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

Abstract

PurposeWe 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. Methods91 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. Results53 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 outperformed 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 Septicyte™ LAB [aROC 0.8 (95% CI, 0.68–0.93)], but was comparable to Procalcitonin [aROC 0.96 (95% CI, 0.9–1)]. ConclusionsA gene expression signature was identified that accurately discriminates between sepsis and aseptic inflammation in patients given antibiotics in the intensive care unit.