Predictors of infectious meningitis or encephalitis: the yield of cerebrospinal fluid in a cross-sectional study

Abstract

Background: Cerebrospinal fluid (CSF) analyses are recommended in patients with meningitis and/or encephalitis, but evidence regarding its diagnostic yield is low. We aimed to determine predictors of infectious pathogens in the CSF of adult patients presenting with meningitis, and/or encephalitis.

Methods: Consecutive patients with meningitis and/or encephalitis form 2011-17 at a Swiss academic medical care center were included in this cross-sectional study. Clinical, neuroradiologic, and laboratory data were collected as exposure variables. Infectious meningitis and/or encephalitis were defined as the composite outcome. For diagnosis of bacterial meningitis the recommendations of the European Society of Clinical Microbiology and Infectious Diseases were followed. Viral meningitis was diagnosed by detection of viral ribonucleic or deoxyribonucleic acid in the CSF. Infectious encephalitis was defined according to the International Encephalitis Consortium (IEC). Meningoencephalitis was diagnosed if the criteria for meningitis and encephalitis were fulfilled. Multinomial logistic regression was performed to identify predictors of the composite outcome. To quantify discriminative power, the c statistic analogous the area under the receiver-operating curve (AUROC) was calculated. An AUROC between 0.7-0.8 was defined as "good", 08-0.9 as "excellent", and > 0.9 as "outstanding". Calibration was defined as "good" if the goodness of fit tests revealed insignificant p-values.

Results: Among 372 patients, infections were diagnosed in 42.7% presenting as meningitis (51%), encephalitis (32%), and meningoencephalitis (17%). Most frequent infectious pathogens were Streptococcus pneumoniae, Varicella zoster, and Herpes simplex 1&2. While in multivariable analysis lactate concentrations and decreased glucose ratios were the only independent predictors of bacterial infection (AUROCs 0.780, 0.870, and 0.834 respectively), increased CSF mononuclear cells were the only predictors of viral infections (AUROC 0.669). All predictors revealed good calibration.

Conclusions: Prior to microbiologic workup, CSF data may guide clinicians when infection is suspected while other laboratory and neuroradiologic characteristics seem less useful. While increased CSF lactate and decreased glucose ratio are is the most reliable predictors of bacterial infections in patients with meningitis and/or encephalitis, only mononuclear cell counts predicted viral infections.

Trial registration: ClinicalTrials.gov identifier NCT03856528. Registered on February 26th 2019.

Keywords: Cerebrospinal fluid; Encephalitis; Meningitis; Meningoencephalitis; Neurocritical care.

Conflict of interest statement

None of the authors report conflicts of interests relevant to this study.

Tolga Dittrich received a personal grant from the Scientific Society Basel.

Stephan Marsch reports no disclosures.

Adrian Egli reports no disclosures.

Stephan Rüegg received unconditional research grants from UCB and CSL Behring. He received honoraria from serving on the scientific advisory boards of Desitin, Eisai, GlaxoSmithKline, Pfizer and UCB, travel grants from Desitin, speaker fees from UCB and Novartis, compensations from serving as a consultant for Novartis, Sandoz and UCB. He is co-PI of the Swiss National Found Grant #320030_169379 / 1. He serves as president on the board of the Swiss League against Epilepsy and is on the editorial board of EPILETOLOGIE and the SWISS EEG BULLETIN. He does not hold any stocks of any pharmaceutical companies or manufacturers of medical devices.

Gian Marco De Marchis was or is supported by the Swiss National Science Foundation; Science Funds [Wissenschaftsfonds] of the University Hospital Basel and University of Basel; Bangerter-Rhyner-Stiftung; Swisslife Jubiläumsstiftung for Medical Research; Swiss Neurological Society; Fondazione Dr. Ettore Balli; De Quervain research grant; Thermo Fisher GmbH. He received travel and advisory board honoraria by Bayer and speaker honoraria by Medtronic and BMS/Pfizer.

Sarah Tschudin-Sutter is a member of the Astellas and MSD Advisory Boards for C. difficile, of the Pfizer Antiinfectives Advisory Board for and reports grants from the Swiss National Science Foundation NRP72 (407240_167060), the Bangerter-Rhyner Stiftung, the Fonds zur Förderung von Lehre und Forschung der Freiwilligen Akademischen Gesellschaft Basel, and the Jubiläumsstiftung from Swiss Life.

Raoul Sutter received research grants from the Swiss National Foundation (No 320030_169379), the Research Fund of the University Basel, the Scientific Society Basel, and the Bangerter-Rhyner Foundation. He received personal grants from UCB-pharma and holds stocks from Novartis, Roche and Johnson & Johnson.

Figures

Fig. 1

Flow chart. CSF = cerebrospinal fluid. 26.3% (n = 56) alternative CNS pathologies: 10 autoimmune/paraneoplastic encephalitides; 7 strokes; 3 intracranial hemorrhages; 3 traumatic brain injuries; 3 septic encephalopathies; 3 brain tumors; 3 prion diseases; 11 others

Fig. 2

Receiver operating characteristic analyses for the prediction of meningitis and/or encephalitis with identified infectious pathogens by CSF parameters (excluding protozoal infections). CSF = cerebrospinal fluid