Identifying patients with bacterial infections using a combination of C-reactive protein, procalcitonin, TRAIL, and IP-10 in the emergency department: a prospective observational cohort study.

The aim was to effectively reduce the unnecessary use of broad spectrum antibiotics in the emergency department (ED), patients with bacterial infections need to be identified accurately. We investigated the diagnostic value of a combination of biomarkers for bacterial infections, C-reactive protein (CRP), and procalcitonin (PCT), together with biomarkers for viral infections, tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), and interferon-gamma-induced protein-10 (IP-10), in identifying suspected and confirmed bacterial infections in a general ED population with fever. This is a sub-study in the HiTEMP cohort. Patients with fever were included during ED triage, and blood samples were obtained. Using both diagnostics and expert panel analysis, all patients were classified as having either suspected or confirmed bacterial infections, or non-bacterial disease. Using multivariable logistic regression analysis, three biomarker models were analysed: model 1, CRP, TRAIL, IP-10; model 2, PCT, TRAIL, IP-10; and model 3, CRP, PCT, TRAIL, IP-10. A total of 315 patients were included, of whom 228 patients had a suspected or confirmed bacterial infection. The areas under the curve for the combined models were the following: model 1, 0.730 (95% CI 0.665-0.795); model 2, 0.748 (95% CI 0.685-0.811); and model 3, 0.767(95% CI 0.704-0.829). These findings show that a combination of CRP, PCT, TRAIL and IP-10 can identify bacterial infections with higher accuracy than single biomarkers and combinations of a single bacterial biomarkers combined with TRAIL and IP-10.

van der Does Y ，Rood PPM ，Ramakers C ，Schuit SCE ，Patka P ，van Gorp ECM ，Limper M ... -  《-》

A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study.

Ashkenazi-Hoffnung L ，Oved K ，Navon R ，Friedman T ，Boico O ，Paz M ，Kronenfeld G ，Etshtein L ，Cohen A ，Gottlieb TM ，Eden E ，Chistyakov I ，Srugo I ，Klein A ，Ashkenazi S ，Scheuerman O ... -  《-》

HNL (Human Neutrophil Lipocalin) and a multimarker approach to the distinction between bacterial and viral infections.

The distinction between bacterial and viral causes of acute infections is a major clinical challenge. In this report we investigate the diagnostic performance in this regard of nine candidate biomarkers together with HNL (Human Neutrophil Lipocalin). Blood was obtained from patients with symptoms of infectious (n = 581). HNL was measured in whole blood (B-HNL) after pre-activation with the neutrophil activator fMLP or in plasma (P-HNL). Azurocidin also known as heparin-binding protein (HBP), Calprotectin, PMN-CD64, CRP (C-reactive protein), IP-10 (Interferon γ-induced Protein 10 kDa), PCT (Procalcitonin), TK1 (Thymidine kinase 1), TRAIL (TNF-related apoptosis-inducing ligand) were measured in plasma/serum. Area under the ROC (receiver operating characteristics) curve (AuROC) was used for the evaluation of the clinical performance of the biomarkers. Side-by-side comparisons of the ten biomarkers showed large difference in the AuROC with B-HNL being the superior biomarker (0.91, 95% CI 0.86-0.95) and with the other nine biomarkers varying from AuROC of 0.63-0.79. The combination of B-HNL with IP-10 and/or TRAIL increased the diagnostic performance further to AuROCs of 0.94-0.97. The AuROCs of the combination of CRP with IP-10 and/or TRAIL were significantly lower than combinations with B-HNL 0.87 (95% CI 0.83-0.91). The diagnostic performance of whole blood activated HNL was superior in the distinction between bacterial or viral infections. The addition of IP-10 and/or TRAIL to the diagnostic algorithm increased the performance of B-HNL further. The rapid analysis of HNL, reflecting bacterial infections, together with biomarkers reflecting viral infections may be the ideal combination of diagnostic biomarkers of acute infections.

Venge P ，Eriksson AK ，Holmgren S ，Douhan-Håkansson L ，Peterson C ，Xu S ，Eriksson S ，Garwicz D ，Larsson A ，Pauksen K ... -  《-》

C-reactive protein, procalcitonin and the lab-score for detecting serious bacterial infections in febrile children at the emergency department: a prospective observational study.

Nijman RG ，Moll HA ，Smit FJ ，Gervaix A ，Weerkamp F ，Vergouwe Y ，de Rijke YB ，Oostenbrink R ... -  《-》

Procalcitonin-guided antibiotic therapy in patients with fever in a general emergency department population: a multicentre non-inferiority randomized clinical trial (HiTEMP study).

Overuse of broad-spectrum antibiotics in emergency departments (EDs) results in antibiotic resistance. We determined whether procalcitonin (PCT) -guided therapy can be used to reduce antibiotic regimens in EDs by investigating efficacy, safety and accuracy. This was a non-inferiority multicentre randomized clinical trial, performed in two Dutch hospitals. Adult patients with fever ≥38.2°C (100.8°F) in triage were randomized between standard diagnostic workup (control group) and PCT-guided therapy, defined as standard workup with the addition of one single PCT measurement. The treatment algorithm encouraged withholding antibiotic regimens with PCT <0.5 μg/L, and starting antibiotic regimens at PCT ≥0.5 μg/L. Exclusion criteria were immunocompromised conditions, pregnancy, moribund patients, patients <72 h after surgery or requiring primary surgical intervention. Primary outcomes were efficacy, defined as number of prescribed antibiotic regimens; safety, defined as combined safety end point consisting of 30 days mortality, intensive-care unit admission, ED return visit within 2 weeks; accuracy, defined as sensitivity, specificity and area-under-the-curve (AUC) of PCT for bacterial infections. Non-inferiority margin for safety outcome was 7.5%. Between August 2014 and January 2017, 551 individuals were included. In the PCT-guided group (n = 275) 200 (73%) patients were prescribed antibiotic regimens, in the control group (n = 276) 212 (77%) patients were prescribed antibiotics (p 0.28). There was no significant difference in combined safety end point between the PCT-guided group, 29 (11%), and control group, 46 (16%) (p 0.16), with a non-inferiority margin of 0.46% (n = 526). AUC for confirmed bacterial infections for PCT was 0.681 (95% CI 0.633-0.730), and for CRP was 0.619 (95% CI 0.569-0.669). PCT-guided therapy was non-inferior in terms of safety, but did not reduce prescription of antibiotic regimens in an ED population with fever. In this heterogeneous population, the accuracy of PCT in diagnosing bacterial infections was poor. TRIAL REGISTRATION IN NETHERLANDS TRIAL REGISTER: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=4949.

van der Does Y ，Limper M ，Jie KE ，Schuit SCE ，Jansen H ，Pernot N ，van Rosmalen J ，Poley MJ ，Ramakers C ，Patka P ，van Gorp ECM ，Rood PPM ... -  《-》