A Novel Framework for Phenotyping Children With Suspected or Confirmed Infection for Future Biomarker Studies

Background: The limited diagnostic accuracy of biomarkers in children at risk a serious bacterial infection (SBI) might be due to the imperfect reference standard SBI. We aimed evaluate performance new classification algorithm for biomarker discovery Methods: used data from five previously published, prospective observational studies, which included patients aged 0– <16 years: Alder Hey emergency department ( n = 1,120), pediatric intensive care unit 355), Erasmus 1,993), Maasstad 714) and St. Mary's hospital 200) cohorts. Biomarkers including procalcitonin (PCT) (4 cohorts), neutrophil gelatinase-associated lipocalin-2 (NGAL) (3 cohorts) resistin (2 were compared their ability classify according current standards (dichotomous SBI vs. non-SBI), proposed PERFORM that assign one eleven categories. These categories based on clinical phenotype, test outcomes C-reactive protein level accounted uncertainty final diagnosis many febrile children. success was measured by Area under receiver operating Curves (AUCs) when they individually or combination. Results: Using system, with clinically confident (“definite bacterial” category) had significantly higher levels PCT, NGAL those viral viral” category). Patients concentrations varied across spectrum. AUCs “definite following than using “SBI” “non-SBI” classification; summary AUC PCT 0.77 (95% CI 0.72–0.82) 0.70 0.65–0.75); this 0.80 0.69–0.91) 0.58–0.81); 0.68 0.61–0.75) 0.64 (0.58–0.69) three combined 0.83 (0.77–0.89) infections 0.71 (0.67–0.74) “non-SBI.” Conclusion: strongly associated system independent Our provides novel framework phenotyping suspected confirmed future studies.