Development and implementation of a customised rapid syndromic diagnostic test for severe pneumonia

  1. Vilas Navapurkar
  2. Josefin Bartholdson Scott
  3. Mailis Maes
  4. Thomas P Hellyer
  5. Ellen Higginson
  6. Sally Forrest
  7. Joana Pereira-Dias
  8. Surendra Parmar
  9. Emma Heasman-Hunt
  10. Petra Polgarova
  11. Joanne Brown
  12. Lissamma Titti
  13. William PW Smith
  14. Jonathan Scott
  15. Anthony Rostron
  16. Matthew Routledge
  17. David Sapsford
  18. M. Estée Török
  19. Ronan McMullan
  20. David A Enoch
  21. Vanessa Wong
  22. VAP-Rapid investigators
  23. Martin D Curran
  24. Nicholas M Brown
  25. A John Simpson
  26. Jurgen Herre
  27. Gordon Dougan
  28. Andrew Conway Morris

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Abstract

Background: The diagnosis of pneumonia has been hampered by a reliance on bacterial cultures which take several days to return a result, and are frequently negative. In critically ill patients this leads to the use of empiric, broad-spectrum antimicrobials and compromises good antimicrobial stewardship. The objective of this study was to establish the performance of a syndromic molecular diagnostic approach, using a custom TaqMan array card (TAC) covering 52 respiratory pathogens, and assess its impact on antimicrobial prescribing.

Methods: The TAC was validated against a retrospective multi-centre cohort of broncho-alveolar lavage samples. The TAC was assessed prospectively in patients undergoing investigation for suspected pneumonia, with a comparator cohort formed of patients investigated when the TAC laboratory team were unavailable.

Co-primary outcomes were sensitivity compared to conventional microbiology and, for the prospective study, time to result. Metagenomic sequencing was performed to validate findings in prospective samples. Antibiotic free days (AFD) were compared between the study cohort and comparator group.

Results: 128 stored samples were tested, with sensitivity of 97% (95% confidence interval (CI) 88-100%). Prospectively, 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (interquartile range 41-69 hours) faster than culture and with sensitivity of 92% (95% CI 83-98%) compared to conventional microbiology. 94% of organisms identified by sequencing were detected by TAC. There was a significant difference in the distribution of AFDs with more AFDs in the TAC group (p=0.02). TAC group were more likely to experience antimicrobial de-escalation (odds ratio 2.9 (95%1.5-5.5)).

Conclusions: Implementation of a syndromic molecular diagnostic approach to pneumonia led to faster results, with high sensitivity and impact on antibiotic prescribing.

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  1. Version published to 10.12688/wellcomeopenres.17099.3
  2. Version published to 10.1101/2020.06.02.20118489v4 on medRxiv
  3. Version published to 10.1101/2020.06.02.20118489v3 on medRxiv
  4. Version published to 10.1101/2020.06.02.20118489v2 on medRxiv
  5. ScreenIT

    SciScore for 10.1101/2020.06.02.20118489: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical and regulatory approvals and funding: The study was approved by the Leeds East Research Ethics Committee (17/YH/0286) and registered with clinicaltrials.gov (NCT03996330).
    Consent: The retrospective assessment of routinely collected data from the comparator group received a consent waiver and was conducted under a protocol approved by the institutional review board (A095506).
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisStudy size: As the incidence of infections with specific organisms could only be inferred from conventional culture which is known to be insensitive, a formal power calculation was not performed.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Analysis was conducted using Graphpad prism v5.0 (Graphpad inc, San Diego, CA).
    Graphpad prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT03996330CompletedRapid Pathogen Identification in Ventilated Patients With Pn…

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  6. Version published to 10.1101/2020.06.02.20118489v1 on medRxiv