Identification of Potential Urinary Metabolite Biomarkers of Pseudomonas aeruginosa Ventilator-Associated Pneumonia. Issue 17 (May 2022)

• Record Type: Journal Article
• Authors: Jongers, Bart's; Hotterbeekx, An; Bielen, Kenny; Vervliet, Philippe; Boddaert, Jan; Lammens, Christine; Fransen, Erik; Baggerman, Geert; Covaci, Adrian; Goossens, Herman; Malhotra-Kumar, Surbhi; Jorens, Philippe G; Kumar-Singh, Samir
• Is Part Of: Biomarker insights. Volume 2022:Issue 17(2022)
• Publication Date: 2022-05
• Subjects: Hospital-acquired pneumonia -- VAP -- Pseudomonas aeruginosa -- urine biomarkers -- metabolomics -- mass spectrometry; Biochemical markers -- Periodicals; 572.43
• DOI: 10.1177/11772719221099131
• Languages: English
• ISSNs: 1177-2719

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.