Journal of Infection (2014) 69, 627e632
www.elsevierhealth.com/journals/jinf
LETTERS TO THE EDITOR Diagnostic and prognostic potential of presepsin in Emergency Department patients presenting with systemic inflammatory response syndrome
Dear Sir, We read with interest the paper by ten Oever et al. who evaluated a number of biomarkers for the discrimination between bacterial and viral lower respiratory tract infections.1 C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) are widely used in clinical routine as biomarkers in infectious and inflammatory conditions. PCT is considered the most promising biomarker in this field and has demonstrated superior diagnostic accuracy for bloodstream infection (BSI) when compared to other biomarkers.2,3 However, normal PCT levels below 0.5 ng/L and even below 0.1 ng/L have been reported in systemic inflammatory response syndrome (SIRS) patients with BSI.4 Presepsin is a new and promising biomarker for early detection of bacterial sepsis.5,6 To date, few studies evaluated the role of presepsin in predicting the presence of bacteremia.7,8 In this semiprospective observational study we assessed diagnostic and prognostic potential of presepsin in SIRS patients with suspected BSI on admission to the Emergency Department (ED). 300 patients were consecutively included between March and October 2012 at the University Hospital of Graz, Austria, until the number of each causative pathogen and negative controls reached each 100 for Gram-positive and Gram-negative bacteremia, 50 for candidemia and 50 for controls (i.e. patients with SIRS but negative blood culture). As Candida spp. were isolated rarely we decided to include additional patients with bacteremia or negative blood culture to reach the anticipated number of 300 patients. Presepsin, PCT, IL-6, and CRP were determined from blood samples collected simultaneously with blood cultures and before initiation of antiinfective therapy, as described previously.3 Presepsin was retrospectively determined from plasma samples that were aliquoted, frozen and stored at 80 C immediately after collection. Analysis was performed at the Institute of Clinical Chemistry and Biochemistry, University Medical Centre of Ljubljana, Slovenia. Presepsin was measured on a PATHFAST Immunoanalyzer system using the commercially available chemiluminescent enzyme immunoassay (Mitsubishi Chemical Europe, Duesseldorf, Germany).
This study was approved by the ethics committee of the Medical University of Graz, Austria (EC-number 21e469 ex 09/10). Statistical analysis was performed using SPSS, version 20 (SPSS Inc., Chicago, IL, USA). Receiver operating characteristics (ROC) curve analysis was performed for biomarkers and combinations. Area under the curve (AUC) values were displayed including 95% confidence interval (CI). Baseline characteristics, mortality rates and blood culture results are presented in Table 1. For presepsin (p Z 0.012), PCT (p < 0.001), and IL-6 (p Z 0.022) significant higher plasma levels were found in patients with BSI. This was not the case for CRP (p Z 0.051). ROC curve analysis revealed AUCs of 0.605 (95%CI 0.522e0.688) for presepsin, 0.687 (95%CI 0.612e0.763) for PCT, 0.599 (95%CI 0.519e0.678) for IL-6 and 0.582 (95%CI 0.498e0.667) for CRP for prediction of BSI. Detailed results of biomarker levels related to BSI caused by different pathogens are depicted in Table 2. The potential of the four biomarkers for prediction of bacteremia revealed AUCs of 0.6 (95%CI 0.517e0.684) for presepsin, 0.693 (0.617e0.768) for PCT, 0.604 (0.524e0.685) for IL-6 and 0.586 (0.502e0.670) for CRP. Only PCT showed a significant difference between Gram-positive and Gram-negative blood culture results with higher levels in the latter (p Z 0.008). When the two most frequent causes of BSI Staphylococcus aureus and Escherichia coli were compared no significant differences were found for either of the parameters. Presepsin was significantly higher (p Z 0.038) in patients with candidemia compared to patients with negative blood culture results. ROC curve analyses revealed an AUC for presepsin of 0.7 (95%CI 0.539e0.86), PCT 0.652 (0.487e0.816), IL-6 0.505 (0.31e0.7) and CRP 0.553 (0.401e0.705) for differentiation between candidemia and negative blood culture. ROC curve analysis for prediction of ICU admission, 48 h-, 30-day- and 90-day mortality, revealed the following AUCs: 0.645 (95%CI 0.565e0.725), 0.619 (0.442e0.795), 0.65 (0.557e0.742) and 0.659 (0.581e0.737) for presepsin; 0.612 (95%CI 0.529e0.694), 0.709 (0.557e0.861), 0.583 (0.497e0.668) and 0.577 (0.502e0.653) for PCT; 0.597 (95% CI 0.506e0.689), 0.685 (0.532e0.838), 0.547 (0.445e0.648) and 0.516 (0.429e0.603) for IL-6; 0.561 (95%CI 0.487e0.634), 0.61 (0.476e0.744), 0.583 (0.501e0.665) and 0.574 (0.501e0.647) for CRP. Cut-off values for presepsin regarding 30-day mortality were calculated with Youdens index, revealing a cut-off of 1379 pg/mL with a sensitivity of 56%, and a specificity of 63%. Diagnostic potential of presepsin was markedly lower when compared to previous studies that reported AUCs of
628 Table 1
Letters to the Editor Baseline characteristics, mortality rates and blood culture results and of the study population (n Z 300).
n Age e years (mean ± SD) Female sex e no. (%) Underlying conditions e no. (%) Cardiovascular disease Malignancies Hematological disease Neutropenia (
www.elsevierhealth.com/journals/jinf
LETTERS TO THE EDITOR Diagnostic and prognostic potential of presepsin in Emergency Department patients presenting with systemic inflammatory response syndrome
Dear Sir, We read with interest the paper by ten Oever et al. who evaluated a number of biomarkers for the discrimination between bacterial and viral lower respiratory tract infections.1 C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) are widely used in clinical routine as biomarkers in infectious and inflammatory conditions. PCT is considered the most promising biomarker in this field and has demonstrated superior diagnostic accuracy for bloodstream infection (BSI) when compared to other biomarkers.2,3 However, normal PCT levels below 0.5 ng/L and even below 0.1 ng/L have been reported in systemic inflammatory response syndrome (SIRS) patients with BSI.4 Presepsin is a new and promising biomarker for early detection of bacterial sepsis.5,6 To date, few studies evaluated the role of presepsin in predicting the presence of bacteremia.7,8 In this semiprospective observational study we assessed diagnostic and prognostic potential of presepsin in SIRS patients with suspected BSI on admission to the Emergency Department (ED). 300 patients were consecutively included between March and October 2012 at the University Hospital of Graz, Austria, until the number of each causative pathogen and negative controls reached each 100 for Gram-positive and Gram-negative bacteremia, 50 for candidemia and 50 for controls (i.e. patients with SIRS but negative blood culture). As Candida spp. were isolated rarely we decided to include additional patients with bacteremia or negative blood culture to reach the anticipated number of 300 patients. Presepsin, PCT, IL-6, and CRP were determined from blood samples collected simultaneously with blood cultures and before initiation of antiinfective therapy, as described previously.3 Presepsin was retrospectively determined from plasma samples that were aliquoted, frozen and stored at 80 C immediately after collection. Analysis was performed at the Institute of Clinical Chemistry and Biochemistry, University Medical Centre of Ljubljana, Slovenia. Presepsin was measured on a PATHFAST Immunoanalyzer system using the commercially available chemiluminescent enzyme immunoassay (Mitsubishi Chemical Europe, Duesseldorf, Germany).
This study was approved by the ethics committee of the Medical University of Graz, Austria (EC-number 21e469 ex 09/10). Statistical analysis was performed using SPSS, version 20 (SPSS Inc., Chicago, IL, USA). Receiver operating characteristics (ROC) curve analysis was performed for biomarkers and combinations. Area under the curve (AUC) values were displayed including 95% confidence interval (CI). Baseline characteristics, mortality rates and blood culture results are presented in Table 1. For presepsin (p Z 0.012), PCT (p < 0.001), and IL-6 (p Z 0.022) significant higher plasma levels were found in patients with BSI. This was not the case for CRP (p Z 0.051). ROC curve analysis revealed AUCs of 0.605 (95%CI 0.522e0.688) for presepsin, 0.687 (95%CI 0.612e0.763) for PCT, 0.599 (95%CI 0.519e0.678) for IL-6 and 0.582 (95%CI 0.498e0.667) for CRP for prediction of BSI. Detailed results of biomarker levels related to BSI caused by different pathogens are depicted in Table 2. The potential of the four biomarkers for prediction of bacteremia revealed AUCs of 0.6 (95%CI 0.517e0.684) for presepsin, 0.693 (0.617e0.768) for PCT, 0.604 (0.524e0.685) for IL-6 and 0.586 (0.502e0.670) for CRP. Only PCT showed a significant difference between Gram-positive and Gram-negative blood culture results with higher levels in the latter (p Z 0.008). When the two most frequent causes of BSI Staphylococcus aureus and Escherichia coli were compared no significant differences were found for either of the parameters. Presepsin was significantly higher (p Z 0.038) in patients with candidemia compared to patients with negative blood culture results. ROC curve analyses revealed an AUC for presepsin of 0.7 (95%CI 0.539e0.86), PCT 0.652 (0.487e0.816), IL-6 0.505 (0.31e0.7) and CRP 0.553 (0.401e0.705) for differentiation between candidemia and negative blood culture. ROC curve analysis for prediction of ICU admission, 48 h-, 30-day- and 90-day mortality, revealed the following AUCs: 0.645 (95%CI 0.565e0.725), 0.619 (0.442e0.795), 0.65 (0.557e0.742) and 0.659 (0.581e0.737) for presepsin; 0.612 (95%CI 0.529e0.694), 0.709 (0.557e0.861), 0.583 (0.497e0.668) and 0.577 (0.502e0.653) for PCT; 0.597 (95% CI 0.506e0.689), 0.685 (0.532e0.838), 0.547 (0.445e0.648) and 0.516 (0.429e0.603) for IL-6; 0.561 (95%CI 0.487e0.634), 0.61 (0.476e0.744), 0.583 (0.501e0.665) and 0.574 (0.501e0.647) for CRP. Cut-off values for presepsin regarding 30-day mortality were calculated with Youdens index, revealing a cut-off of 1379 pg/mL with a sensitivity of 56%, and a specificity of 63%. Diagnostic potential of presepsin was markedly lower when compared to previous studies that reported AUCs of
628 Table 1
Letters to the Editor Baseline characteristics, mortality rates and blood culture results and of the study population (n Z 300).
n Age e years (mean ± SD) Female sex e no. (%) Underlying conditions e no. (%) Cardiovascular disease Malignancies Hematological disease Neutropenia (
