Lipocalin-2 is a Sensitive and Specific Marker of Bacterial Infection in Children

Jethro Herberg; Honglei Huang; Marie L. Thezenas; Victoria Janes; Michael Carter; Stuart Gormley; Melisa S. Hamilton; Benedikt Kessler; Michael Levin; Climent Casals-Pascual

spital NHS Foundation Trust, Southampton, UK. Detailed clinical and laboratory data were recorded. Healthy controls were recruited in out-patients. After excluding patients with proven or possible inflammatory conditions or mycobacterial disease, two independent paediatric infectious disease clinicians with access to all clinical and diagnostic data categorised patients as follows. Children with a clinical syndrome in keeping with SBI (sepsis with shock or severe focal infection) were categorised as 'Definite Bacterial' (DB) only if pathogenic bacteria were detected at a usually sterile site such as blood or CSF, and not including surface swabs, endotracheal secretions or bronchoalveolar lavage samples; otherwise these patients were categorised as 'Probable Bacterial' (PB). Children with a clinical syndrome in keeping with viral infection, not displaying any bacterial features were categorised as 'Definite Viral' (DV) if a matching virus was identified, or otherwise as 'Probable Viral' (PV). Children without detected sterile-site bacteria and with inconclusive clinical features of viral or bacterial infection were classified as 'Uncertains' (U). We set a threshold of 60mg/L for the maximum CRP as a minimum for inclusion into the PB group, or a maximum for inclusion in the PV and DV groups. Inclusion in the DB group was irrespective of CRP. Patients failing the CRP threshold were categorised as 'Uncertain' (U), alongside the other patients in this group with inconclusive clinical features. Controls (C) had no current or recent (previous two weeks) infectious symptoms or immunisations, and no identified or probable chronic infectious or inflammatory conditions. CRP: C-reactive protein. WCC: white cell count Discussion. This study shows that LCN2 is a sensitive and specific biomarker associated with SBI in children with febrile illness and has potential to guide antibiotic treatment decisions. The best diagnostic performance was achieved by combining LCN2 and CRP (AUROC of 0.92).