Validation of SeptiCyte RAPID to Discriminate Sepsis from Noninfectious Systemic Inflammation in Critically Ill Children

OBJECTIVES:Biomarkers with adequate precision to rule-in/rule-out sepsis in children represent an unmet need. SeptiCyte RAPID is a point-of-care, U.S. Food and Drug Administration-cleared, host gene expression biomarker test for the determination of sepsis probability (reported in 1 hr as a SeptiScore) using a small-volume peripheral blood sample. We have previously reported on SeptiCyte RAPID performance in adults. Here we report a retrospective, noninterventional clinical validation study of SeptiCyte RAPID, as a sepsis diagnostic adjunct in children. DESIGN, SETTING, AND PATIENTS:Critically ill children (n = 284), 1 month to 18 years old, admitted to PICUs, with or without suspected or documented infection, but all of whom met criteria for systemic inflammatory response syndrome (SIRS) and were enrolled at multiple clinical sites in the United States and Australia in four separate studies. INTERVENTIONS:None; SeptiCyte RAPID results were not used to guide patient treatment. MEASUREMENTS AND MAIN RESULTS:A combination of clinical adjudication and an independent panel of three physicians (Retrospective Physician Diagnosis [RPD]), blinded to SeptiCyte RAPID results, were used to retrospectively categorize patients into sepsis vs. noninfectious SIRS categories. Diagnostic performance of SeptiCyte RAPID for differentiating sepsis and noninfectious SIRS compared with RPD was measured using area under the curve (AUC), likelihood ratio, and a monotonic increase in probability of sepsis and increasing SeptiScores. Binomial logistic regression analysis was used to integrate clinical parameters in a model based on SeptiCyte RAPID. Higher SeptiScores correlated with higher probability of sepsis. SeptiCyte RAPID AUC for identifying sepsis in children ranged from 0.80 to 0.83. A model additionally integrating lactate, platelet number, mean arterial pressure, Paco2, mechanical ventilation, weight, age, and leukocyte count increased SeptiCyte RAPID performance (AUC, 0.86; 95% CI, 0.85-0.87). CONCLUSIONS:SeptiCyte RAPID demonstrated similar performance characteristics in children to that previously reported for adults. Additional real world effectiveness studies are warranted to determine real-time clinical utility, patient benefits, and health economic impact.