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

Ove Andersen,Michael Tvede,Jesper Eugen-Olsen,Gitte Kronborg,Kristian Kofoed,Klaus Larsen,Janne Petersen

doi:10.1186/cc5723

Abstract

IntroductionAccurate 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.MethodsThis 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.ResultsA 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.ConclusionCombining 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.Trial registrationNCT 00389337

Highlights

Accurate and timely diagnosis of communityacquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory
The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [confidence intervals (CIs)] 0.40 to 0.60) for soluble urokinase-type plasminogen activator receptor (suPAR), 0.61 for soluble triggering receptor expressed on myeloid cells (sTREM)-1, 0.63 for migration inhibitory factor (MIF), 0.72 for PCT, 0.74 for neutrophil count, 0.81 for C-reactive protein (CRP), 0.84 for the composite three-marker test, and 0.88 for the composite six-marker test
AUC = area under the receiver operating characteristic curve; CI = confidence interval; CRP = C-reactive protein; intensive care units (ICUs) = intensive care unit; MIF = macrophage migration inhibitory factor; PCT = procalcitonin; ROC = receiver operating characteristic; SIRS = systemic inflammatory response syndrome; SOFA = Sequential Organ Failure Assessment; suPAR = soluble receptors urokinase-type plasminogen activator; sTREM = soluble triggering receptor expressed on myeloid cells

Summary

Introduction

Accurate and timely diagnosis of communityacquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Clinical and laboratory signs of systemic inflammation, including changes in body temperature, tachycardia, respiratory rate and leucocytosis, are sensitive Their use is limited by poor specificity for the diagnosis of sepsis, because critically ill patients often present with the systemic inflammatory response syndrome (SIRS) but no infection [1,4,5,6]. These issues have fuelled the search for a reliable marker. The search for a single magic bullet marker might be fruitless, but a combination of markers could improve diagnosis, prognosis and treatment efficacy, and thereby survival [7]

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