Heparin-binding protein: A diagnostic marker of acute bacterial meningitis*

Background: The early detection of bacterial meningitis is crucial for successful outcome. Heparin-binding protein, a potent inducer of increased vascular permeability, is released from activated neutrophils in severe sepsis. Objective: In this study we investigated whether heparin-binding protein levels in cerebrospinal fluid could be used as a diagnostic marker for acute bacterial meningitis. Design: One prospective and one retrospective patient cohort from two university hospitals in Sweden were analyzed. Setting and Patients: Cerebrospinal fluid samples were collected from 174 patients with suspected central nervous system infection. Thirty-seven patients with acute community-acquired bacterial meningitis, four patients with neurosurgical bacterial meningitis, 29 patients with viral meningitis or encephalitis, seven patients with neuroborreliosis, and 97 control patients were included. Interventions: None. Measurements and Main Results: Cerebrospinal fluid samples were analyzed for the concentrations of heparin-binding protein, lactate, protein, glucose, neutrophils, and mononuclear cells. Heparin-binding protein levels were significantly higher (p < .01) in patients with acute bacterial meningitis (median 376 ng/mL, range 12–858 ng/mL) than in patients with viral central nervous system infection (median 4.7 ng/mL, range 3.0–41 ng/mL) or neuroborreliosis (median 3.6 ng/mL, range 3.2–10 ng/mL) or in control patients with a normal cerebrospinal fluid cell count (median 3.5 ng/mL, range 2.4–8.7 ng/mL). In the prospectively studied group, a heparin-binding protein concentration exceeding 20 ng/mL gave a sensitivity of 100%, a specificity of 99.2%, and positive and negative predictive values of 96.2% and 100%, respectively, in diagnosing acute bacterial meningitis. The area under the receiver-operating characteristic curve for heparin-binding protein was 0.994, which was higher than for the other investigated parameters. Conclusion: Elevated cerebrospinal fluid levels of heparin-binding protein distinguish between patients with acute bacterial meningitis and patients with other central nervous system infections.