Evidence brief: Early mortality risk stratification in childhood bacterial meningitis using cerebrospinal fluid glucose and protein levels and their combinations: A multicontinental cohort study

Abstract

Bacterial meningitis remains a major cause of death and neurological disability in children worldwide, particularly in low-resource settings where access to intensive care is limited. Cerebrospinal fluid (CSF) glucose, protein, and leukocyte concentrations are routinely measured at hospital presentation, yet their potential for early risk stratification – individually or in combination – has not been clearly defined. Because mortality risk is often difficult to assess at admission, identifying simple CSF-based thresholds that help clinicians recognize high-risk patients could improve triage and management globally.

We evaluated CSF glucose, protein and leukocyte levels in 1598 children with bacteriologically confirmed bacterial meningitis across six countries in Latin America, Angola, and Finland to determine their individual and combined associations with mortality and neurological outcome. CSF glucose, protein, and leukocyte counts were measured at admission and examined in relation to in-hospital mortality and neurological outcome at discharge, as assessed by the Glasgow Outcome Scale. CSF glucose and protein concentrations were categorized into five clinically interpretable groups. Mortality increased progressively with decreasing CSF glucose (from 8% to 29%) and with increasing protein concentrations (from 5% to 23%). Children with both low CSF glucose (<10 mg/dL) and high CSF protein (≥200 mg/dL) had a mortality rate of 27% compared with 1% among those with normal CSF glucose and protein. A CSF leukocyte count <500/µL was also associated with increased mortality. Lower CSF glucose (ρ = 0.24; P < .001) and higher protein (ρ = 0.15; P < .001) were both associated with poorer neurological outcomes.

Routine CSF markers available at the time of hospital admission provide prognostic information that supports risk stratification in pediatric bacterial meningitis. Simple CSF-based thresholds—particularly when CSF glucose and protein are interpreted in combination—may help identify high-risk children early and guide clinical prioritization in settings with limited critical care capacity.

Introduction

Bacterial meningitis remains a severe and life-threatening disease in children, with substantial mortality and neurological sequelae despite global vaccination programs and advances in antimicrobial therapy [1,2]. The burden is greatest in low- and middle-income countries, where delays in diagnosis and limited access to intensive care contribute to high case fatality rates. Early risk assessment is crucial for guiding management and resource allocation, yet the prognostic information embedded in routine cerebrospinal fluid (CSF) measurements – particularly glucose and protein – has not been fully utilized in clinical practice. Clinical presentation of bacterial meningitis is variable: although the classical triad of fever, headache, and vomiting is well recognized, many children present with nonspecific findings, making early diagnosis challenging [3–6]. Consequently, lumbar puncture remains essential for early evaluation in all suspected cases.

Because the causative pathogen is seldom identified at admission except by Gram stain, clinicians rely on routine CSF analyses to guide diagnosis and early treatment decisions. In bacterial meningitis, CSF glucose is typically reduced, protein is elevated, and leukocyte counts are increased, reflecting inflammatory processes within the central nervous system [7,8]. However, laboratory findings vary widely between patients. Approximately 6% of children with culture-confirmed bacterial meningitis have normal CSF leukocyte counts, and lymphocyte predominance is observed in up to 10% of cases [9]. Such variability limits the diagnostic and prognostic value of CSF leukocyte counts alone.