Combination Biomarkers to Diagnose Sepsis in the Critically Ill Patient

Rationale: Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessmentofinfectionincriticallyillpatientsisoftenachallengefor clinicians. Inthissetting,simple biomarkers, especiallywhenusedin combination, could prove useful. Objectives: To determine the usefulness of combination biomarkers to diagnose sepsis. Methods: Three hundred consecutive patients were enrolled to construct a biologic score that was next validated in an independent prospective cohort of 79 critically ill patients from another center. MeasurementandMainResults:Plasmaconcentrationsofsolubletriggering receptor expressed on myeloid cells-1 (sTREM-1) and procalcitonin (PCT) were assayed, and the expression of the high-affinity immunoglobulin-Fc fragment receptor I (FcgRI) CD64 on neutrophils (polymorphonuclear [PMN] CD64 index) in flow cytometry was measured. A “bioscore” combining these biomarkers was constructed. Serum concentrations of PCT and sTREM-1 and the PMN CD64 index were higher in patients with sepsis compared with all others (P , 0.001 for the three markers). These biomarkers were all independent predictors of infection, the best receiver-operating characteristic curve being obtained for the PMN CD64 index. The performance of the bioscore, better than that of each individual biomarker, was externally confirmed in the validation cohort. Conclusions: This prospective study, including inceptive and valida