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Research letter
16S pan-bacterial PCR can accurately identify patients with ventilator-associated pneumonia
  1. Andrew Conway Morris1,2,
  2. Naomi Gadsby3,
  3. James P McKenna4,
  4. Thomas P Hellyer5,
  5. Paul Dark6,7,
  6. Suveer Singh8,
  7. Timothy S Walsh2,
  8. Danny F McAuley9,10,
  9. Kate Templeton3,
  10. A John Simpson5,
  11. Ronan McMullan4,9
  1. 1 Division of Anaesthesia, Department of Medicine, University of Cambridge, Cambridge, UK
  2. 2 Centre for Inflammation Research, University of Edinburgh, Edinburgh, UK
  3. 3 Department of Clinical Microbiology, NHS Lothian, Edinburgh, UK
  4. 4 Department of Microbiology, Belfast Health & Social Care Trust, Belfast, UK
  5. 5 Institute of Cellular Medicine, Newcastle University, Newcastle, UK
  6. 6 Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre, Manchester, UK
  7. 7 Intensive Care Unit, Salford Royal NHS Foundation Trust, Greater Manchester, UK
  8. 8 Intensive Care Unit, Chelsea and Westminster Hospital, Imperial College London, London, UK
  9. 9 Centre for Infection and Immunity, Queen's University Belfast, UK
  10. 10 Intensive Care Unit, Royal Victoria Infirmary, Belfast, UK
  1. Correspondence to Professor A John Simpson, Institute of Cellular Medicine, Medical School, Newcastle University, Framlington Place, 3rd Floor, William Leech Building, Newcastle upon Tyne NE2 4HH, UK; j.simpson{at}newcastle.ac.uk

Abstract

Ventilator-associated pneumonia (VAP) remains a challenge to intensive care units, with secure diagnosis relying on microbiological cultures that take up to 72 hours to provide a result. We sought to derive and validate a novel, real-time 16S rRNA gene PCR for rapid exclusion of VAP. Bronchoalveolar lavage (BAL) was obtained from two independent cohorts of patients with suspected VAP. Patients were recruited in a 2-centre derivation cohort and a 12-centre confirmation cohort. Confirmed VAP was defined as growth of >104 colony forming units/ml on semiquantitative culture and compared with a 16S PCR assay. Samples were tested from 67 patients in the derivation cohort, 10 (15%) of whom had confirmed VAP. Using cycles to cross threshold (Ct) values as the result of the 16S PCR test, the area under the receiver operating characteristic (ROC) curve (AUROC) was 0.94 (95% CI 0.86 to 1.0, p<0.0001). Samples from 92 patients were available from the confirmation cohort, 26 (28%) of whom had confirmed VAP. The AUROC for Ct in this cohort was 0.89 (95% CI 0.83 to 0.95, p<0.0001). This study has derived and assessed the diagnostic accuracy of a novel application for 16S PCR. This suggests that 16S PCR in BAL could be used as a rapid test in suspected VAP and may allow better stewardship of antibiotics.

Trial registration number VAPRAPID trial ref NCT01972425.

  • Pneumonia
  • Assisted Ventilation
  • Bacterial Infection

This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 4.0) license, which permits others to distribute, remix, adapt and build upon this work, for commercial use, provided the original work is properly cited. See: http://creativecommons.org/licenses/by/4.0/

https://doi.org/10.1136/thoraxjnl-2016-209065

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    Footnotes

    • Contributors ACM designed the study, obtained funding, recruited patients, analysed data and wrote the manuscript. NG performed the assays, analysed the data and revised the manuscript. JPMcK performed the assays, analysed the data and revised the manuscript. TPH designed the study, recruited patients and revised the manuscript. PD recruited patients, obtained samples and revised the manuscript. SS recruited patients, obtained samples and revised the manuscript. TSW recruited patients, obtained samples and revised the manuscript. DFM recruited patients, obtained samples and revised the manuscript. KT obtained the funding, designed and supervised the assays, and wrote the manuscript. AJS designed the study, obtained funding, recruited patients and wrote the manuscript. RMcM obtained the funding, designed and supervised the assays, and wrote the manuscript.

    • Funding This study was funded by: the Northern Ireland Health and Social Care Research and Development division; the Hospital Infection Society; the Department of Health and Wellcome Trust through the Health Innovation Challenge Fund (HICF)(0510/078); and the Sir Jules Thorn Charitable Trust (03/JTA).

    • Competing interests ACM is a member of the advisory board of Serendex and is chief investigator on a diagnostics study jointly funded by Innovate UK and Becton Dickinson. KT has worked on evaluations of diagnostic systems for Becton Dickinson, Cepheid, Enigma, GenMark and SelexRM has received research grant income from Innovate UK for a diagnostics consortium (with Randox Diagnostics Ltd), investigator-led grant income from Pfizer Ltd and is a consultant/advisor for Gilead Sciences Ltd. All other authors declare no conflicts of interest.

    • Patient consent Obtained.

    • Ethics approval Lothian Research Ethics Committee (REC), NRES North East REC, Scotland A REC.

    • Provenance and peer review Not commissioned; externally peer reviewed.