Top

BMC Infectious Diseases

Published in:

01-12-2021 | Community-Acquired Pneumonia | Research article

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia

Authors: Fei Xie, Zhimei Duan, Weiqi Zeng, Shumei Xie, Mingzhou Xie, Han Fu, Qing Ye, Teng Xu, Lixin Xie

Published in: BMC Infectious Diseases | Issue 1/2021

Abstract

Background

Identifying the causes of community-acquired pneumonia (CAP) is challenging due to the disease’s complex etiology and the limitations of traditional microbiological diagnostic methods. Recent advances in next generation sequencing (NGS)-based metagenomics allow pan-pathogen detection in a single assay, and may have significant advantages over culture-based techniques.

Results

We conducted a cohort study of 159 CAP patients to assess the diagnostic performance of a clinical metagenomics assay and its impact on clinical management and patient outcomes. When compared to other techniques, clinical metagenomics detected more pathogens in more CAP cases, and identified a substantial number of polymicrobial infections. Moreover, metagenomics results led to changes in or confirmation of clinical management in 35 of 59 cases; these 35 cases also had significantly improved patient outcomes.

Conclusions

Clinical metagenomics could be a valuable tool for the diagnosis and treatment of CAP.

Trial registration

Trial registration number with the Chinese Clinical Trial Registry: ChiCTR2100043628.

Available only for authorised users

Polverino, ETorres Marti, A. Community-acquired pneumonia. Minerva Anestesiol. 2011;77:196–211.

Mandell LA, Wunderink RG, Anzueto A, et al. Infectious diseases society of America/American thoracic society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(Suppl 2):S27–72. https://doi.org/10.1086/511159.CrossRefPubMed

Lim WS, Baudouin SV, George RC, et al. BTS guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax. 2009;64(Suppl 3):iii1–55. https://doi.org/10.1136/thx.2009.121434.CrossRefPubMed

Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, et al. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415–27. https://doi.org/10.1056/NEJMoa1500245.CrossRefPubMedPubMedCentral

Torres A, Chalmers JD, Dela Cruz CS, et al. Challenges in severe community-acquired pneumonia: a point-of-view review. Intensive Care Med. 2019;45(2):159–71. https://doi.org/10.1007/s00134-019-05519-y.CrossRefPubMedPubMedCentral

Carbonara S, Monno L, Longo, BAngarano, G. Community-acquired pneumonia. Curr Opin Pulm Med. 2009;15(3):261–73. https://doi.org/10.1097/MCP.0b013e3283287c3f.CrossRefPubMed

Tao LL, Hu BJ, He LX, Wei L, Xie HM, Wang BQ, et al. Etiology and antimicrobial resistance of community-acquired pneumonia in adult patients in China. Chin Med J. 2012;125(17):2967–72.PubMed

Schlaberg R, Chiu CY, Miller S, Procop GW, Weinstock G, the Professional Practice Committee and Committee on Laboratory Practices of the American Society for Microbiology, et al. Validation of metagenomic next-generation sequencing tests for universal pathogen detection. Arch Pathol Lab Med. 2017;141(6):776–86. https://doi.org/10.5858/arpa.2016-0539-RA.CrossRefPubMed

Ewig S, Torres A, Angeles Marcos M, Angrill J, Rano A, de Roux A, et al. Factors associated with unknown aetiology in patients with community-acquired pneumonia. Eur Respir J. 2002;20(5):1254–62. https://doi.org/10.1183/09031936.02.01942001.CrossRefPubMed

10.

Louie JK, Hacker JK, Gonzales R, Mark J, Maselli JH, Yagi S, et al. Characterization of viral agents causing acute respiratory infection in a San Francisco University medical center clinic during the influenza season. Clin Infect Dis. 2005;41(6):822–8. https://doi.org/10.1086/432800.CrossRefPubMed

11.

Wilson MR, Naccache SN, Samayoa E, Biagtan M, Bashir H, Yu G, et al. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med. 2014;370(25):2408–17. https://doi.org/10.1056/NEJMoa1401268.CrossRefPubMedPubMedCentral

12.

Chiu CY, Miller SA. Clinical metagenomics. Nat Rev Genet. 2019;20(6):341–55. https://doi.org/10.1038/s41576-019-0113-7.CrossRefPubMedPubMedCentral

13.

Forbes JD, Knox NC, Ronholm J, Pagotto F, Reimer A. Metagenomics: The Next Culture-Independent Game Changer. Front Microbiol. 2017;8:1069. https://doi.org/10.3389/fmicb.2017.01069.CrossRefPubMedPubMedCentral

14.

Blauwkamp TA, Thair S, Rosen MJ, Blair L, Lindner MS, Vilfan ID, et al. Analytical and clinical validation of a microbial cell-free DNA sequencing test for infectious disease. Nat Microbiol. 2019;4(4):663–74. https://doi.org/10.1038/s41564-018-0349-6.CrossRefPubMed

15.

Wilson MR, Sample HA, Zorn KC, Arevalo S, Yu G, Neuhaus J, et al. Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. N Engl J Med. 2019;380(24):2327–40. https://doi.org/10.1056/NEJMoa1803396.CrossRefPubMedPubMedCentral

16.

Miller S, Naccache SN, Samayoa E, Messacar K, Arevalo S, Federman S, et al. Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid. Genome Res. 2019;29(5):831–42. https://doi.org/10.1101/gr.238170.118.CrossRefPubMedPubMedCentral

17.

Gu W, Deng X, Lee M, et al. Rapid pathogen detection by metagenomic next-generation sequencing of infected body fluids. Nat Med. 2020. https://doi.org/10.1038/s41591-020-1105-z.

18.

Zhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727–33.

19.

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507–13. https://doi.org/10.1016/S0140-6736(20)30211-7.CrossRefPubMedPubMedCentral

20.

Ren LL, Wang YM, Wu ZQ, Xiang ZC, Guo L, Xu T, et al. Identification of a novel coronavirus causing severe pneumonia in human: a descriptive study. Chin Med J. 2020;133(9):1015–24. https://doi.org/10.1097/cm9.0000000000000722.CrossRefPubMedPubMedCentral

21.

Langelier C, Kalantar KL, Moazed F, Wilson MR, Crawford ED, Deiss T, et al. Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults. Proc Natl Acad Sci. 2018;115(52):E12353–62. https://doi.org/10.1073/pnas.1809700115.CrossRefPubMedPubMedCentral

22.

Ai JW, Zhang Y, Zhang HC, Xu T, Zhang WH. Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned. Emerg Microbes Infect. 2020;9(1):597–600. https://doi.org/10.1080/22221751.2020.1738905.CrossRefPubMedPubMedCentral

23.

Chen X, Cao K, Wei Y, Qian Y, Liang J, Dong D, et al. Metagenomic next-generation sequencing in the diagnosis of severe pneumonias caused by chlamydia psittaci. Infection. 2020;48(4):535–42. https://doi.org/10.1007/s15010-020-01429-0.CrossRefPubMedPubMedCentral

24.

Di Pasquale MF, Sotgiu G, Gramegna A, et al. Prevalence and etiology of community-acquired pneumonia in Immunocompromised patients. Clin Infect Dis. 2019;68(9):1482–93. https://doi.org/10.1093/cid/ciy723.CrossRefPubMed

25.

Zinter MS, Dvorak CC, Mayday MY, Iwanaga K, Ly NP, McGarry ME, et al. Pulmonary metagenomic sequencing suggests missed infections in Immunocompromised children. Clin Infect Dis. 2019;68(11):1847–55. https://doi.org/10.1093/cid/ciy802.CrossRefPubMed

26.

Wang K, Li P, Lin Y, et al. Metagenomic diagnosis for a culture-negative sample from a patient with severe pneumonia by nanopore and next-generation sequencing. Front Cell Infect Microbiol. 2020;10. https://doi.org/10.3389/fcimb.2020.00182.

27.

Cao B, Huang Y, She DY, Cheng QJ, Fan H, Tian XL, et al. Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese thoracic society, Chinese Medical Association. Clin Respir J. 2018;12(4):1320–60. https://doi.org/10.1111/crj.12674.CrossRefPubMed

28.

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia an official clinical practice guideline of the American thoracic society and infectious diseases society of America. Am J Respir Crit Care Med. 2019;200(7):e45–67. https://doi.org/10.1164/rccm.201908-1581ST.CrossRefPubMedPubMedCentral

29.

Niewiński G, Starczewska, MKański, A. Prognostic scoring systems for mortality in intensive care units--the APACHE model. Anaesthesiol Intensive Ther. 2014;46(1):46–9. https://doi.org/10.5603/ait.2014.0010.CrossRefPubMed

30.

Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics. 2009;25:1754–60. https://doi.org/10.1093/bioinformatics/btp324.CrossRefPubMedPubMedCentral

31.

Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis. 2018;66(5):778–88. https://doi.org/10.1093/cid/cix881.CrossRefPubMed

32.

Greninger AL. The challenge of diagnostic metagenomics. Expert Rev Mol Diagn. 2018;18(7):605–15. https://doi.org/10.1080/14737159.2018.1487292.CrossRefPubMed

33.

Miao Q, Ma Y, Wang Q, Pan J, Zhang Y, Jin W, et al. Microbiological diagnostic performance of metagenomic next-generation sequencing when applied to clinical practice. Clincal Infect Dis. 2018;67(suppl_2):S231–s240. https://doi.org/10.1093/cid/ciy693.CrossRef

34.

Ramachandran PS, Wilson MR. Metagenomics for neurological infections - expanding our imagination. Nat Rev Neurol. 2020;16(10):547–56. https://doi.org/10.1038/s41582-020-0374-y.CrossRefPubMedPubMedCentral

35.

Han D, Li Z, Li R, Tan P, Zhang R, Li J. mNGS in clinical microbiology laboratories: on the road to maturity. Crit Rev Microbiol. 2019;45(5-6):668–85. https://doi.org/10.1080/1040841x.2019.1681933.CrossRefPubMed

36.

Zhang YZ, Shi M, Holmes EC. Using metagenomics to characterize an expanding virosphere. Cell. 2018;172(6):1168–72. https://doi.org/10.1016/j.cell.2018.02.043.CrossRefPubMed

Title: Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia
Authors: Fei Xie
Zhimei Duan
Weiqi Zeng
Shumei Xie
Mingzhou Xie
Han Fu
Qing Ye
Teng Xu
Lixin Xie
Publication date: 01-12-2021
Publisher: BioMed Central
Keyword: Community-Acquired Pneumonia
Published in: BMC Infectious Diseases / Issue 1/2021
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-021-06039-1

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Clinical metagenomics assessments improve diagnosis and outcomes in community-acquired pneumonia

Abstract

Background

Results

Conclusions

Trial registration

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2021

Sex-based clinical and immunological differences in COVID-19

Effectiveness of sepsis bundle application and outcomes predictors to cirrhotic patients with septic shock

Early prediction of blood stream infection in a prospectively collected cohort

COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis

Immature granulocyte percentage for prediction of sepsis in severe burn patients: a machine leaning-based approach

Effect and implementation experience of intensive adherence counseling in a public HIV care center in Uganda: a mixed-methods study

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page