Profile of Blood Biomarkers in Febrile Infants Under 90 Days Old With Invasive Bacterial Infection by Type of Infection and Causing Bacteria: A Multicenter Study

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Abstract
Introduction: Early identification of invasive bacterial infections (IBI) in febrile infants under 90 days is essential, with blood biomarkers widely used for their risk evaluation. However, their diagnostic performance may vary by causative organism or type of IBI. Methods: We conducted a retrospective, multicenter study of infants ≤90 days with IBI treated in pediatric emergency departments of 18 hospitals (Spain and Latin America) from 2008 to 2022. IBI was defined by isolation or polymerase chain reaction (PCR) detection of a pathogenic bacterium in blood or cerebrospinal fluid. Sensitivity of standard biomarker cutoffs was analyzed by pathogen and IBI type, with multivariate regression adjusting for age, sex, temperature, symptom duration and clinical presentation. Results: Of 395 infants, Escherichia coli (45.6%) and Streptococcus agalactiae (25.6%) were the most frequently isolated bacteria, and bacteremia (43.8%) and bacteremic urinary tract infection (41.3%) were the most frequent IBI. Biomarker responses varied by organism and IBI type. E. coli IBIs showed higher white blood cell (WBC) and absolute neutrophil (ANC) counts and C-reactive protein levels than S. agalactiae IBIs. Only procalcitonin had high sensitivity for S. agalactiae IBIs. Standard cutoffs for WBC and ANC showed sensitivities below 50% for all pathogens and types of IBI. Conclusion: Biomarker levels in young febrile infants with IBIs depend on IBI type and causing bacteria. Increases in WBC, ANC and C-reactive protein are lower in isolated bacteremias than in bacteremic urinary tract infections. Procalcitonin is the best biomarker for ruling out S. agalactiae IBIs. These distinctions are key to interpreting lab tests and preventing underdiagnosis of invasive infections.

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