High-mobility group box 1 protein as a novel biomarker to diagnose healthcare-associated ventriculitis and meningitis: a pilot study.

BACKGROUND The diagnosis of healthcare-associated ventriculitis and meningitis (HAVM) is challenging in the ICU setting. Traditional cerebrospinal fluid (CSF) markers and clinical signs of infection fail to diagnose HAVM in the critically ill setting. We sought to determine the diagnostic accuracy of measuring levels of high-mobility group box 1 (HMGB1) protein in cerebrospinal fluid (CSF) for the diagnosis of HAVM. METHODS In this is a prospective observational cohort study, we enrolled 29 patients with an implanted external ventricular drainage (EVD). We tested the accuracy of CSF-HMGB1 as a diagnostic test for HAVM when compared to standard CSF parameters. RESULTS HAVM was diagnosed in 11/29 (37.9%) patients. These patients had significantly higher CSF-HMGB1 levels compared to patients without HAVM (median [IQR] 43.39 [83.51] ng/mL vs 6.46 ng/mL [10.94]; P<0.001). CSF-HMGB1 and CSF-glucose were independently related to HAVM, with OR's (95% CI) of 15.43 (15.37 to 15.48, P <0.0001) and 0.31 (0.30 to 0.32, P <0.0001), respectively. The AUC [CI] of CSF-HMGB1 to predict HAVM was 0.83 [0.72 to 0.94]. CONCLUSIONS HMGB1 is an accurate marker of HAVM, and it adds incremental diagnostic value when paired with CSF-glucose measurements. Future larger and multicenter studies should assess the incremental diagnostic value of HMGB1 data when used alongside other established CSF markers of infection, and the external validity of these preliminary results.