Combination of Leukocyte Cell Surface Biomarkers Measured by Cytometry, to Differentiate Bacterial From Viral Infections in Emergency Department: a Multicentric Cohort for the Validation of Diagnostic Performances

Condition(s) studied

Investigational drug(s) / intervention(s)

2 additional whole blood samples of 6mL each will be taken: As part of the initial blood work-up, 2 additional samples of 6mL each of whole blood will be taken, to which 1mL of Cytodelics® Stabiliser will be added. The tubes will be mixed by inverting 10 to 15 times, incubated at +20°C for 10 minutes, then transported within 1 to 2 hours at 4°C by courier to the CRB at Pitié-Salpêtrière for aliquoting and freezing at -80°C . The expression level of cell surface markers will then be measured in series on an Aurora spectral cytometer, after frozen samples (1 to 2 aliquots) have been sent from the CRB-PSL to CIMI (INSERM U1135) at -80°C approximately once a month. Any remaining samples sent to CIMI will be destroyed once the analyses have been completed.

Study summary

The characterization of the bacterial or viral etiology of an infectious event is required for both isolation decisions and rationale use of antibiotics. In emergency room (ER), the direct identification of the causal pathogen is rarely available in real-time. Alternative is the identification of the host-response to either a bacterial or viral infection. One of this host-response is the expression of peripheral leukocytes cell surface markers, measured by flow cytometry. Investigators and others have reported the high diagnostic performances of combination of cell surface biomarkers to differentiate bacterial from viral infection. The CYTOBACT study aims to confirm on a 500 patients multicentric cohort (200 having already been collected during another study: SEPTIMET), the best combinations for this diagnostic issue.

The study will be conducted in 3 emergency departments of APHP hospitals network in Paris, France. Patients with a suspicion of infection will be proposed to participate. No intervention will be introduced during the routine care in the (ER) which will be let at the discretion of the treating emergency physician. During the routine blood sampling in the ER, an additional 30 ml volume of whole blood will be collected, centrifugated, aliquoted and stored at -80°C for further measurement of the expression of a panel of cell surface markers. The participants will be followed up during their hospitalization (if any) and no longer than 28 days. Clinical data at admission, usual blood tests and all microbiological investigations performed during the hospital stay will be recorded into an electronic case record form (eCRF). Based on all those recorded data (excepted the results of flow cytometry for cell surface biomarkers) 2 independent adjudicators will qualify the infectious episode into bacterial,viral or no infection, and (if any) into infection, sepsis or septic shock (according to Sepsis 3.0 definitions).

Using different "machine learning" statistical tools, all the combination of the cell surface biomarkers will be tested to select those with the highest performance to differentiate bacterial from viral infection.

Eligibility

Primary outcome measure(s)

• performances of cell surface markers combinations for diagnosis — through study completion, an average of 15 months
  area under the ROC curve of the different combinations of cell surface biomarkers for the diagnosis of bacterial or viral infection.

Trial sites (3)

More Assistance Publique - Hôpitaux de Paris trials in France