Circulating metabolome as key biomarkers for ventilator-associated pneumonia: Case–Control study in a tertiary care hospital of North India

ABSTRACT Introduction: Ventilator-associated pneumonia (VAP) is a microbial infection that develops in the lungs when a patient has been intubated for mechanical ventilation for more than 48 h. Diagnosis of VAP remains a challenge despite clinical advances. NMR-based metabolomics might play a pivotal role in overcoming the diagnostic complexity of VAP by investigating biomarkers. Materials and Methods: This case–control study was conducted in 2024–2025 at Sir Sunder Lal Hospital, Varanasi. The participated patients had an intubation period of more than 48 h; a total of 44 patients were recruited, of which 20 patients developed VAP and 24 were non-VAP patients. NMR spectra of serum were recorded, and statistical analysis was done. Results: The 2D scatter plot of PC1 versus PC2 scores clearly shows a distinction between the groups, with the principal component analysis explaining 18.9% of the variance. Partial least-squares discriminant analysis demonstrated R 2 and Q 2 values of 0.328 and 0.0552, respectively, indicating a probability to model fit. A total of 27 distinct metabolites were identified. Univariate receiver operating characteristic curve analysis identified phenylalanine (area under the curve [AUC] = 0.720), acetoacetate (AUC = 0.706), and glutamate (AUC = 0.690) as significant metabolites. With AUC values within the fair accuracy range, these three metabolites are considered acceptable biomarkers for the diagnosis of VAP. Conclusion: The elevated metabolites indicate lung injury and perturbed inflammatory pathways, which may result from invasive mechanical ventilation. We conclude that the levels of phenylalanine, acetoacetate, and glutamate may serve as biomarkers and aid in the diagnosis of VAP, disease monitoring, and therapeutic stratification.