Infections, Infections - Bacterial, Sepsis, Viral Infection
Conditions
Keywords
Sepsis, Emergency department, Early diagnosis of sepsis, Human neutrophil lipocalin, Biomarker, HNL
Brief summary
The aim of this study is to improve the medical care of patients with infections for which the cause cannot be clearly identified as bacterial or viral. To achieve this, we are investigating a new inflammatory marker in the blood that may help identify severe bacterial infections more quickly. Early detection is important to prevent complications and ensure that patients receive the most appropriate treatment as soon as possible. This is an observational study. The knowledge gained from this study may help improve the care of patients with infections of unclear origin by supporting faster diagnosis, earlier treatment, improved risk assessment, and better planning of follow-up care.
Detailed description
This observational study evaluates the diagnostic and prognostic value of Human Neutrophil Lipocalin (HNL) in patients presenting to the Emergency Department (ED) with suspected infection. Early identification of bacterial infection and sepsis remains a major challenge in emergency care due to the heterogeneity of clinical presentations and the lack of highly accurate diagnostic tools. In particular, distinguishing patients at low risk from those at risk of clinical deterioration is crucial for appropriate treatment decisions, triage, and disposition planning. Delayed recognition of bacterial infection and sepsis is associated with adverse outcomes, especially in patients with atypical presentations. HNL has emerged as a promising biomarker for differentiating bacterial from viral infections. Previous studies have demonstrated a high diagnostic accuracy of HNL, with reported sensitivity and specificity exceeding 90%, potentially outperforming routinely used biomarkers such as white blood cell count (WBC) and C-reactive protein (CRP). A rapid and reliable biomarker for identifying bacterial infection could support earlier diagnosis, optimize patient management, reduce progression to sepsis, and contribute to more appropriate antibiotic use. The primary objective of this study is to assess the diagnostic performance of HNL for the detection of bacterial infection in ED patients and to compare its accuracy with routinely used biomarkers, including WBC, CRP, and procalcitonin (PCT). Secondary objectives include: Comparing the diagnostic performance of HNL measured in serum versus activated Li-heparin whole blood. Evaluating factors that may influence the predictive value of HNL, including age, sex, comorbidities, immunosuppression, and antibiotic treatment. Assessing the prognostic value of HNL for 30-day mortality and comparing its performance with serum lactate, an established predictor of adverse outcomes. The results of this study may contribute to improved risk stratification and clinical decision-making in patients presenting to the ED with suspected infection.
Interventions
None listed
Sponsors
University Hospital, Basel, Switzerland
Clinical Trial Unit, University Hospital Basel, Switzerland
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adults presenting to the Emergency Department with suspected infection * Written informed consent provided prior to enrolment * Evidence of significant physiological disturbance, defined by abnormal vital signs requiring further medical assessment * Symptoms suggestive of a respiratory tract infection (e.g. cough with sputum, worsening cough, or breathing difficulties) * Symptoms suggestive of a urinary tract infection (e.g. pain during urination, frequent urination, or urgency) * Pain, redness, warmth, or discharge at the site of a vascular catheter or intravenous line * Signs of a skin or soft tissue infection, including pain, tenderness, swelling, redness, warmth, or pus formation * Nausea, vomiting, abdominal pain, or jaundice suggestive of a possible abdominal infection * Headache, neck stiffness, or other symptoms suggestive of a central nervous system infection * Abnormal vital signs corresponding to a National Early Warning Score (NEWS) of ≥3 points
Exclusion criteria
* Known pregnancy at the time of study enrolment * Antibiotic treatment that started more than 24 hours before presentation to the Emergency Department * Inability or unwillingness to provide written informed consent for study participation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Receiver Operating Characteristic Curve (AUROC) for bacterial infection | Baseline blood sample; diagnosis adjudicated after completion of follow-up (up to 30 days) | Diagnostic performance of HNL, WBC, CRP and PCT measured in venous blood samples collected at Emergency Department screening for identifying bacterial infection. Final infection classification (bacterial, viral, other infection, or no infection) will be determined by an independent adjudication committee based on clinical records, laboratory results and microbiological findings. |
| Sensitivity for bacterial infection | Baseline blood sample; diagnosis adjudicated after completion of follow-up (up to 30 days) | Sensitivity of HNL, WBC, CRP and PCT for identifying bacterial infection using the adjudicated infection diagnosis as the reference standard. |
| Specificity for sepsis and septic shock | Baseline blood sample; diagnosis adjudicated after completion of follow-up (up to 30 days) | Specificity of HNL, WBC, CRP and PCT for identifying sepsis and septic shock using adjudicated Sepsis-3 diagnoses as the reference standard. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30-day mortality | 30 days after enrolment | Death from any cause within 30 days after enrolment, assessed through follow-up contact with the patient's general practitioner, the patient or a relative, or other available sources. |
| Cause of death | 30 days after enrolment | Cause of death among participants who die during the 30-day follow-up period. |
| Hospital re-presentation | 30 days after enrolment | Re-presentation to hospital occurring within 30 days after enrolment. |
| Length of hospital stay (LOS) | From hospital admission to discharge, assessed up to 30 days after enrolment | Length of hospital stay for the index presentation, measured in days from admission to discharge. |
| Mortality in Emergency Department Sepsis (MEDS) score | Baseline (at Emergency Department presentation) | Mortality in Emergency Department Sepsis (MEDS) score is a clinical risk stratification tool used to estimate the risk of mortality in patients with sepsis presenting to the emergency department. The total score ranges from 0 to 27 points, with higher scores indicating a greater predicted risk of death and a worse clinical prognosis. |
| Sequential Organ Failure Assessment (SOFA) score | Baseline (at Emergency Department presentation) | Sequential Organ Failure Assessment (SOFA) score is used to assess the extent of organ dysfunction across six organ systems (respiratory, cardiovascular, hepatic, coagulation, renal, and neurological). Total scores range from 0 to 24, with higher scores indicating more severe organ dysfunction and a worse clinical condition. |
| Quick Sequential Organ Failure Assessment (qSOFA) score | Baseline (at Emergency Department presentation) | The Quick Sequential Organ Failure Assessment (qSOFA) score is a bedside screening tool used to identify patients with suspected infection who are at increased risk of poor outcomes. The total score ranges from 0 to 3 points, based on altered mental status, systolic blood pressure ≤100 mmHg, and respiratory rate ≥22 breaths per minute. Higher scores indicate a greater risk of adverse outcomes and a worse clinical prognosis. |
Countries
Switzerland
Contacts
PRINCIPAL_INVESTIGATORRoland Bingisser
Prof. Dr. med.
Outcome results
None listed