title: Combination biomarkers to diagnose sepsis in the critically ill patient.
abstract: BACKGROUND
  Although the outcome of sepsis benefits from the prompt administration of appropriate antibiotics on correct diagnosis, the assessment of infection in critically ill patients is often a challenge for clinicians. In this setting, simple biomarkers, especially when used in combination, could prove useful.
  
  
  OBJECTIVE
  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.
  
  
  RESULTS
  Plasma concentrations of soluble triggering 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 (FcγRI) 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 validation cohorts of unselected intensive care unit patients, demonstrates the high performance of a bioscore combining the PMN CD64 index together with PCT and sTREM-1 serum levels in diagnosing sepsis in the critically ill patient.
authors.affiliation: Hôpital Central, Service de Réanimation Médicale, 29 avenue du Maréchal de Lattre de Tassigny, Nancy Cedex, France. s.gibot@chu-nancy.fr
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gibot
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
authors.forename: Robin
authors.initials: R
authors.lastname: Noel
authors.forename: Frédéric
authors.initials: F
authors.lastname: Massin
authors.forename: Julien
authors.initials: J
authors.lastname: Guy
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cravoisy
authors.forename: Damien
authors.initials: D
authors.lastname: Barraud
authors.forename: Marcelo
authors.initials: M
authors.lastname: De Carvalho Bittencourt
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Quenot
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Bollaert
authors.forename: Gilbert
authors.initials: G
authors.lastname: Faure
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Charles
mesh_terms: D015415:Biomarkers / Q000097:blood*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D016638:Critical Illness; D006801:Humans; D016015:Logistic Models; D008562:Membrane Glycoproteins / Q000097:blood*; D022423:Myeloid Cells / Q000378:metabolism; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D012372:ROC Curve; D017452:Receptors, IgG / Q000032:analysis; D011971:Receptors, Immunologic / Q000097:blood*; D018805:Sepsis / Q000175:diagnosis*; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D015415:Biomarkers; C000606589:CALCA protein, human; D008562:Membrane Glycoproteins; D011498:Protein Precursors; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide