ReviewFrontiers in pediatrics2026
Identifying the thresholds of C-reactive protein, procalcitonin, and interleukin-6 among children ≤36 months' old with fever without source at risk of serious bacterial infections: a systematic review and meta-analysis.
Review in Frontiers in pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Management of children ≤36 months of age presenting with fever without source remains a challenge because the underlying aetiologies may range from self-limiting viral infections to serious bacterial infections (SBIs) including bacteraemia, urinary tract infection (UTI), pneumonia, bacterial meningitis, osteomyelitis, or septic arthritis. This systematic review was conducted to determine the thresholds at which C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) can predict SBIs in this population. Methods: We systematically searched electronic databases such as MEDLINE, Cochrane, CINAHL, and Web of Science for studies that evaluated the diagnostic accuracies of CRP, PCT, and IL-6 in detecting SBIs in children ≤36 months of age presenting with fever without source, during the period between November 2013 and November 2023. Area under the summary receiver operating curve (SROC) was calculated by the Rutter and Gatsonis method. Results: Datasets from 37 studies were included. A CRP cut-off of 10-20 mg/L had the highest pooled sensitivity of 0.75 (95% CI: 0.54-0.89), while a CRP cut-off of >40 mg/L had the highest pooled specificity 0.92 (95% CI: 0.87-0.95). A PCT cut-off of <0.5 ng/mL had the highest pooled sensitivity of 0.7812 (95% CI: 0.59-0.90) but the lowest pooled specificity of 0.69 (95% CI: 0.54-0.81). Based on receiver operating curve (ROC) analysis, a CRP cut-off between 10 and 20 mg/L and a PCT cut-off of <0.5 ng/mL showed the best diagnostic performance with a pooled AUC of 0.84 (95% CI: 0.79-0.90) and 0.816 (95% CI: 0.727-0.928), respectively. Only 1 study for IL-6 reported that a threshold of 20 pg/dL had a sensitivity and specificity of 79.1% and 91.6%, respectively. Conclusion: A PCT cut-off of 0.5 ng/mL and a CRP cut-off of 10-20 mg/L display the best performance in identifying SBIs in children ≤36 months of age with fever without source. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023439093, identifier CRD42023439093.
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