Novel fast pathogen diagnosis method for severe pneumonia patients in the intensive care unit: randomized clinical trial

Abstract

Background:

Severe pneumonia is one of the common acute diseases caused by pathogenic bacteria infection, especially by pathogenic bacteria, leading to sepsis with a high morbidity and mortality rate. However, the existing bacteria cultivation method cannot satisfy current clinical needs requiring rapid identification of bacteria strain for antibiotic selection. Therefore, developing a sensitive liquid biopsy system demonstrates the enormous value of detecting pathogenic bacterium species in pneumonia patients.

Methods:

In this study, we developed a tool named Species-Specific Bacterial Detector (SSBD, pronounce as "speed") for detecting selected bacterium. Newly designed diagnostic tools combining specific DNA-tag screened by our algorithm and CRISPR/Cas12a, which were first tested in the lab to confirm the accuracy, followed by validating its specificity and sensitivity via applying on bronchoalveolar lavage fluid (BALF) from pneumonia patients. In the validation I stage, we compared the SSBD results with traditional cultivation results. In the validation II stage, a randomized and controlled clinical trial was completed at the ICU of Nanjing Drum Tower Hospital to evaluate the benefit SSBD brought to the treatment.

Results:

In the validation stage I, 77 BALF samples were tested, and SSBD could identify designated organisms in 4 hours with almost 100% sensitivity and over 87% specific rate. In validation stage II, the SSBD results were obtained in 4 hours, leading to better APACHE II scores (p=0.0035, ANOVA test). Based on the results acquired by SSBD, cultivation results could deviate from the real pathogenic situation with polymicrobial infections. In addition, nosocomial infections were found widely in ICU, which should deserve more attention.

Funding:

National Natural Science Foundation of China. The National Key Scientific Instrument and Equipment Development Project. Project number: 81927808.

Clinical trial:

This study was registered at ClinicalTrilas.gov (NCT04178382).

Data availability

All data generated or analysed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 3-5, Appendix figures 2-5, and Appendix tables 3-9.

Article and author information

Author details

  1. Yan Wang

    Department of Critical Care Medicine, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Xiaohui Liang

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Yuqian Jiang

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Danjiang Dong

    Department of Critical Care Medicine, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Cong Zhang

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Tianqiang Song

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Ming Chen

    Department of Critical Care Medicine, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Yong You

    Department of Critical Care Medicine, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Han Liu

    Department of Critical Care Medicine, Nanjing Medical University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Min Ge

    Department of Cardiothoracic Surgery Intensive Care Unit, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Haibin Dai

    Department of Neurosurgery Intensive Care Unit, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Fengchan Xi

    Research Institute of General Surgery, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Wanqing Zhou

    Department of Laboratory Medicine, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  14. Jian-Qun Chen

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Qiang Wang

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    For correspondence
    wangq@nju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2907-9851
  16. Qihan Chen

    The State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
    For correspondence
    chenqihan@nju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0062-8434
  17. Wenkui Yu

    Department of Critical Care Medicine, Nanjing University, Nanjing, China
    For correspondence
    yudrnj@nju.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4218-0321

Funding

National Natural Science Foundation of China (The National Key Scientific Instrument and Equipment Development Project,81927808)

  • Wenkui Yu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: We acquired the ethics approval (2019-197-01) from the ethics committee of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School in July 2019, registered and posted the complete research protocol, informed consent, subject materials, case report form, researcher manual, the introduction of main researchers and other information in Chinese. Later on, this study was registered in English at ClinicalTrilas.gov (NCT04178382) in November 2019.

Reviewing Editor

  1. Bavesh D Kana, University of the Witwatersrand, South Africa

Publication history

  1. Preprint posted: March 25, 2022 (view preprint)
  2. Received: March 28, 2022
  3. Accepted: October 5, 2022
  4. Accepted Manuscript published: October 7, 2022 (version 1)
  5. Version of Record published: October 26, 2022 (version 2)

Copyright

© 2022, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Yan Wang
  2. Xiaohui Liang
  3. Yuqian Jiang
  4. Danjiang Dong
  5. Cong Zhang
  6. Tianqiang Song
  7. Ming Chen
  8. Yong You
  9. Han Liu
  10. Min Ge
  11. Haibin Dai
  12. Fengchan Xi
  13. Wanqing Zhou
  14. Jian-Qun Chen
  15. Qiang Wang
  16. Qihan Chen
  17. Wenkui Yu
(2022)
Novel fast pathogen diagnosis method for severe pneumonia patients in the intensive care unit: randomized clinical trial
eLife 11:e79014.
https://doi.org/10.7554/eLife.79014
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