A Clinical Practice Guideline for Tuberculous Meningitis

International TBM guideline group · 2025 · international

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Authors: Joseph Donovan, Fiona V Cresswell, Elizabeth W Tucker et al.
Title: A Clinical Practice Guideline for Tuberculous Meningitis
Journal: The Lancet. Infectious diseases, 2025
DOI: 10.1016/S1473-3099(25)00364-0
Licence: CC BY 4.0
Changes: Verbatim excerpts; formatting adapted

Full text retrieved 2026-10-27 from Europe PMC · PMC12419961

Licence statement of the original publication

This work is licensed under a BY 4.0 International license.

This page reproduces excerpts of the original publication; the original is authoritative. It has not been reviewed by a physician, does not state a recommendation of Medelix and does not replace medical advice. The guideline may have been updated since.

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Recommendations

Verbatim, with grade of recommendation or strength of consensus where given.

Questions

1. How accurate are CSF microscopy and biochemistry to diagnose TBM?
Population: All individuals in hospital being evaluated for TBM
Intervention: CSF cell microscopy, biochemistry, lactate
Comparators: a) Definite or probable TBM, and b) Positive CSF mycobacterial culture
Outcome: True positive (TP), false positive (FP), true negative (TN) and false negative (FN)
Conclusion: Insufficient evidence to recommend for or against use
2. How accurate are microbiological and molecular tests to diagnose TBM?
Intervention: Each of ZN smear microscopy, Xpert, Xpert Ultra, Mycobacterial culture (MGIT, LJ, or MODS assay), Alere-LAM
3. How accurate is adenosine deaminase to diagnose TBM?
Intervention: Adenosine deaminase (ADA)
Conclusion: Very low certainty of evidence for test accuracy, weak recommendation for use in the diagnosis of TBM
4. How accurate is neuroimaging to diagnose TBM?
Population: All individuals in hospital being evaluated for TBM or other CNS TB (e.g., spinal TB and tuberculomas)
Intervention: CT or MRI brain (+/- contrast)
Conclusion: Insufficient evidence to recommend for or against use in diagnosis*
*Insufficient evidence to recommend for or against neuroimaging use as a diagnostic tool for TBM. However, neuroimaging may demonstrate features that increase the likelihood of a diagnosis of TBM, and neuroimaging has an important role in evaluating for intracerebral mass lesions and ensuring lumbar puncture safety (see Figure 1). Baseline neuroimaging is recommended.
Definitions: CSF=cerebrospinal fluid. CT=computed tomography. LJ=Lowenstein-Jensen. MGIT=Mycobacteria Growth Indicator Tube. MODS=Microscopic Observation Drug Susceptibility. MRI=Magnetic resonance imaging. TBM-tuberculous meningitis
1. Should active management (medical and/or surgical) or standard of care be used in individuals with TBM and hydrocephalus/raised ICP?
Population: Adults or children (with or without HIV) in hospital with TBM, and hydrocephalus/raised ICP
Intervention: Active medical (repeated lumbar punctures with diuretics) or surgical management (or a combination)
Comparators: Standard WHO therapya
Outcome: Mortality, and morbidity, radiological outcome, complications (including treatment failure)
Conclusion: Insufficient evidence to make a recommendation, for or against active medical or surgical management of hydrocephalus/raised ICP
2. Should a VPS or ETV be used for the surgical management of hydrocephalus in patients with TBM?
Intervention: Surgical management of hydrocephalus by VPS
Comparators: Surgical management of hydrocephalus by ETV
Outcome: Mortality, morbidity, radiological outcome, complications (including treatment failure)
Conclusion: Insufficient evidence to recommend VPS over ETV if surgical intervention is required. Discretion of the treating clinician is required
3. Should surgical management of tuberculomas with or without TBM occur at time of diagnosis or after medical treatment failure?
Population: Adults or children (with or without HIV) in hospital with tuberculomas (with or without TBM)
Intervention: Surgical management of tuberculomas at diagnosis
Comparators: Surgical management after failure of standard WHO therapies
Conclusion: Insufficient evidence to make a recommendation for or against surgical management of tuberculomas at diagnosis or after medical treatment failure
4. Should surgical management of TB abscesses with or without TBM occur at time of diagnosis or after medical treatment failure?
Population: Adults or children (with or without HIV) in hospital with TB abscesses (with or without TBM)
Intervention: Surgical management of TB abscesses at diagnosis
Conclusion: Insufficient evidence to make a recommendation for or against surgical management of TB abscesses at diagnosis or after medical treatment failure
5. Should the management of hyponatremia in patients with TBM be based on aetiology?
Population: Adults or children (with or without HIV) in hospital with TBM and hyponatraemia
Intervention: Treatment of hyponatremia tailored by aetiology (CSW/SIADH)
Comparators: Treatment of hyponatremia not tailored by aetiology (CSW/SIADH)
Outcome: Mortality, morbidity, complications (including treatment failure)
Conclusion: Insufficient evidence to make a recommendation for or against treatment of hyponatremia tailored by aetiology
6. Should all patients with TBM be assessed for clinical and sub-clinical seizures?
Population: Adults or children (with or without HIV) in hospital with TBM
Intervention: Assessed for clinical and sub-clinical seizures by EEG
Comparators: Not assessed for clinical and sub-clinical seizures by EEG
Outcome: Mortality and morbidity
Conclusion: Insufficient evidence to make a recommendation for or against assessment for clinical and sub-clinical seizures

Rationale and context for recommendations

1How accurate are cerebrospinal fluid (CSF) microscopy and biochemistry to diagnose TBM?
2How accurate are microbiological and molecular tests to diagnose TBM?
3How accurate is adenosine deaminase (ADA) to diagnose TBM?
4How accurate is neuroimaging to diagnose TBM?

CSF volume

We recommend sampling ≥6mLs CSF for dedicated M. tuberculosis testing.(25) Larger CSF volumes are a strong predictor of positive ZN stain, M. tuberculosis culture, and Xpert.(26,31) CSF should be centrifuged at 3000g for 20 minutes, with the cell pellet subject to mycobacterial tests.(25,31,32)

Anti-TB chemotherapy

1a. Does increasing the rifampicin dose reduce mortality in adults with TBM vs. standard 10mg/kg/day dosing?
Population: Adults in hospital requiring treatment for TBM
Intervention: Rifampicin dosing of >10mg/kg/day, given orally or parenterally
Comparators: Rifampicin dosing of 10mg/kg/day, given orally or parenterally
Conclusion: Moderate quality of evidence, does not support increased dosing of rifampicin at 15mg/kg/day and above*
1b. Does rifampicin dosing >20mg/kg/day reduce mortality in adults with TBM vs. standard 10mg/kg/day dosing?
Intervention: Rifampicin dosing of >20 mg/kg/day, given orally or parenterally
Conclusion: Insufficient evidence to recommend for or against rifampicin dosing of >20mg/kg/day*
*Trial results from HARVEST (ISRCTN15668391, reporting in 2025) and INTENSE-TBM (NCT04145258, reporting in 2026) are likely to provide definitive data to address PICO questions 1a and 1b.
2a. Does adjunctive fluoroquinolone therapy reduce mortality in adults from TBM vs. no fluoroquinolone?
Intervention: Adjunctive fluoroquinolone
Comparators: Standard anti-TB chemotherapy
Conclusions: High quality of evidence. In adults with fully drug-susceptible M. tuberculosis, strong recommendation against adding a fluoroquinolone to the TB regimen or using a fluoroquinolone in place of another drug in the regimen.
For individuals with a high probability of TBM caused by isoniazid-resistant bacteria, strong recommendation for adding a fluoroquinolone to the regimen or using a fluoroquinolone in place of isoniazid in the regimen
2b. Does adjunctive linezolid reduce mortality in adults from TBM vs. no linezolid?
Intervention: Adjunctive linezolid
Conclusion: Insufficient evidence to make recommendation, for or against use of linezolid
3. Does higher dosing, or alternative administration routes, of other TB drugs reduce mortality in adults from TBM?
Intervention: Change in dose, route of administration or addition/substitution, of any other TB drugs
Conclusion: Insufficient evidence to make recommendation, for or against higher dosing or alternative administration routes, or other TB drugs
4. Is treatment duration less than 12 months effective in TBM in adults?
Intervention: Anti-TB chemotherapy duration of less than 12 months
Comparators: Standard anti-TB chemotherapy duration of 12 months
Conclusion: Insufficient evidence to make a recommendation, for or against less than 12 months anti-TB chemotherapy
5. What is the optimal treatment for childhood TBM?
Population: Children in hospital requiring treatment for TBM
Intervention: 6 months high-dose isoniazid, high-dose rifampicin, pyrazinamide and ethionamide (6HRZEto)
Conclusion: Insufficient evidence to make a recommendation for or against the shorter regimen. Either the 6-month (6H15-20 R22.5-30Z35-45Eto17.5-22.5) intensive regimen or the standard 12-month regimen can be used.
Standard antibiotic dosing achieves subtherapeutic levels in children; please see narrative under Anti-TB chemotherapy, section 5.

Rationale and context for recommendations

1Does increasing the rifampicin dosing reduce mortality in adults with TBM vs. standard 10mg/kg/day dosing?
2Does an adjunctive fluoroquinolone or linezolid reduce mortality in adults from TBM?
3Does higher dosing, or alternative administration routes, of other TB drugs reduce mortality in adults from TBM?
4Is treatment duration less than 12 months effective in TBM in adults?
5What is the optimal treatment for childhood TBM?

Adjunctive therapy

1. Should corticosteroids be used as an adjunctive therapy in patients with TBM?
Population: Adults and children with TBM
Intervention: Anti-TB chemotherapy with adjunctive corticosteroids
Comparators: Anti-TB chemotherapy without adjunctive corticosteroids
Conclusions: High certainty of evidence, strong recommendation for use in individuals without HIV.
High certainty of evidence, weak recommendation for use in PLWH, therefore decision to use should be made on a case-by-case basis
2. What is the optimal timing of antiretroviral therapy in CNS TB?
Intervention: Immediate ART (within 7 days of commencing anti-TB treatment)
Comparators: Deferred ART initiation (after 2 months of anti-TB treatment)
Conclusion: High certainty of evidence, weak recommendation to defer ART initiation 4-8 weeks after starting anti-TB treatment
3. What other adjunctive therapies can be considered for the management of TBM?
Intervention: Adjunctive aspirin, thalidomide, infliximab, cyclophosphamide, anakinra, or interferon-gamma
Comparators: Anti-TB chemotherapy without above listed adjunctive agents
Conclusion: Insufficient evidence to make a recommendation, for or against adjunctive aspirin, thalidomide, infliximab, cyclophosphamide, anakinra, or interferon-gamma. Decision to initiate these treatments should be made on a case-by-case basis based on factors discussed in the guideline
Definitions: ART=antiretroviral therapy. CNS=central nervous system

Rationale and context for recommendations

1Should corticosteroids be used as an adjunctive therapy in patients with TBM?
2What is the optimal timing of antiretroviral therapy in CNS TB?
3What other adjunctive therapies can be considered for the management of TBM?
1Should active management (medical and/or surgical) or standard of care be used in individuals with TBM and hydrocephalus/raised ICP?
2Should a VPS or ETV be used for the surgical management of hydrocephalus in patients with TBM?
3Should surgical management of tuberculomas with or without TBM occur at time of diagnosis or after medical treatment failure? 4. Should surgical management of TB abscesses with or without TBM occur at time of diagnosis or after medical treatment failure?
5Should the management of hyponatremia in patients with TBM be based on aetiology?
6Should all patients with TBM be assessed for clinical and sub-clinical seizures?

Abstract

Tuberculous meningitis (TBM) is the most severe form of tuberculosis, causing death or disability in around half of those affected. There are no up-to-date international guidelines defining its optimal management. Therefore, the Tuberculous Meningitis International Research Consortium conducted a systematic review of available evidence to address key management questions and develop practice guidance. The consortium includes representatives from India, Indonesia, South Africa, Uganda, Vietnam, Australia, Netherlands, United Kingdom, and United States. Questions were developed using the PICO (Population, Intervention, Comparator, Outcome) format for TBM diagnosis, anti-tuberculosis chemotherapy, adjunctive anti-inflammatory therapy, and neurocritical/neurosurgical care. A GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach was used to assess certainty (quality) of evidence and determine the direction and strength of recommendations for each PICO question. We provide evidence-based recommendations for the optimal treatment and diagnosis of TBM, alongside expert opinion. We expose substantial knowledge and evidence gaps, thereby highlighting current research priorities.

Contents of the original publication

The section headings of the original.

Introduction
Rationale for the guideline
Guideline scope
Target audience
Methods
Guideline inception
Questions
Search strategy and selection criteria
Study selection
Certainty of evidence
Limitations
Good practice points
Recommendations
Diagnosis of TBM
Anti-TB chemotherapy
Adjunctive therapy
Good practice points
Neurocritical and neurosurgical care

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