Background
Abdominal sepsis is a severe condition that requires early and goal-directed treatment. Analysis of volatile organic compounds (VOCs) in exhaled air has shown the potential to rapidly identify causative microorganisms. The common bacteria in abdominal sepsis, Escherichiae coli (E.coli) and Enterococcus faecalis (E.faecalis) could be discriminated in vitro based on their specific VOCs. This study investigates the potential of VOC analysis in exhaled breath to differentiate between E.coli and E.faecalis in a murine model of mono-microbial abdominal sepsis.

Methods
Male C57Bl/6 mice received an intraperitoneal injection with 200uL of 10^8 CFU/ml E.coli (n=20) or 200uL of 10^9CFU/ml E.faecalis (n=20) to induce sepsis. Exhaled breath was collected on stainless steel desorption tubes (1TD/Carbopack X) using a custom-made breath sampling device prior to the injection and 1, 3, 6 and 12 hours thereafter. Plasma levels of IL-6 were determined (t = 6 and 12 hours) using Luminex. Breath samples were analyzed by thermal desorption-gas chromatography combined with time-of-flight mass spectrometry. Random Forest was used to find specific VOCs to discriminate between the two groups and results were visualized by means of Principal Coordinate Analysis (PCoA).

Results
Based on 30 distinctive VOCs for E.coli and 42 distinctive VOCs for E.faecalis development of sepsis could be detected at 1 hour after the injection, before mice were clinically ill. IL-6 levels were elevated at t=6 (2980 [-849-6809] pg/ml for E.coli and 10905 [6145-15667] pg/ml for E.faecalis) and decreased again at t=12. Moreover, a set of 50 VOCs enables clear distinction between sepsis induced by E.coli and E.faecalis.

Conclusion
This study shows the potential of VOC analysis in exhaled air to rapidly detect abdominal sepsis and discriminate causative pathogens. Future research will be directed to evaluate the use of exhaled air analysis in the clinical setting to timely detect abdominal sepsis and guide treatment accordingly.