What question did this study set out to answer?

This review aims to determine the threshold levels of C-reactive protein, procalcitonin, and interleukin-6 for predicting serious bacterial infections in children under 36 months presenting with fever without source.

March 1, 2026Open Access

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

Key Points

This review aims to determine the threshold levels of C-reactive protein, procalcitonin, and interleukin-6 for predicting serious bacterial infections in children under 36 months presenting with fever without source.
Systematic search of studies evaluating CRP, PCT, and IL-6 for serious bacterial infections in children ≤36 months with fever without source.
Analysis included 37 studies published from November 2013 to November 2023.
Calculated area under the summary receiver operating curve for diagnostic accuracy and study heterogeneity.
CRP cut-off at 10–20 mg/L showed the highest sensitivity (0.75) and specificity (0.92 at >40 mg/L).
PCT cut-off at <0.5 ng/mL had sensitivity of 0.78 but lower specificity (0.69).
Best diagnostic performance indicated by pooled AUC of 0.84 for CRP and 0.816 for PCT.

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. I 2 was used to quantify study heterogeneity. All tests were two-sided, and a p -value 0.05 was considered statistically significant. This review was registered with PROSPERO, CRD42023439093. 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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Cite This Study

Sutiman et al. (Thu,) studied this question.

synapsesocial.com/papers/69a3d747ec16d51705d2dba0 https://doi.org/https://doi.org/10.3389/fped.2026.1697210

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