Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young Febrile Children: A Double-Blind, Multicentre, Observational Study - Archive ouverte HAL Access content directly
Journal Articles Journal of Clinical Medicine Year : 2022

Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young Febrile Children: A Double-Blind, Multicentre, Observational Study

Aurélie Portefaix
  • Function : Author
Sylvie Pons
Antoine Ouziel
  • Function : Author
Philippe Rebaud
  • Function : Author
Marie-Caroline Delafay
  • Function : Author
Laurence Generenaz
  • Function : Author
Guy Oriol
  • Function : Author
Boris Meunier
  • Function : Author
Fatima Abbas-Chorfa
  • Function : Author
Sophie Trouillet-Assant
  • Function : Author
Tiphanie Ginhoux
  • Function : Author
Yves Gillet
  • Function : Author
Karen Brengel-Pesce
Etienne Javouhey
  • Function : Author

Abstract

The diagnosis of serious bacterial infection (SBI) in young febrile children remains challenging. This prospective, multicentre, observational study aimed to identify new protein marker combinations that can differentiate a bacterial infection from a viral infection in 983 children, aged 7 days–36 months, presenting with a suspected SBI at three French paediatric emergency departments. The blood levels of seven protein markers (CRP, PCT, IL-6, NGAL, MxA, TRAIL, IP-10) were measured at enrolment. The patients received the standard of care, blinded to the biomarker results. An independent adjudication committee assigned a bacterial vs. viral infection diagnosis based on clinical data, blinded to the biomarker results. Computational modelling was applied to the blood levels of the biomarkers using independent training and validation cohorts. Model performances (area under the curve (AUC), positive and negative likelihood ratios (LR+ and LR–)) were calculated and compared to those of the routine biomarkers CRP and PCT. The targeted performance for added value over CRP or PCT was LR+ ≥ 5.67 and LR− ≤ 0.5. Out of 652 analysed patients, several marker combinations outperformed CRP and PCT, although none achieved the targeted performance criteria in the 7 days–36 months population. The models seemed to perform better in younger (7–91 day-old) patients, with the CRP/MxA/TRAIL combination performing best (AUC 0.895, LR+ 10.46, LR− 0.16). Although computational modelling using combinations of bacterial- and viral-induced host-protein markers is promising, further optimisation is necessary to improve SBI diagnosis in young febrile children.

Dates and versions

hal-04179588 , version 1 (10-08-2023)

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Aurélie Portefaix, Sylvie Pons, Antoine Ouziel, Romain Basmaci, Philippe Rebaud, et al.. Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young Febrile Children: A Double-Blind, Multicentre, Observational Study. Journal of Clinical Medicine, 2022, 11 (21), pp.6563. ⟨10.3390/jcm11216563⟩. ⟨hal-04179588⟩
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