DIAGNOSING PEDIATRIC SEPSIS WITH SEPTICYTE RAPID HOST GENE EXPRESSION

Abstract

INTRODUCTION: Approximately 3.4 million children die from sepsis worldwide annually. Early identification and treatment of infection have been shown to improve outcomes. SeptiCyte® RAPID is a two gene (PLA2G7 and PLAC8) m-RNA expression biomarker with FDA-510(k) clearance for distinguishing sepsis from non-infectious systemic inflammation in adults. We hypothesized that the same biomarker would accurately diagnose sepsis in children. METHODS: This abstract reports the collective findings of four descriptive cohort investigations conducted at two pediatric hospitals in the US and Australia. Subjects were critically ill children 1 mo-18 yr, admitted to a PICU, undergoing a septic work-up and/or exhibiting modified systemic inflammatory response syndrome (SIRS) criteria. Real-time or deferred, parental permission, was obtained for all subjects. Clinical data and a PAXgene blood sample were collected within 24 hr of PICU admission. RT-qPCR Cq gene expression data generated a SeptiScore® (range 0-15) with four interpretation bands, higher scores indicating higher sepsis probability. SeptiCyte® RAPID clinical performance was evaluated by using AUROC comparison to retrospective physician diagnosis with sepsis operationally defined as SIRS with documented or highly suspected infection. RESULTS: The collective dataset included 284 patients (US cohort n=125; Australia cohort n=159). Probability of sepsis correlated with increasing SeptiScore®. AUROC comparing children with sepsis versus non-infectious SIRS was 0.83 (p=4.3 e-19, 95% CI: 0.78-0.89 [DeLong's test]) using consensus adjudication (n=224, US cohort n=117, Australia cohort n=107). Sepsis likelihood ratios based on SeptiScore® interpretation band for consensus adjudication were: Band 1 (low risk), 0.14 (95% CI: 0.06-0.25); Band 2, 0.48 (95% CI: 0.27-0.87); Band 3, 2.24 (95% CI: 1.16-7.62); and Band 4 (high risk), 3.54 (95% CI: 2.36- 6.18). CONCLUSIONS: In this collective cohort SeptiCyte® RAPID differentiated critically ill children with sepsis compared to those with infection negative SIRS with good predictive power. As this biomarker is now available in real time (∼60 min) it may be useful for detection of sepsis in its early stages, even before organ dysfunction, when treatment could be most effective.