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利用宏基因组下一代测序技术推进下呼吸道感染诊断与管理中的微生物检测

Advancing Microbe Detection for Lower Respiratory Tract Infection Diagnosis and Management with Metagenomic Next-Generation Sequencing.

作者信息

Dong Yulan, Chen Qianqian, Tian Bin, Li Jing, Li Jin, Hu Zhidong

机构信息

Department of Clinical Laboratory, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

出版信息

Infect Drug Resist. 2023 Jan 30;16:677-694. doi: 10.2147/IDR.S387134. eCollection 2023.

DOI:10.2147/IDR.S387134
PMID:36743335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9896973/
Abstract

BACKGROUND

Due to limitations of traditional microbiological methods and the presence of the oropharyngeal normal flora, there are still many pathogens that cause lower respiratory tract infections (LRTIs) cannot be detected. Metagenomic next-generation sequencing (mNGS) has the potential capacity to solve this problem.

METHODS

This retrospective study successively reviewed 77 patients with LRTI and 29 patients without LRTI admitted to Tianjin Medical University General Hospital, China from August 2020 to June 2021. Pathogens in bronchoalveolar lavage fluid (BALF) specimens were detected adopting mNGS and traditional microbiological assays. The diagnostic performance of pathogens was compared between mNGS and BALF culture. The value of mNGS for aetiological and clinical impact investigation in LRTI was also evaluated.

RESULTS

Among 77 patients with LRTI, 22.1%, 40.3%, and 65.0% of cases were detected as definite or probable pathogens by culture, all conventional microbiological tests, and mNGS, respectively. Using the final diagnosis as a gold standard, mNGS exhibited a sensitivity of 76.6% (95% confidence interval [CI], 65.6-85.5%), which was considerably superior to that of BALF culture (76.6% vs 18.2%; < 0.01); specificity of 79.3% (95% CI, 60.3-92.0%), which was similar (79.3% vs 89.7%; = 0.38); positive-predictive value of 90.8% (95% CI, 81.0-96.5%), and negative-predictive value of 56.1% (95% CI, 39.7-71.5%). According to our data, mNGS identified potential microorganisms in 66.7% (42/63) of culture-negative samples. Among 59 patients with pathogens identified by mNGS, conventional microbiological methods confirmed pathogenic infections in less than half (28/59) cases. Within the 77 patients, 34 (44.2%) patients received pathogen-directed therapy, 7 (9.1%) patients underwent antibiotic adjustment, and 3 (3.9%) patients stopped using antibiotics due to mNGS results.

CONCLUSION

mNGS exhibits high accuracy in diagnosing LRTI, and combine with traditional microbiological tests, causative pathogens can be detected in approximately 70.0% of cases, thus yields a positive effect on antibiotic application.

摘要

背景

由于传统微生物学方法的局限性以及口咽正常菌群的存在,仍有许多引起下呼吸道感染(LRTIs)的病原体无法被检测到。宏基因组下一代测序(mNGS)有潜力解决这一问题。

方法

这项回顾性研究连续纳入了2020年8月至2021年6月在中国天津医科大学总医院收治的77例LRTI患者和29例无LRTI患者。采用mNGS和传统微生物学检测方法检测支气管肺泡灌洗液(BALF)标本中的病原体。比较mNGS和BALF培养对病原体的诊断性能。还评估了mNGS在LRTI病因学和临床影响调查中的价值。

结果

在77例LRTI患者中,通过培养、所有传统微生物学检测和mNGS分别检测出22.1%、40.3%和65.0%的病例为明确或可能的病原体。以最终诊断作为金标准,mNGS的敏感性为76.6%(95%置信区间[CI],65.6 - 85.5%),显著优于BALF培养(76.6%对18.2%;P < 0.01);特异性为79.3%(95% CI,60.3 - 92.0%),两者相似(79.3%对89.7%;P = 0.38);阳性预测值为90.8%(95% CI,81.0 - 96.5%),阴性预测值为56.1%(95% CI,39.7 - 71.5%)。根据我们的数据,mNGS在66.7%(42/63)的培养阴性样本中鉴定出潜在微生物。在mNGS鉴定出病原体的59例患者中,传统微生物学方法仅在不到一半(28/59)的病例中证实了病原体感染。在77例患者中,34例(44.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/39a7586e0458/IDR-16-677-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/81b7d3a1970e/IDR-16-677-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/918d95ccc722/IDR-16-677-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/f98f7896e4cb/IDR-16-677-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/39a7586e0458/IDR-16-677-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/81b7d3a1970e/IDR-16-677-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/918d95ccc722/IDR-16-677-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/f98f7896e4cb/IDR-16-677-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b82/9896973/39a7586e0458/IDR-16-677-g0004.jpg

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