ORIGINAL ARTICLE   Free access

Minerva Anestesiologica 2021 January;87(1):43-51

DOI: 10.23736/S0375-9393.20.14222-6

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

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

Simone PIVA ^{1, 2} ✉, Filippo ALBANI ², Nazzareno FAGONI ², Eugenio MONTI ³, Liana SIGNORINI ⁴, Fabio TURLA ², Frank A. RASULO ^{1, 2}, Marco FONTANELLA ⁵, Nicola LATRONICO ^{1, 2}

¹ Department of Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy; ² Department of Anesthesiology, Critical Care and Emergency, Spedali Civili University Hospital, Brescia, Italy; ³ Unit of Biochemistry, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy; ⁴ Second Division of Clinical Infectious Diseases, Department of Infectious Diseases, Spedali Civili University Hospital, Brescia, Italy; ⁵ Division of Neurosurgery, Department of Neuroscience, Spedali Civili University Hospital, Brescia, Italy

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 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.

KEY WORDS: HMGB1 protein; Meningitis; Biomarkers