Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study.
BACKGROUND
Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination.


METHODS
This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed - one including a linear combination of the three best performing markers and another including all six - and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers.


RESULTS
A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers.


CONCLUSIONS
Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics.
Kofoed
Kristian
K
Clinical Research Unit, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. kristian.kofoed@hvh.regionh.dk
Andersen
Ove
O
Kronborg
Gitte
G
Tvede
Michael
M
Petersen
Janne
J
Eugen-Olsen
Jesper
J
Larsen
Klaus
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001424:Bacterial Infections / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D015331:Cohort Studies; D017714:Community-Acquired Infections / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D007958:Leukocyte Count; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D009504:Neutrophils; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D011956:Receptors, Cell Surface / Q000097:blood*; D011971:Receptors, Immunologic / Q000097:blood*; D055293:Receptors, Urokinase Plasminogen Activator; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D015415:Biomarkers; C000606589:CALCA protein, human; D008263:Macrophage Migration-Inhibitory Factors; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D055293:Receptors, Urokinase Plasminogen Activator; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide