Prospective evaluation of a rapid clinical metagenomics test for bacterial pneumonia

Mu, Shengrui, Hu, Long, Zhang, Ye, Liu, Yingmei, Cui, Xiaojing, Zou, Xiaohui, Wang, Yeming, Lu, Binghuai, Zhou, Shuilian, Liang, Xiaoxue, Liang, Chen, Xiao, Nick, O’Grady, Justin, Lee, Shela and Cao, Bin (2021) Prospective evaluation of a rapid clinical metagenomics test for bacterial pneumonia. Frontiers in Cellular and Infection Microbiology, 11. ISSN 2235-2988

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Background: The diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.  Objectives: To evaluate the clinical performance of a rapid nanopore-sequencing based metagenomics test for diagnosis of bacterial pathogens in common LRIs through a large-scale prospective study.  Methods: We enrolled 292 hospitalized patients suspected to have LRIs between November 2018 and June 2019 in a single-center, prospective cohort study. Rapid clinical metagenomics test was performed on-site, and the results were compared with those of routine microbiology tests.  Results: 171 bronchoalveolar lavage fluid (BAL) and 121 sputum samples were collected from patients with six kinds of LRIs. The turnaround time (from sample registration to result) for the rapid metagenomics test was 6.4 ± 1.4 hours, compared to 94.8 ± 34.9 hours for routine culture. Compared with culture and real-time PCR validation tests, rapid metagenomics achieved 96.6% sensitivity and 88.0% specificity and identified pathogens in 63 out of 161 (39.1%) culture-negative samples. Correlation between enriched anaerobes and lung abscess was observed by Gene Set Enrichment Analysis. Moreover, 38 anaerobic species failed in culture was identified by metagenomics sequencing. The hypothetical impact of metagenomics test proposed antibiotic de-escalation in 34 patients compared to 1 using routine culture.  Conclusions: Rapid clinical metagenomics test improved pathogen detection yield in the diagnosis of LRI. Empirical antimicrobial therapy could be de-escalated if rapid metagenomics test results were hypothetically applied to clinical management.

Item Type: Article
Additional Information: Funding Information: Funding provided by Ministry of Science and Technology (2018YFC1200102 and 2018YFE0102100), the CAMS Innovation Fund for Medical Sciences (CIFMS 2018-I2M-1-003), the UK-China Collaboration Fund to tackle AMR (Innovate UK (TS/S00887X/1), the Fundamental Research Funds for the Central Universities and Research projects on biomedical transformation of China-Japan Friendship Hospital (PYBZ1820) and the Ministry of Science and Technology of China (2017ZX10103004), the Biotechnology and Biological Sciences Research Council (BBSRC) Institute Strategic Programme Microbes in the Food Chain BB/R012504/1 and its constituent projects BBS/E/F/000PR10348 and BBS/E/F/000PR10349 (JO’G). Acknowledgement: The authors thank for SisiDu, JiuyangXu, Fei Zhou, Lin Li, Xiangzhi Liang, Jian Ma, Haobo Tu for helpful discussions and technical support.
Uncontrolled Keywords: bacterial pneumonia,lower respiratory infections,nanopore sequencing,pathogenic diagnosis,rapid diagnostics,microbiology,immunology,microbiology (medical),infectious diseases ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 19 Nov 2021 01:39
Last Modified: 22 Oct 2022 16:30
DOI: 10.3389/fcimb.2021.684965


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