Diagnosing sepsis in the ICU: Comparison of a gene expression signature to pre-existing biomarkers

Purpose: We aimed to identify a gene signature that discriminates between sepsis and aseptic inflammation in patients administered antibiotics in the intensive care unit and compare it to commonly utilised sepsis biomarkers.Methods: 91 patients commenced on antibiotics were retrospectively diagnosed as having: (i) blood culture positive sepsis; (ii) blood culture negative sepsis; or (iii) aseptic inflammation. Bloods were collected after <24 h of antibiotic commencement for both gene expression sequencing analysis and measurement of previously identified biomarkers.Results: 53 differentially expressed genes were identified that accurately discriminated between blood culture positive sepsis and aseptic inflammation in a cohort of patients given antibiotics [aROC 0.97 (95% CI, 0.95-0.99)]. This gene signature was validated in a publicly available database. The gene signature out-performed previously identified sepsis biomarkers including C-reactive protein [aROC 0.72 (95% CI, 0.57-0.87)], NT-Pro B-type Natriuretic Peptide [aROC 0.84 (95% CI, 0.73-0.96)], and SepticyteTM LAB [aROC 0.8 (95% CI, 0.68-0.93)], but was comparable to Procalcitonin [aROC 0.96 (95% CI, 0.9-1)].Conclusions: A gene expression signature was identified that accurately discriminates between sepsis and aseptic inflammation in patients given antibiotics in the intensive care unit.

Automated summary

This study aimed to identify a gene signature that can discriminate between sepsis and aseptic inflammation in ICU patients receiving antibiotics, and compare it to commonly used sepsis biomarkers. Through retrospective diagnosis of 91 patients on antibiotics, 53 differentially expressed genes were identified that accurately distinguished between blood culture positive sepsis and aseptic inflammation. This gene signature was validated in a publicly available database and outperformed previously identified sepsis biomarkers.