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 mechanical ventilation. To achieve this, molecular testing should be promoted allowing for rapid identification of lung pathogens. There is also growing evidence, for the investigation of predictive biomarkers for VAP available in both the blood and lungs, which when integrated into protocols may enhance diagnostic accuracy. These novel techniques may improve clinical outcomes for affected children while addressing the economic impact of prolonged hospital stays and mitigating AMR risks in PICUs.
PICU Admission
Requires 48 Hours Of Mechanical Ventilation
Imminent death or palliative care pathway planned
Existing tracheostomy at time of admission
Known immunocompromised patient
Patient received a full course of systemic antimicrobials in the previous 6 weeks.
Critically Ill Children Requiring Mechanical Ventilation For Greater Than 48 Hours
Cohort
Prospective
Not listed
Characterise temporal shifts in microbial composition and the corresponding host immune response during prolonged mechanical ventilation
Serial metagenomic profiling of the lung microbiome to establish microbial shifts. Concurrently, cytokines collected from blood and endotracheal aspirates will be taken to assess immune changes.
Characterise the AMR burden in VAP and its role in shaping the microbiome during infection.
Utilise metagenomic sequencing to identify AMR genes present on microbes and relate this to VAP development
Develop statistical and/or machine learning models leveraging these signatures independently, or in combination, to identify putative microbial and host biomarkers for early VAP diagnosis
Prevalence of VAP
Number of critically ill children requiring mechanical ventilation who develop VAP compared to those who do not
30 day mortality
Mortality status of patients at 30 days
Time To Extubation
Total Time Intubated
Utilisation Of VAP Prevention Bundle
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University of Cambridge
Lead sponsor
Cambridge University Hospitals NHS Foundation Trust
Collaborator
