Introduction: Over-diagnosis of VAP results in overuse of antibiotics driving emergence of antimicrobial resistance. Detection of volatile organic compounds (VOCs) in exhaled breath of critically ill patients may offer a useful ?rule-out? test to enhance antimicrobial stewardship.

Methods: BRAVo was a prospective observational cohort study in five UK Intensive Care Units. Mechanically ventilated patients commenced on antibiotics for suspected VAP were recruited within the first 24h of treatment. Paired exhaled breath and respiratory tract samples were collected, and a second breath sample at 48-72h. Breath was analysed using gas chromatography-mass spectrometry. Microbiological culture of a significant growth of pathogenic bacteria in respiratory tract samples confirmed VAP. Univariate and multivariate analysis of VOCs were performed to identify potential biomarkers for a ?rule-out? test.

Results: Samples were analysed from 92 participants (70 provided a second sample). The clinical pneumonia infection score had a negative predicative value of 0.67. Five of seven compounds previously identified in VAP studies were confirmed to be associated with VAP (p<0.05) and four of these changed with treatment. Of all VOCs measured, the four highest performing candidate biomarkers at 95% sensitivity were benzene, cyclohexanone, C₅H₁₁OH and undecanal, each with a negative predictive value of 0.88.

Conclusion: VOCs in the exhaled breath of critically ill patients show promise as a useful non-invasive ?rule-out? test for VAP allowing avoidance of unnecessary antibiotic treatments. A prospective study is now warranted to validate these potential biomarkers.