance from early positive liquid cultures. In this study, we used whole-genome sequencing (WGS) from early positive liquid (MGIT) cultures instead of solid cultures to predict drug resistance of 182 Mycobacterium tuberculosis complex (MTBC) clinical isolates to predict drug resistance using the TB-Profiler informatics platform. Our study indicates that WGS may be a promising method for predicting MTBC resistance using early positive liquid cultures.
我们的目的是评估全基因组测序（WGS）从早期阳性液体培养物预测结核分枝杆菌复合群（MTBC）药物耐药性的性能。临床分离株来自上海肺科医院（SPH）的肺结核患者。进行了抗微生物药物敏感性测试（AST），并使用 TB-Profiler 信息学平台从早期 Bactec 分枝杆菌生长指示管（MGIT）960 阳性液体培养物中进行 WGS 以预测耐药性。共有 182 例临床分离株纳入本研究。以表型 AST 为金标准，WGS 的总敏感性和特异性分别为利福平 97.1%（89.8 至 99.6%）和 90.4%（83.4 至 95.1%），异烟肼 91.0%（82.4 至 96.3%）和 95.2%（89.1 至 98.4%），乙胺丁醇 100.0%（89.4 至 100.0%）和 87.3%（80.8 至 92.1%），链霉素 96.6%（88.3 至 99.6%）和 61.8%（52.6 至 70.4%）， 莫西沙星 86.8%（71.9 至 95.6%）和 95.8%（91.2 至 98.5%），氧氟沙星 86.5%（71.2 至 91.5%）和 95.2%（90.3 至 98.0%），阿米卡星 100.0%（54.1 至 100.0%）和 67.6%（60.2 至 74.5%），卡那霉素 100.0%（63.1 至 100.0%）和 67.2%（59.7 至 74.2%），乙硫异烟胺 62.5%（24.5 至 91.5%）和 88.5%（82.8 至 92.8%），对氨基水杨酸 33.3%（4.3 至 77.7%）和 98.3%（95.1 至 99.7%），环丝氨酸 0.0%（0.0 至 12.3%）和 100.0%（97.6 至 100.0%）。WGS 基于 AST 和表型 AST 的一致性如下：利福平（92.9%），异烟肼（93.4%），乙胺丁醇（89.6%），链霉素（73.1%），莫西沙星（94.0%），氧氟沙星（93.4%），阿米卡星（68.7%），卡那霉素（68.7%），乙硫异烟胺（87.4%），对氨基水杨酸（96.2%）和环丝氨酸（84.6%）。我们得出结论，WGS 可能是一种有前途的方法，可以从早期阳性液体培养物中预测 MTBC 耐药性。在这项研究中，我们使用早期阳性液体（MGIT）培养物的全基因组测序（WGS）代替固体培养物来预测 182 株结核分枝杆菌复合群（MTBC）临床分离株对预测药物耐药性的耐药性，使用 TB-Profiler 信息学平台。我们的研究表明，WGS 可能是一种有前途的方法，可以使用早期阳性液体培养物预测 MTBC 耐药性。
