Authors

INHALE WP3 Study Group and Committees
Virve I Enne, University College London
Susan Stirling, University of East Anglia
Julie A Barber, University College London
Juliet High, University of East Anglia
Charlotte Russell, University of East Anglia
David Brealey, University College London Hospitals
Zaneeta Dhesi, University College London
Antony Colles, University of East Anglia
Suveer Singh, Chelsea and Westminster Hospital NHS Foundation Trust
Robert Parker, Aintree University Hospital
Mark Peters, UCL Great Ormond St Institute of Child Health NIHR Biomedical Research Centre
Benny P Cherian, Microbiology and Infectious Diseases, Barts Health NHS Trust, London, UK.
Peter Riley, St George's University Hospitals NHS Foundation Trust
Matthew Dryden, Hampshire Hospitals NHS Foundation Trust
Ruan Simpson, Portsmouth Hospitals University NHS Trust
Nehal Patel, University Hospitals of North Midlands NHS Trust
Jane Cassidy, Birmingham Children's Hospital NHS Foundation Trust
Daniel Martin, Peninsula Medical School
Ingeborg D Welters, Liverpool University Hospitals NHS Foundation Trust
Valerie Page, West Hertfordshire Teaching Hospitals NHS Trust
Hala Kandil, West Hertfordshire Teaching Hospitals NHS Trust
Eleanor Tudtud, BUPA Cromwell Hospital
David Turner, University of East Anglia
Robert Horne, University College London
Justin O'Grady, University of East Anglia
Ann Marie Swart, University of East Anglia
David M Livermore, University of East Anglia
Vanya Gant, University College London Hospitals

ORCID

Abstract

PURPOSE: INHALE investigated the impact of seeking pathogens by PCR on antibiotic stewardship and clinical outcomes in hospital-acquired and ventilator-associated pneumonia (HAP and VAP).

METHODS: This pragmatic multicentre, open-label RCT enrolled adults and children with suspected HAP and VAP at 14 ICUs. Patients were randomly allocated to standard of care, or rapid in-ICU syndromic PCR coupled with optional prescribing guidance. Co-primary outcomes were superiority in antibiotic stewardship at 24 h and non-inferiority in clinical cure of pneumonia 14 days post-randomisation. Secondary outcomes included mortality, ICU length of stay and evolution of clinical scores.

RESULTS: 554 eligible patients were recruited from 5th July 2019 to 18th August 2021, with a COVID-enforced pause from 16th March 2020 and 9th July 2020. Data were analysed for 453 adults and 92 children (68.4% male; 31.6% female). ITT analysis showed 205/268 (76.5%) reviewable intervention patients receiving antibacterially appropriate and proportionate antibiotics at 24 h, versus 147/263 (55.9%) standard-of-care patients (estimated difference 21%; 95% CI 13-28%). However, only 152/268 (56.7%) intervention patients were deemed cured of pneumonia at 14 days, versus 171/265 (64.5%) standard-of-care patients (estimated difference - 6%, 95% CI - 15 to 2%; predefined non-inferiority margin -13%). Secondary mortality and ΔSOFA outcomes narrowly favoured the control arm, without clear statistical significance.

CONCLUSIONS: In-ICU PCR for pathogens resulted in improved antibiotic stewardship. However, non-inferiority was not demonstrated for cure of pneumonia at 14 days. Further research should focus on clinical effectiveness studies to elucidate whether antibiotic stewardship gains achieved by rapid PCR can be safely and advantageously implemented.

DOI

10.1007/s00134-024-07772-2

Publication Date

2025-02-17

Publication Title

Intensive Care Medicine

ISSN

0342-4642

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