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. Jo 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. The VAPrapid 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

Microbial cultures for the diagnosis of pneumonia take several days to return a result, and are frequently negative, compromising 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% CI 88-100%). Prospectively 95 patients were tested by TAC, with 71 forming the comparator group. TAC returned results 51 hours (IQR 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 (OR 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.

Trial registration

The prospective study was registered with <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="http://clinicaltrials.gov">clinicaltrials.gov</ext-link><ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT03996330">NCT03996330</ext-link>

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