Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practic
Microbiological Diagnostic Performance of Metagenomic Next-generation Sequencing When Applied to Clinical Practic
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DOI：
10.1093/cid/ciy693
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发表时间：
2018-12-01
影响因子：
11.8
通讯作者：
Hu, Bijie
中科院分区：
文献类型：
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作者：
Miao, Qing;Ma, Yuyan;Hu, Bijie
背景宏基因组下一代测序（mNGS）由于其全面性而被认为有可能取代传统的微生物方法学。然而，临床经验与应用的测试是相对有限的。从2017年4月至2017年12月，采集了511份标本，其回顾性诊断分为感染性疾病（347例[67.9%]）、非感染性疾病（119例[23.3%]）和未知病例（45例[8.8%]）。比较了mNGS和培养对病原体的诊断性能。抗生素暴露对检出率的影响也进行了评估。mNGS诊断感染性疾病的敏感性和特异性分别为50.7%和85.7%，优于细菌培养，尤其是结核分枝杆菌（比值比[OR]，4 [95%置信区间{CI}，1.7-10.8]; P < .01），病毒（仅mNGS; P <0.01）、厌氧菌（OR，无穷大[95%CI，1.71-无穷大0]; P <0.01）和真菌（OR，4.0 [95%CI，1.6-10.3]; P <0.01）。重要的是，对于常规方法不确定的mNGS阳性病例，43例（61%）病例导致诊断修改，41例（58%）病例未被经验性抗生素覆盖。对于确定病毒的病例，通常使用广谱抗生素（14/27），其中27例病例中有10例疑似不适当。有趣的是，在抗生素治疗的情况下，mNGS的敏感性上级优于培养（52.5%比34.2%; P <0.01），但不是没有抗生素治疗。mNGS可以产生病原体鉴定的更高灵敏度，并且受先前抗生素暴露的影响较小，从而成为检测传染病的有前途的技术。
Background. Metagenomic next-generation sequencing (mNGS) was suggested to potentially replace traditional microbiological methodology because of its comprehensiveness. However, clinical experience with application of the test is relatively limited.Methods. From April 2017 to December 2017, 511 specimens were collected, and their retrospective diagnoses were classified into infectious disease (347 [67.9%]), noninfectious disease (119 [23.3%]), and unknown cases (45 [8.8%]). The diagnostic performance of pathogens was compared between mNGS and culture. The effect of antibiotic exposure on detection rate was also assessed.Results. The sensitivity and specificity of mNGS for diagnosing infectious disease were 50.7% and 85.7%, respectively, and these values outperformed those of culture, especially for Mycobacterium tuberculosis (odds ratio [OR], 4 [95% confidence interval {CI}, 1.7-10.8]; P < .01), viruses (mNGS only; P < .01), anaerobes (OR, infinity [95% CI, 1.71-infinity 0]; P < .01) and fungi (OR, 4.0 [95% CI, 1.6-10.3]; P < .01). Importantly, for mNGS-positive cases where the conventional method was inconclusive, 43 (61%) cases led to diagnosis modification, and 41 (58%) cases were not covered by empirical antibiotics. For cases where viruses were identified, broad-spectrum antibiotics were commonly administered (14/27), and 10 of 27 of these cases were suspected to be inappropriate. Interestingly, the sensitivity of mNGS was superior to that of culture (52.5% vs 34.2%; P < .01) in cases with, but not without, antibiotic exposure.Conclusions. mNGS could yield a higher sensitivity for pathogen identification and is less affected by prior antibiotic exposure, thereby emerging as a promising technology for detecting infectious diseases.