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.

Publication Date

2025-02-17

Publication Title

Intensive Care Medicine

Volume

51

Issue

2

ISSN

0342-4642

Acceptance Date

2024-12-22

Deposit Date

2025-02-25

Funding

This research was funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number: RP-PG-0514-20018). Infrastructure support was provided by the NIHR University College London and Imperial College London Biomedical Research Centres. The views expressed are those of the authors and not necessarily those of the NIHR, or the Department of Health and Social Care. The study funder had no role in design, data collection, data analysis, data interpretation, or writing of the manuscript. biom\u00E9rieux provided FilmArray Torch instruments, Pneumonia Panel tests and quality control materials free of charge. The manufacturer had no input into the conception, design, data analysis or interpretation of the study and no input into writing of the manuscript. DB reports payments for educational sessions from bioM\u00E9rieux and Gilead and consultancy fees from Paion. VE reports consultancy and speaker fees from bioM\u00E9rieux, personal fees from Alchemab Therapeutics, and in-kind contributions from Inflammatix Inc. JOG has reports personal fees and/or in-kind contributions and/or research funding from Oxford Nanopore Technologies (ONT), Simcere, Becton\u2013Dickinson and Heraeus Medical. He is now an employee of ONT and holds shares in the company. VG reports speaker fees from bioM\u00E9rieux and consultancy fees from Gilead, MSD, Pfizer and Shionogi. JH reports consultancy fees from bioM\u00E9rieux. HK reports speaker fees from bioM\u00E9rieux. DML reports personal fees from Adjutec, AstraZeneca, bioM\u00E9rieux, Centauri, GenPax, GSK, Hikma, Merck/MSD, Nordic, Paion, Pfizer, Shionogi, Sumitovant, Summit, Thermofisher, Wockhardt and Zambon, He also reports shareholdings from GenPax, GSK, Merck, Oxford Nanopore and PerkinElmer/Revvity, comprising less than 10% of portfolio value. He also has nominated holdings in Arecor, Celadon Pharmaceuticals, Destiny Pharma, Eluceda Ltd., Genedrive, Poolbeg, Optibiotix, Probiotix Health, SkinBiotherapeutics, Trellus and Verici Dx (all of which have research/products pertinent to medical and diagnostic innovation) through Enterprise Investment Schemes but has no authority to trade these shares directly. All are outside the submitted work. All other authors declare no competing interests.

Keywords

Adult, Aged, Anti-Bacterial Agents/therapeutic use, Antimicrobial Stewardship/methods, Child, Female, Healthcare-Associated Pneumonia/drug therapy, Humans, Intensive Care Units/statistics & numerical data, Length of Stay/statistics & numerical data, Male, Middle Aged, Pneumonia, Ventilator-Associated/drug therapy, Polymerase Chain Reaction/methods, Standard of Care, Treatment Outcome, Molecular diagnostics, Rapid PCR, Ventilator-associated pneumonia (VAP), Hospital-acquired pneumonia (HAP), Syndromic PCR, Antibiotic stewardship, Point-of-care

First Page

272

Last Page

286

Download

Share

COinS