Validation of a Host Response Assay, SeptiCyte LAB, for Discriminating Sepsis from Systemic Inflammatory Response Syndrome in the ICU.
Miller RR., Lopansri BK., Burke JP., Levy M., Opal S., Rothman RE., D'Alessio FR., Sidhaye VK., Aggarwal NR., Balk R., Greenberg JA., Yoder M., Patel G., Gilbert E., Afshar M., Parada JP., Martin GS., Esper AM., Kempker JA., Narasimhan M., Tsegaye A., Hahn S., Mayo P., van der Poll T., Schultz MJ., Scicluna BP., Klein Klouwenberg P., Rapisarda A., Seldon TA., McHugh LC., Yager TD., Cermelli S., Sampson D., Rothwell V., Newman R., Bhide S., Fox BA., Kirk JT., Navalkar K., Davis RF., Brandon RA., Brandon RB.
RationaleA molecular test to distinguish between sepsis and systemic inflammation of noninfectious etiology could potentially have clinical utility.ObjectivesThis study evaluated the diagnostic performance of a molecular host response assay (SeptiCyte LAB) designed to distinguish between sepsis and noninfectious systemic inflammation in critically ill adults.MethodsThe study employed a prospective, observational, noninterventional design and recruited a heterogeneous cohort of adult critical care patients from seven sites in the United States (n = 249). An additional group of 198 patients, recruited in the large MARS (Molecular Diagnosis and Risk Stratification of Sepsis) consortium trial in the Netherlands ( www.clinicaltrials.gov identifier NCT01905033), was also tested and analyzed, making a grand total of 447 patients in our study. The performance of SeptiCyte LAB was compared with retrospective physician diagnosis by a panel of three experts.Measurements and main resultsIn receiver operating characteristic curve analysis, SeptiCyte LAB had an estimated area under the curve of 0.82-0.89 for discriminating sepsis from noninfectious systemic inflammation. The relative likelihood of sepsis versus noninfectious systemic inflammation was found to increase with increasing test score (range, 0-10). In a forward logistic regression analysis, the diagnostic performance of the assay was improved only marginally when used in combination with other clinical and laboratory variables, including procalcitonin. The performance of the assay was not significantly affected by demographic variables, including age, sex, or race/ethnicity.ConclusionsSeptiCyte LAB appears to be a promising diagnostic tool to complement physician assessment of infection likelihood in critically ill adult patients with systemic inflammation. Clinical trial registered with www.clinicaltrials.gov (NCT01905033 and NCT02127502).