Pre-clinical Diagnosis Using Integrated Microbial and Host Response Signatures to Improve Outcomes From Ventilator-associated Pneumonia in Critically Ill Children

Ventilator-associated pneumonia (VAP), defined as pneumonia occurring 48 hours after initiation of invasive mechanical ventilation, is insidious in onset and severe in consequence. It is a critical issue affecting 10-20% of the 26,000 children admitted to the paediatric intensive care unit (PICU) each year. Infection typically leads to extended PICU stay, prolonged invasive mechanical ventilation, and increased mortality. Despite its clinical significance, VAP remains poorly defined, as current diagnosis relies on non-specific criteria and the ability to obtain clinically meaningful cultures. VAP, deviates from conventional pneumonia, potentially originating, from tissue damage, changes to immune processes, and migration of gastrointestinal bacteria into the lung; all associated with prolonged mechanical ventilation. These factors, in combination with the clinical instability of PICU patients, mean that clinicians aggressively start antibiotic therapy despite a paucity of evidence to suggest the best regime. As a result, suspected VAP has been shown to account for nearly 40% of antibiotic exposure in the PICU, which has significant implications on anti-microbial resistance (AMR). To address these challenges, novel diagnostic therapies are needed to optimise the treatment of VAP. These therapies should utilise our current understanding of the pathophysiology of VAP development, specifically, the infiltration of the lung microbiome by gut and oral bacteria during prolonged me…

This description comes directly from the study's public registry record.

Nazima Pathan, FRCPCH PhD  ·  +441223 805000  ·  np409@medschl.cam.ac.uk

Don Laing, MBChB, BMedSci (Hons)  ·  +441223 805000  ·  dml57@cam.ac.uk

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