Prognostic and diagnostic value of eosinopenia, C-reactive protein, procalcitonin, and circulating cell-free DNA in critically ill patients admitted with suspicion of sepsis

Abstract

Introduction: The aims of this study were to assess the reliability of circulating cell-free DNA (cf-DNA) concentrations, compared with C-reactive protein (CRP), procalcitonin (PCT) and eosinophil count, in the diagnosis of infections in patients with systemic inflammatory response syndrome (SIRS) and their prognostic values in a cohort of critically ill patients.

Methods: We conducted a prospective cohort study in a medical-surgical intensive care unit of a university hospital. Eosinophil count and concentrations of cf-DNA, CRP, and PCT were measured in patients who fulfilled SIRS criteria at admission to the intensive care unit (ICU) and a second determination 24 hours later. DNA levels were determined by a PCR method using primers for the human beta-haemoglobin gene.

Results: One hundred and sixty consecutive patients were included: 43 SIRS without sepsis and 117 with sepsis. Levels of CRP and PCT, but not cf-DNA or eosinophil count, were significantly higher in patients with sepsis than in SIRS-no sepsis group on days 1 and 2. PCT on day 1 achieves the best area under the curve (AUC) for sepsis diagnosis (0.87; 95% confidence interval = 0.81-0.94). Levels of cf-DNA do not predict outcome and the accuracy of these biomarkers for mortality prediction was lower than that shown by APACHE II score. PCT decreases significantly from day 1 to day 2 in survivors in the entire cohort and in patients with sepsis without significant changes in the other biomarkers.

Conclusions: Our data do not support the clinical utility of cf-DNA measurement in critical care patients with SIRS. PCT is of value especially for infection identification in patients with SIRS at admission to the ICU.

Figure 1

Receiver-operating characteristic curves in the total cohort for various biomarker cutoff levels. Receiver-operating characteristic curves in the total cohort for cutoff levels of leukocytes, C-reactive protein (CRP), procalcitonin (PCT), cell-free DNA (cf-DNA) and eosinophils and Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation (APACHE) II scores in differentiating between the presence and absence of sepsis at admission. Areas under the receiver-operating characteristic curves: leukocytes, 0.55 (95% confidence interval (CI), 0.45 to 0.64); CRP, 0.69 (95% CI, 0.59 to 0.79); PCT, 0.87 (95% CI, 0.81 to 0.94); cf-DNA, 0.51 (95% CI, 0.61 to 0.71); eosinophils, 0.54 (95% CI, 0.44 to 0.65); SOFA score, 0.74 (95% CI, 0.64 to 0.83); and APACHE II score, 0.62 (95% CI, 0.51 to 0.73).