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Updated: Jun 21, 2026

Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid for the Detection of Central Nervous System Pathogens
Published on: April 17, 2026
Following the lactate trail: sequential CSF lactate trend analysis in diagnosing post-neurosurgical meningitis - a
Vidhya T1, Srinivasa Sundara Rajan R, Rosemary Shaji V1
1Department of Neuromicrobiology, National Institute of Mental Health and Neurosciences, Bengaluru, India.
Objectives:
Post-neurosurgical bacterial meningitis (PNBM) is one of the major complications that causes high mortality in an era of antimicrobial resistance. Differentiating infective meningitis from aseptic meningitis remains challenging when we rely on culture, as it has lower sensitivity, and conventional cerebrospinal fluid biomarkers cannot differentiate between the two.
Methods:
This study aimed to evaluate the diagnostic utility of sequential cerebrospinal fluid lactate as a biomarker in patients with PNBM, to establish the optimal cutoff. This retrospective study included 49 PNBM and 27 non-PNBM patients from January to December 2024. In each category, a minimum of 3 and a maximum of 5 samples were considered for sequential CSF lactate analysis. In the PNBM group, ROC curve analysis revealed that CSF lactate levels had the highest diagnostic accuracy (AUC of 0.89, Youden's index, 0.78), followed by cell count (AUC of 0.86), glucose (AUC of 0.79), and protein (AUC of 0.49).
Results:
Sequential CSF lactate analysis showed a significant difference between the PNBM and non-PNBM groups (p < 0.001). The optimal CSF lactate cutoff was 4.7 mmol/L, with 90% and 89% sensitivity and specificity, respectively. Among non-survivors, the average CSF lactate was 6.1 mmol/L compared to that of survivors.
Discussion:
Our study shows that rather than relying on a single value, sequential CSF lactate monitoring helps to identify meningitis cases earlier than other CSF biomarkers and when culture results remain negative. A CSF lactate of 4.7 mmol/L serves as a diagnostic marker for PNBM, with >6.1 mmol/L being associated with higher mortality.
Insights
Sequential cerebrospinal fluid lactate monitoring effectively diagnoses post-neurosurgical bacterial meningitis (PNBM) earlier than other biomarkers. A lactate level of 4.7 mmol/L is optimal for diagnosis, with higher levels indicating increased mortality risk.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biomarker Discovery
Background:
- Post-neurosurgical bacterial meningitis (PNBM) presents a significant mortality risk, exacerbated by antimicrobial resistance.
- Accurate differentiation between infective and aseptic meningitis is challenging due to the limitations of conventional cerebrospinal fluid (CSF) biomarkers and culture sensitivity.
Purpose of the Study:
- To evaluate the diagnostic utility of sequential CSF lactate levels in identifying PNBM.
- To establish an optimal cutoff value for CSF lactate as a diagnostic marker for PNBM.
Main Methods:
- A retrospective study involving 49 PNBM and 27 non-PNBM patients.
- Sequential CSF lactate analysis was performed on 3-5 samples per patient.
- Receiver Operating Characteristic (ROC) curve analysis was used to determine diagnostic accuracy.
Main Results:
- Sequential CSF lactate analysis demonstrated a significant difference between PNBM and non-PNBM groups (p < 0.001).
- CSF lactate achieved the highest diagnostic accuracy (AUC=0.89), outperforming cell count, glucose, and protein levels.
- An optimal CSF lactate cutoff of 4.7 mmol/L was identified, with 90% sensitivity and 89% specificity.
Conclusions:
- Sequential CSF lactate monitoring offers earlier and more accurate diagnosis of PNBM compared to traditional biomarkers, especially when cultures are negative.
- A CSF lactate cutoff of 4.7 mmol/L is a reliable diagnostic marker for PNBM.
- CSF lactate levels exceeding 6.1 mmol/L are associated with increased mortality in PNBM patients.

