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ABSTRACT: Introduction
Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of P. aeruginosa-derived markers in easily accessible patients' samples can enable an early detection of P. aeruginosa VAP (VAP-PA), thereby stewarding antibiotic use and improving clinical outcomes.Methods
Metabolites were analysed using liquid chromatography-mass spectrometry (LC-MS) in prospectively collected urine samples from mechanically ventilated patients admitted to the Antwerp University Hospital ICU. Patients were followed from the start of mechanical ventilation (n = 100 patients) till the time of clinical diagnosis of VAP (n = 13). Patients (n = 8) in whom diagnosis of VAP was further confirmed by culturing respiratory samples and urine samples were studied for semi-quantitative metabolomics.Results
We first show that multivariate analyses highly discriminated VAP-PA from VAP-non-PA as well as from the pre-infection groups (R 2 = .97 and .98, respectively). A further univariate analysis identified 58 metabolites that were significantly elevated or uniquely present in VAP-PA compared to the VAP-non-PA and pre-infection groups (P < .05). These comprised both a known metabolite of histidine as well as a novel nicotine metabolite. Most interestingly, we identified 3 metabolites that were not only highly upregulated for, but were also highly specific to, VAP-PA, as these metabolites were completely absent in all pre-infection timepoints and in VAP-non-PA group.Conclusions
Considerable differences exist between urine metabolites in VAP-PA compared to VAP due to other bacterial aetiologies as well to non-VAP (pre-infection) timepoints. The unique urinary metabolic biomarkers we describe here, if further validated, could serve as highly specific diagnostic biomarkers of VAP-PA.
SUBMITTER: Jongers B
PROVIDER: S-EPMC9112676 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Jongers Bart's B Hotterbeekx An A Bielen Kenny K Vervliet Philippe P Boddaert Jan J Lammens Christine C Fransen Erik E Baggerman Geert G Covaci Adrian A Goossens Herman H Malhotra-Kumar Surbhi S Jorens Philippe G PG Kumar-Singh Samir S
Biomarker insights 20220513
<h4>Introduction</h4>Ventilator-associated pneumonia (VAP) caused by <i>Pseudomonas aeruginosa</i> is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of <i>P. aeruginosa</i>-derived markers in easily accessible patients' samples can enable an early detection of <i>P. aeruginosa</i> VAP (VAP-PA), thereby stewarding antibiotic use and improving clinical outcomes.<h4>Methods</h4>Metabolites were analysed using liquid chromatography-mass spectrom ...[more]