Abstract

Background: Ventilator-associated pneumonia (VAP) commonly occurs in intensive care patients. Current diagnostic methods risk delayed and inaccurate antimicrobial treatment. Early and accurate detection is therefore vital to improve patient health and reduce spread of antimicrobial resistance. BRAVo was a multi-centre biomarker discovery study with the aim to uncover novel metabolites in the breath and blood with improved diagnostic capability for VAP.

Methods: Blood samples were collected on clinical suspicion of VAP from mechanically ventilated patients. Blood plasma was extracted and immediately frozen until analysis at the end of the study. VAP classification was based on positive microbiological culture of pathogens. Metabolites were extracted from plasma samples and analysed by high resolution liquid chromatography-mass spectrometry. After data pre-processing and treatment, a Mann Whitney-U test with FDR adjustment (0.05) was applied to screen for statistically significant metabolite features between patients with VAP compared to those without VAP.

Results: 91 patient samples [63 male, mean (SD) age 56 (16) yrs] with baseline blood plasma data were included in the analysis. Pathogens were identified in 45 patients and were therefore classified as VAP. Peak intensities of 51 features were elevated (FDR<0.05, fold change>2) in the VAP group whereas only one feature was greater in abundance in patients without VAP.

Conclusion: We have shown differential metabolite profiles between patients with and without VAP, indicative of systemic metabolic change in the host response to infection.