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To assess the value of procalcitonin (PCT) and C-reactive protein (CRP), compared with that of total white-blood cell count (WBC) and absolute neutrophil count (ANC), in predicting severe bacterial infections (SBIs) in febrile children admitted to Emergency Department.A prospective study was conducted in 408 children aged 7-days to 36-months, admitted with fever without source, at a tertiary care Pediatric Emergency Department. PCT, CRP, WBC, and ANC were determined upon admission and compared. Specificity, sensitivity, multilevel likelihood ratios, receiver operating characteristic (ROC) analysis, and multivariate stepwise logistic regression were carried out.SBI was diagnosed in 94 children (23.1%). PCT, CRP, WBC, and ANC were significantly higher in this group than in non-SBI patients. The area under the ROC (AUC) obtained was 0.82 (95% CI: 0.78–0.86) for PCT, 0.85 (95% CI: 0.81–0.88) for CRP (P = 0.358), 0.71 (95% CI: 0.66–0.75) for WBC, and 0.74 (95% CI: 0.70–0.78) for ANC. Only PCT (OR: 1.32; 95% CI: 1.11–1.57; P < 0.001) and CRP (OR: 1.02; 95% CI: 1.01–1.03; P < 0.001) were retained as significant predictors of SBI in a multiple regression model. For infants with fever <8 hours (n = 45), AUC for PCT and CRP were 0.92 (95% CI: 0.80–0.98) and 0.75 (95% CI: 0.60–0.87), respectively (P = 0.056).Both PCT and CRP are valuable markers in predicting SBI in children with fever without source and they perform better than WBC and ANC. PCT appears more accurate at the beginning of infections, but overall CRP may be the most convenient marker for its better sensitivity and feasibility.