Combination biomarkers to diagnose sepsis in the critically ill patient

Am J Respir Crit Care Med. 2012 Jul 1;186(1):65-71. doi: 10.1164/rccm.201201-0037OC. Epub 2012 Apr 26.


Rationale: 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.

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.

Measurement and main 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Calcitonin / blood*
  • Calcitonin Gene-Related Peptide
  • Critical Illness
  • Humans
  • Logistic Models
  • Membrane Glycoproteins / blood*
  • Myeloid Cells / metabolism
  • Predictive Value of Tests
  • Prospective Studies
  • Protein Precursors / blood*
  • ROC Curve
  • Receptors, IgG / analysis
  • Receptors, Immunologic / blood*
  • Sepsis / diagnosis*
  • Triggering Receptor Expressed on Myeloid Cells-1


  • Biomarkers
  • CALCA protein, human
  • Membrane Glycoproteins
  • Protein Precursors
  • Receptors, IgG
  • Receptors, Immunologic
  • TREM1 protein, human
  • Triggering Receptor Expressed on Myeloid Cells-1
  • Calcitonin
  • Calcitonin Gene-Related Peptide