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

Abstract

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 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)].

Conclusions: A gene expression signature was identified that accurately discriminates between sepsis and aseptic inflammation in patients given antibiotics in the intensive care unit.

Keywords: Biomarker; Gene expression; Intensive care; Sepsis; Sequencing.