Validation of Biomarkers Performance to Reduce Antibiotics overUse in newBorns With Suspected Clinical Signs of InfectionS

Study Overview
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Brief Summary
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Late-onset neonatal sepsis (LOS), occurring in newborn of at least 7 days of life, is frequently observed in Neonatal Intensive Care Units (NICUs) and potentially severe (mortality, neurologic and respiratory impairments). Despite its high prevalence, a reliable diagnostic remains difficult. Currently, nonspecific clinical signs that might be related to other neonatal conditions such as prematurity and birth defects, are used to determine the diagnosis of LOS. Laboratory results of biological markers, such as C-Reactive Protein (CRP) and Procalcitonin (PCT) are often delayed in comparison with LOS onset. Blood culture results are too late and lack sensitivity. This explains why excessive antibiotic use is observed in a large proportion of NICU hospitalized newborns. This results in an increased antibiotic resistance, microbiota modification, neonatal complications (pulmonary, ophthalmologic and neurologic) and mortality. A previous study (EMERAUDE) aimed to identify new biomarkers to early exclude the diagnosis of LOS, in order to limit antibiotic overuse. This study including 230 neonates revealed high performances of IL6, IL10, NGAL and combinations of PCT/IL10 and PTX3/NGAL. The main objective of the present study will be to validate the performances of these biomarkers in another cohort. The secondary objectives will be to explore transcriptomic biomarkers and salivary biomarkers.

Official Title
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Validation of Biomarkers Performance to Reduce Antibiotics overUse in newBorns With Suspected Clinical Signs of InfectionS

Conditions
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Neonatal Late Onset Sepsis

Intervention / Treatment
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* Diagnostic Test: Newborns suspected of Infections


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient hospitalized in the NICU of one of the two recruiting centers at the time of inclusion Patients aged ≥ 7 days Patients weighted ≥ 500 g the day of blood sample patients with suggestive signs of LOS including at least one of the following:Fever > 38°C; tachycardia > 160bpm; capillary refill time > 3 seconds; grey and/or pale skin complexion; apnea/ bradycardia syndrome, bloating; vomiting; rectal bleeding; hypotonia; lethargy; seizures without other obvious cause; increased ventilatory support and/or increased FiO2; cutaneous rash; inflammation at the needle-puncture site of the central venous catheter; or any other condition for which the clinician suspected an infection patients with a standard of care blood sampling, including at least a blood culture; Exclusion Criteria: Patient treated with antibiotics for a bacteriologically confirmed infection at the time of sampling or within 48 hours prior to sampling Patient who underwent surgery within the previous 7 days Patients vaccinated within the previous 7 days Patient who received treatment with systemic corticosteroid therapy in the 48 hours prior to sampling Patient with severe combined immunodeficiency Opposition from parent(s)/guardian(s)

Ages Eligible for Study
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Minimum Age: 7 Days
Maximum Age: 14 Days

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

| Intervention/Treatment |
| --- |
|Diagnostic Test: Newborns suspected of Infections|This study will include NICU newborns of at least 7 days of life with suggestive signs of neonatal sepsis. The results will be extrapolated to this same population.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of late onset sepsis | The primary outcome measure will be determined by an independent adjudication committee that will classify the patients into the following categories : infection, non infected or undetermined. This committee will be blinded to the biomarkers of the study. It will be composed of two neonatologists and a pediatrician specialized in pediatric infectious diseases. The diagnostic performance of the biomarkers combination will be based on the adjudication committee classification (gold standard). | 72 hours maximum after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neonatal sepsis,, biomarker, diagnostic,, antibiotic use, preterm neonates, NICU