Candidate Biomarkers for the Detection of Serious Infections in Children: A Prospective Clinical Study

Abstract

BACKGROUND: Serious bacterial infections (SBI) in children are still associated with considerable morbidity and mortality. Early identification of SBI in children presenting with fever and/or signs of systemic inflammatory response (SIRS) remains challenging, as clinical presentation may be subtle, and the role of laboratory markers is still debated. The purpose of the present study is to evaluate the diagnostic role of established and candidate blood biomarkers for the early discrimination of SBI in pediatric patients presenting with fever and/or SIRS criteria.METHODS: Children who met SIRS criteria and had the clinical indication to perform blood sampling at the first medical evaluation were consecutively enrolled. A panel of biomarkers was performed at enrolment, including C-reactive protein, procalcitonin, white blood cell count (WBC), absolute neutrophil count (ANC), interleukin (IL)-6, IL-8, IL-10, human terminal complement complex (C5b-9), Plasmalemma-Vesicle-associated protein 1 (PV-1), Intercellular Adhesion Molecule-1 (ICAM-1), and Phospholipase A2 (PLA2). Bivariate logistic regression models were created to identify significant predictors of SBI. RESULTS: Among 103 patients (median age 2.9 years, 60% males), 39 had a diagnosis of SBI (38%). Significant predictors of SBI were CRP (p=0.001) and ICAM-1 (p=0.043). In the subgroup of patients who were not immunocompromised because of a pre-existing medical condition or therapy (e.g. children with cancer and chemotherapy-induced neutropenia), significant predictors of SBI, were CRP (p=0.001) and ICAM-1 (p=0.037), WBC (p=0.035), ANC (p=0.012) and ANC/WBC ratio (p=0.015). The diagnostic performance of each variable as evaluated by means of ROC curves revealed suboptimal performance for all variables. A model combining CRP and ANC/WBC ratio, however, had a greater diagnostic accuracy than each one of the two variables. CONCLUSION: This study confirmed the limited usefulness of blood biomarkers for early diagnosis of SBI. WBC, ANC, ANC/WBC ratio, CRP and ICAM-1 showed the best, albeit moderate, diagnostic accuracy as single marker. At present, clinical judgement remains the mainstay for the diagnosis of SBIs in children.