Metabolites in Blood for Prediction of Bacteremic Sepsis in the Emergency Room

Abstract

A metabolomics approach for prediction of bacteremic sepsis in patients in the emergency room (ER) was investigated. In a prospective study, whole blood samples from 65 patients with bacteremic sepsis and 49 ER controls were compared. The blood samples were analyzed using gas chromatography coupled to time-of-flight mass spectrometry. Multivariate and logistic regression modeling using metabolites identified by chromatography or using conventional laboratory parameters and clinical scores of infection were employed. A predictive model of bacteremic sepsis with 107 metabolites was developed and validated. The number of metabolites was reduced stepwise until identifying a set of 6 predictive metabolites. A 6-metabolite predictive logistic regression model showed a sensitivity of 0.91(95% CI 0.69–0.99) and a specificity 0.84 (95% CI 0.58–0.94) with an AUC of 0.93 (95% CI 0.89–1.01). Myristic acid was the single most predictive metabolite, with a sensitivity of 1.00 (95% CI 0.85–1.00) and specificity of 0.95 (95% CI 0.74–0.99), and performed better than various combinations of conventional laboratory and clinical parameters. We found that a metabolomics approach for analysis of acute blood samples was useful for identification of patients with bacteremic sepsis. Metabolomics should be further evaluated as a new tool for infection diagnostics.

Metabolomics as a Driver in Advancing Precision Medicine in Sepsis

“…48 Ultimately, the strength and added value of metabolomics in sepsis for both children and adults may be when it is combined with clinical data and other measurements to improve prediction of outcomes and demonstrate enhanced performance when compared with currently available diagnostic tests including procalcitonin, C-reactive protein, and lactate levels. 43,45,55 In an example of this strategy, profiling children early after presentation in the emergency department using metabolomics and inflammatory protein mediators differentiated children who did and did not require ICU care. This application of metabolomics may aid in triage decisions and risk stratification in sepsis, particularly in clinical environments without pediatric expertise.…”

Regulation of leukocyte function by citric acid cycle intermediates

“…In a study involving patients suffering from chronic kidney disease, urinary excretion of succinate, citrate, cis ‐aconitate, and isocitrate were significantly reduced, and this correlated with the renal expression of genes regulating these metabolites . Citric acid was observed to be slightly lower in plasma of bacteremic sepsis cases as compared to controls in a patient population studied in the emergency room . Succinate and citrate have also been shown to be significantly decreased among urinary metabolites in patients suffering from inflammatory bowel diseases, as compared to healthy individuals .…”

Immunotherapy of Sepsis: Blind Alley or Call for Personalized Assessment?

“…Metabolomics is complete analysis of metabolome in given physiological or pathological state of the cell, tissue and organism and it provides new insight on cellular fiction (Goodacre et al 2004). It can be used in septic patients for diagnosis, disease prognosis and for the patient's risk stratification (Ferrario et al 2016;Kauppi et al 2016).…”