Diagnostic Accuracy of Procalcitonin in Bacterial Infections of the CNS: An Updated Systematic Review, Meta-Analysis, and Meta-Regression*

OBJECTIVES: To evaluate diagnostic accuracy of serum and cerebrospinal fluid (CSF) procalcitonin for diagnosing CNS bacterial infections. DATA SOURCES: We searched MEDLINE, Cochrane Central Register of Controlled Trials, and International Web of Science databases from January 1, 2016, to September 30, 2022. STUDY SELECTION: Randomized controlled trials and observational studies, either prospective or retrospective, focusing on procalcitonin as a biomarker for CNS infections. DATA EXTRACTION: We screened and extracted studies independently and in duplicate. We assessed risk of bias using the revised Quality Assessment for Studies of Diagnostic Accuracy tool. Data for diagnostic sensitivity and specificity were pooled using the bivariate or hierarchical model, as appropriate. DATA SYNTHESIS: Of 5,347 citations identified, 23 studies were included. Overall, CSF procalcitonin showed slightly higher pooled sensitivity, specificity, and positive likelihood ratio compared with serum procalcitonin. In adults, pooled sensitivity of CSF procalcitonin was 0.89 (95% CI, 0.71–0.96), specificity 0.81 (95% CI, 0.66–0.91); pooled sensitivity of serum procalcitonin was 0.82 (95% CI, 0.58–0.94), specificity 0.77 (95% CI, 0.60–0.89). In children, pooled sensitivity of CSF procalcitonin was 0.96 (95% CI, 0.88–0.99), specificity 0.91 (95% CI, 0.72–0.97); pooled sensitivity of serum procalcitonin was 0.90 (95% CI, 0.75–0.97), specificity 0.83 (95% CI, 0.67–0.92). In post-neurosurgical patients, pooled sensitivity of CSF procalcitonin was 0.82 (95% CI, 0.53–0.95), specificity 0.81 (95% CI, 0.63–0.91); pooled sensitivity of serum procalcitonin was 0.65 (95% CI, 0.33–0.88), specificity 0.61 (95% CI, 0.41–0.78). Logistic regression revealed between-study heterogeneity higher for serum than CSF procalcitonin. For the latter, threshold variability was found as source of heterogeneity. CONCLUSIONS: In children and critical post-neurosurgical patients, CSF procalcitonin gains superior sensitivity and specificity compared with serum procalcitonin. Overall, CSF procalcitonin appears to have a higher pooled positive likelihood ratio compared with serum procalcitonin.