SynthesisClinical infectious diseases : an official publication of the Infectious Diseases Society of America2020
Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.
Synthesis in Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
44 citing papers in PubMed, 5 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- High dose of rifampicin in the treatment of tuberculous meningitis: a systematic review and meta-analysis of randomized controlled trials.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026Pooled it
- A clinical practice guideline for tuberculous meningitis.The Lancet. Infectious diseases · 2026Guideline
- Efficacy & safety of high-dose rifampicin in pulmonary tuberculosis: A systematic review & meta-analysis.The Indian journal of medical research · 2025Pooled it
- Applications of Model-Based Meta-Analysis in Drug Development.Pharmaceutical research · 2022Pooled it
- Intensified Antituberculosis Therapy Regimen Containing Higher Dose Rifampin for Tuberculous Meningitis: A Systematic Review and Meta-Analysis.Frontiers in medicine · 2022Pooled it
- Immediate or high-dose antituberculosis therapy for HIV-related sepsis in Tanzania and Uganda (ATLAS): a phase 3, open-label, randomised, controlled, 2 × 2 factorial, superiority trial.The Lancet. Infectious diseases · 2026Trial
- Population Pharmacokinetic Modeling of Standard- and High-Dose Rifampicin for Tuberculosis Preventive Therapy in the 2R2 Randomized Controlled Trial.The Journal of infectious diseases · 2026Trial
- Trial of High-Dose Oral Rifampin in Adults with Tuberculous Meningitis.The New England journal of medicine · 2025Trial
- Population Pharmacokinetics of Rifampicin in Plasma and Cerebrospinal Fluid in Adults With Tuberculosis Meningitis.The Journal of infectious diseases · 2025Trial
- Linezolid Population Pharmacokinetic Model in Plasma and Cerebrospinal Fluid Among Patients With Tuberculosis Meningitis.The Journal of infectious diseases · 2024Trial
- Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2022Trial
- Plasma Pharmacokinetics of High-Dose Oral versus Intravenous Rifampicin in Patients with Tuberculous Meningitis: a Randomized Controlled Trial.Antimicrobial agents and chemotherapy · 2021Trial
- Fixed Dose Combinations as an Advantage for the Treatment of Pediatric Tuberculosis: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Drug repurposing for disease-modifying effects in multiple system atrophy.Translational neurodegeneration · 2026Review
- Examining the Reliability of Model-Based Meta-Analysis (MBMA) Outcomes: A Simulation Study.CPT: pharmacometrics & systems pharmacology · 2026Article
- Pre-treatment untargeted cerebrospinal fluid metabolomic profiling in tuberculous meningitis uncovers pathways associated with mortality.Med (New York, N.Y.) · 2025Article
- The importance of getting the dose right in the treatment of tuberculosis.Breathe (Sheffield, England) · 2025Article
- Inflammatory markers in the cerebrospinal fluid linked to mortality in tuberculous meningitis.Brain communications · 2025Article
- Recent advances in immunopathogenesis and clinical practice: mastering the challenge-managing of non-tuberculous mycobacteria.Frontiers in immunology · 2025Review
- Rifabutin central nervous system concentrations in a rabbit model of tuberculous meningitis.Antimicrobial agents and chemotherapy · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntensified antimicrobial treatment with higher rifampicin doses may improve outcome of tuberculous meningitis, but the desirable exposure and necessary dose are unknown. Our objective was to characterize the relationship between rifampicin exposures and mortality in order to identify optimal dosing for tuberculous meningitis.
methodsAn individual patient meta-analysis was performed on data from 3 Indonesian randomized controlled phase 2 trials comparing oral rifampicin 450 mg (~10 mg/kg) to intensified regimens including 750-1350 mg orally, or a 600-mg intravenous infusion. Pharmacokinetic data from plasma and cerebrospinal fluid (CSF) were analyzed with nonlinear mixed-effects modeling. Six-month survival was described with parametric time-to-event models.
resultsPharmacokinetic analyses included 133 individuals (1150 concentration measurements, 170 from CSF). The final model featured 2 disposition compartments, saturable clearance, and autoinduction. Rifampicin CSF concentrations were described by a partition coefficient (5.5%; 95% confidence interval [CI], 4.5%-6.4%) and half-life for distribution plasma to CSF (2.1 hours; 95% CI, 1.3-2.9 hours). Higher CSF protein concentration increased the partition coefficient. Survival of 148 individuals (58 died, 15 dropouts) was well described by an exponentially declining hazard, with lower age, higher baseline Glasgow Coma Scale score, and higher individual rifampicin plasma exposure reducing the hazard. Simulations predicted an increase in 6-month survival from approximately 50% to approximately 70% upon increasing the oral rifampicin dose from 10 to 30 mg/kg, and predicted that even higher doses would further improve survival.
conclusionsHigher rifampicin exposure substantially decreased the risk of death, and the maximal effect was not reached within the studied range. We suggest a rifampicin dose of at least 30 mg/kg to be investigated in phase 3 clinical trials.
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