Biomedicines (Jun 2023)

Performance of 11 Host Biomarkers Alone or in Combination in the Diagnosis of Late-Onset Sepsis in Hospitalized Neonates: The Prospective EMERAUDE Study

  • Sylvie Pons,
  • Sophie Trouillet-Assant,
  • Fabien Subtil,
  • Fatima Abbas-Chorfa,
  • Elise Cornaton,
  • Amélie Berthiot,
  • Sonia Galletti,
  • Aurélie Plat,
  • Stephanie Rapin,
  • Laurene Trapes,
  • Laurence Generenaz,
  • Karen Brengel-Pesce,
  • Arnaud Callies,
  • Franck Plaisant,
  • Olivier Claris,
  • Aurelie Portefaix,
  • Cyril Flamant,
  • Marine Butin

DOI
https://doi.org/10.3390/biomedicines11061703
Journal volume & issue
Vol. 11, no. 6
p. 1703

Abstract

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Despite the high prevalence of late-onset sepsis (LOS) in neonatal intensive care units, a reliable diagnosis remains difficult. This prospective, multicenter cohort study aimed to identify biomarkers early to rule out the diagnosis of LOS in 230 neonates ≥7 days of life with signs of suspected LOS. Blood levels of eleven protein biomarkers (PCT, IL-10, IL-6, NGAL, IP-10, PTX3, CD14, LBP, IL-27, gelsolin, and calprotectin) were measured. Patients received standard of care blinded to biomarker results, and an independent adjudication committee blinded to biomarker results assigned each patient to either infected, not infected, or unclassified groups. Performances of biomarkers were assessed considering a sensitivity of at least 0.898. The adjudication committee classified 22% of patients as infected and all of these received antibiotics. A total of 27% of the not infected group also received antibiotics. The best biomarkers alone were IL-6, IL-10, and NGAL with an area under the curve (95% confidence interval) of 0.864 (0.798–0.929), 0.845 (0.777–0.914), and 0.829 (0.760–0.898), respectively. The best combinations of up to four biomarkers were PCT/IL-10, PTX3/NGAL, and PTX3/NGAL/gelsolin. The best models of biomarkers could have identified not infected patients early on and avoided up to 64% of unjustified antibiotics. At the onset of clinical suspicion of LOS, additional biomarkers could help the clinician in identifying non-infected patients.

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