A new study has validated the use of C-reactive protein levels in cerebrospinal fluid as a reliable tool for diagnosing bacterial meningitis in both pediatric and adult patients.
Researchers evaluated the novel method across three European patient groups and found that C-reaction protein (CRP) in cerebrospinal fluid (CSF) helped identify bacterial meningitis with high sensitivity—even when traditional markers like CSF leukocyte count were normal.
CRP is a liver-produced protein that rises in response to inflammation. While commonly measured in blood to detect infection, the researchers assessed CRP levels directly in CSF collected during lumbar puncture. A CRP level of 0.3 mg/L or higher in CSF was considered a positive result.
A total of 260 patients with suspected central nervous system infections were included: 103 adult patients in Denmark, 77 pediatric patients in the Netherlands, and 80 patients of all ages in a Dutch hospital that newly implemented CSF CRP testing.
Sixty-six patients were diagnosed with bacterial meningitis. In the hospital implementation cohort, CSF CRP correctly identified all 15 cases, achieving 100% sensitivity and 94% specificity. In pediatric patients, sensitivity was 94% and specificity 98%. Among Danish adult patients, sensitivity and specificity were 85% and 96%, respectively.
“In all [patients with] bacterial meningitis, CRP in CSF was elevated, including 8 patients with a CSF leukocyte count below 1,000 cells/mm3,” said lead study author Sabine E. Olie, of the Department of Neurology at Amsterdam Neuroscience at Amsterdam UMC at the University of Amsterdam, and colleagues. This is important because leukocyte count is often the main tool for diagnosis, but it can be normal in up to 30% of cases.
Combining CSF CRP with leukocyte count further improved diagnostic accuracy. In the implementation cohort, the area under the curve (AUC) for CRP in CSF was 0.99. In comparison, CRP measured in blood had a lower AUC of 0.90.
The test was reliable even when antibiotics were administered prior to lumbar puncture. Nearly 50% of the patients diagnosed with bacterial meningitis had received antibiotics beforehand, but CRP levels in CSF remained elevated.
The researchers noted that CRP in CSF can be easily integrated into hospital laboratories already measuring CRP in blood. Each test costs about €5 (just over $5) and requires no specialized equipment, making it especially promising for resource-limited settings where rapid, accurate diagnostics are needed.
While the study population was limited to European hospitals, the researchers recommended further validation in other geographic and clinical settings. Although CSF lactate wasn't available for all patients, and some samples underwent freeze-thaw cycles, the findings were robust.
The researchers concluded that CRP in CSF could be a practical and cost-effective diagnostic tool, particularly valuable for early detection of bacterial meningitis when used alongside CSF leukocyte counts.
Full author disclosures are available in the original publication.