Fast Assay for Pathogen Identification and Characterization

Study Overview
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Brief Summary
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Sepsis is a life-threatening disease caused by a dysregulated host response to infection. This can lead to organ-dysfunction and septic shock, which is a subset of sepsis where underlying abnormalities increase mortality remarkably. Blood cultures are the gold standard for identifying pathogens in the bloodstream (bacteremia). It is based on cultivation techniques which, theoretically, can detect a single pathogenic cell from a patient sample. However, blood cultures have serious limitations, such as long time to result (3-7 days). This leads to the fact that only a small fraction of the patients obtain a correct diagnosis and in further consequence get the optimal antimicrobial treatment. Patients with sepsis should get antimicrobial treatment within the hour. Thus, physicians start treatment empirically, with broad-spectrum antibiotics. This puts a selective pressure on pathogens and has led to an increased amount of antibiotic resistance. Faster diagnostics are necessary to ensure an immediate and targeted treatment. In the EU-funded FAPIC project, two diagnostic systems that can be used with direct sample material from patients will be developed, avoiding the time-consuming cultivation of pathogens. In this study, the evaluation of the rapid diagnostics will be performed in patients with sepsis, suspected of bacteremia. To this aim, the performance of the diagnostic systems will be evaluated using blood samples that are collected in parallel with blood cultures. In addition, clinical data of the patients will be collected. In routine care, two blood culture sets (2x2 bottles) per patient are collected. One extra blood samples (EDTA, 9 ml) will be sampled with each blood culture set, totaling 2 samples per patient. In this study, patients presenting at the Emergency Department (ED), and the department of infectious diseases/nephrology will be included. The results will be used to estimate the performance, sensitivity, and specificity of the diagnostic systems compared to blood culture. Furthermore, in order to determine the severity of sepsis and to describe the patient population, clinically relevant parameters and laboratory parameters (ferritin, HLA-DR, serum lactate, SOFA score) will be assessed to determine its association with severity of disease and patient mortality. Evaluation will be done exclusively in the lab, and will not be used directly for the diagnosis or management of patients. Standard care will still be provided.

Detailed Description
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This study is a follow-up study of the first prospective study performed in 2017 in the same hospital. The ClinicalTrials.gov ID number of the previous study was NCT03025802.

Official Title
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Fast Assay for Pathogen Identification and Characterization - Prospective Observational Study

Conditions
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Bacteremia, Sepsis, Septic Shock

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients for whom blood cultures are drawn Age ≥ 18 Exclusion Criteria: Age < 18 Patients who are not hospitalized and sent home after ED admission Patients from the haematology department Duplicate blood cultures from the same bacteraemia episode (blood cultures drawn <7 days after first blood culture)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with suspected sepsis<br>Patients for whom blood cultures are drawn at the Emergency Department or the department of Infectious Diseases/Nephrology | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Confirmed bacteremia based on positive blood cultures (SOFA score) | Differences in SOFA score between patients with positive blood cultures and patients with negative blood cultures. SOFA: Sequential Organ Failure Assessment; Range 0-4 (better to worse). | 7 days | 
| Confirmed bacteremia based on positive blood cultures (Serum Lactate) | Differences in Serum Lactate levels between patients with positive blood cultures and patients with negative blood cultures | 7 days | 
| Confirmed bacteremia based on positive blood cultures (Ferritin) | Differences in Ferritin levels between patients with positive blood cultures and patients with negative blood cultures | 7 days | 
| Test performance | Performance characteristics (Clinical sensitivity, specificity and accuracy) of a new rapid diagnostic systems | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Length of Stay (SOFA score) | Differences in length of stay between patients with high and with low SOFA score SOFA: Sequential Organ Failure Assessment; Range 0-4 (better to worse). | 1 year | 
| Length of Stay (Serum Lactate) | Differences in length of stay between patients with high and with low Serum Lactate levels | 1 year | 
| Length of Stay (Ferritin) | Differences in length of stay between patients with high and with low Ferritin levels | 1 year | 
| 30-day Mortality (Sofa score) | Differences in 30-day mortality between patients with high and with low SOFA score SOFA: Sequential Organ Failure Assessment; Range 0-4 (better to worse). | 30 days | 
| 30-day Mortality (Serum Lactate) | Differences 30-day mortality between patients with high and with low Serum Lactate levels | 30 days | 
| 30-day Mortality (Ferritin) | Differences 30-day mortality between patients with high and with low Ferritin levels | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood Cultures