Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia

BackgroundThe diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.ObjectivesTo evaluate the clinical performance of a rapid nanopore-sequencing based metagenomics test for diagnosis of bacterial pathog...

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Main Authors: Shengrui Mu, Long Hu, Ye Zhang, Yingmei Liu, Xiaojing Cui, Xiaohui Zou, Yeming Wang, Binghuai Lu, Shuilian Zhou, Xiaoxue Liang, Chen Liang, Nick Xiao, Justin O’Grady, Shela Lee, Bin Cao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Cellular and Infection Microbiology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2021.684965/full
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author Shengrui Mu
Shengrui Mu
Shengrui Mu
Long Hu
Ye Zhang
Yingmei Liu
Yingmei Liu
Yingmei Liu
Xiaojing Cui
Xiaojing Cui
Xiaojing Cui
Xiaohui Zou
Xiaohui Zou
Xiaohui Zou
Yeming Wang
Yeming Wang
Yeming Wang
Binghuai Lu
Binghuai Lu
Binghuai Lu
Shuilian Zhou
Xiaoxue Liang
Chen Liang
Nick Xiao
Justin O’Grady
Justin O’Grady
Shela Lee
Bin Cao
Bin Cao
Bin Cao
Bin Cao
author_facet Shengrui Mu
Shengrui Mu
Shengrui Mu
Long Hu
Ye Zhang
Yingmei Liu
Yingmei Liu
Yingmei Liu
Xiaojing Cui
Xiaojing Cui
Xiaojing Cui
Xiaohui Zou
Xiaohui Zou
Xiaohui Zou
Yeming Wang
Yeming Wang
Yeming Wang
Binghuai Lu
Binghuai Lu
Binghuai Lu
Shuilian Zhou
Xiaoxue Liang
Chen Liang
Nick Xiao
Justin O’Grady
Justin O’Grady
Shela Lee
Bin Cao
Bin Cao
Bin Cao
Bin Cao
author_sort Shengrui Mu
collection DOAJ
description BackgroundThe diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.ObjectivesTo 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.MethodsWe 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.Results171 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.ConclusionsRapid 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.
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spelling doaj.art-602627378d4046e29c6a903c02023dad2022-12-21T17:17:45ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882021-10-011110.3389/fcimb.2021.684965684965Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial PneumoniaShengrui Mu0Shengrui Mu1Shengrui Mu2Long Hu3Ye Zhang4Yingmei Liu5Yingmei Liu6Yingmei Liu7Xiaojing Cui8Xiaojing Cui9Xiaojing Cui10Xiaohui Zou11Xiaohui Zou12Xiaohui Zou13Yeming Wang14Yeming Wang15Yeming Wang16Binghuai Lu17Binghuai Lu18Binghuai Lu19Shuilian Zhou20Xiaoxue Liang21Chen Liang22Nick Xiao23Justin O’Grady24Justin O’Grady25Shela Lee26Bin Cao27Bin Cao28Bin Cao29Bin Cao30China-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaChina-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaChina-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaNorwich Medical School, University of East Anglia, Norwich, United KingdomQuadram Institute Bioscience, Norwich Research Park, Norwich, United KingdomState Key Laboratory of Translational Medicine and Innovative Drug Development, Simcere Diagnostics Co., Ltd., Nanjing, ChinaChina-Japan Friendship Hospital, National Clinical Research Center for Respiratory Diseases, Clinical Center for Pulmonary Infections, Capital Medical University, Beijing, ChinaInstitute of Respiratory Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center for Respiratory Diseases, China-Japan Friendship Hospital, Beijing, ChinaTsinghua University-Peking University Joint Center for Life Sciences, Tsinghua University, Beijing, ChinaBackgroundThe diagnosis of bacterial pathogens in lower respiratory tract infections (LRI) using conventional culture methods remains challenging and time-consuming.ObjectivesTo 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.MethodsWe 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.Results171 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.ConclusionsRapid 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.https://www.frontiersin.org/articles/10.3389/fcimb.2021.684965/fullnanopore sequencinglower respiratory infectionsrapid diagnosticsbacterial pneumoniapathogenic diagnosis
spellingShingle Shengrui Mu
Shengrui Mu
Shengrui Mu
Long Hu
Ye Zhang
Yingmei Liu
Yingmei Liu
Yingmei Liu
Xiaojing Cui
Xiaojing Cui
Xiaojing Cui
Xiaohui Zou
Xiaohui Zou
Xiaohui Zou
Yeming Wang
Yeming Wang
Yeming Wang
Binghuai Lu
Binghuai Lu
Binghuai Lu
Shuilian Zhou
Xiaoxue Liang
Chen Liang
Nick Xiao
Justin O’Grady
Justin O’Grady
Shela Lee
Bin Cao
Bin Cao
Bin Cao
Bin Cao
Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia
Frontiers in Cellular and Infection Microbiology
nanopore sequencing
lower respiratory infections
rapid diagnostics
bacterial pneumonia
pathogenic diagnosis
title Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia
title_full Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia
title_fullStr Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia
title_full_unstemmed Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia
title_short Prospective Evaluation of a Rapid Clinical Metagenomics Test for Bacterial Pneumonia
title_sort prospective evaluation of a rapid clinical metagenomics test for bacterial pneumonia
topic nanopore sequencing
lower respiratory infections
rapid diagnostics
bacterial pneumonia
pathogenic diagnosis
url https://www.frontiersin.org/articles/10.3389/fcimb.2021.684965/full
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