ArticleThe Journal of clinical investigation2022
High-dose rifampin improves bactericidal activity without increased intracerebral inflammation in animal models of tuberculous meningitis.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 3 of them syntheses that pooled it.
What it found
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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.
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Who cites it
35 citing papers in PubMed, 3 syntheses or guidelines pooled it, 36 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
- Pooled it
- Trial of High-Dose Oral Rifampin in Adults with Tuberculous Meningitis.The New England journal of medicine · 2025Trial
- Intensified Treatment of Tuberculous Meningitis in Adults: A Systematic Review and Meta-analysis.Open forum infectious diseases · 2025Trial
- Ethionamide versus ethambutol-containing first-line regimens for TB meningitis.Antimicrobial agents and chemotherapy · 2026Article
- Addition of Clofazimine Enhances the Activity of Standard Treatment Regimen in a Mouse Model of Tuberculous Meningitis.The Journal of infectious diseases · 2026Article
- Beyond Rifampin: Evaluating Rifapentine and Rifabutin as Alternative Treatments for Tuberculous Meningitis.The Journal of infectious diseases · 2026Article
- Host-directed treatments for tuberculous meningitis utilizing a multi-platform approach across mouse and human models.Nature communications · 2026Article
- Anti-tuberculosis drug treatment and adverse reactions in 546 children with tuberculosis in Chongqing, China: A 10-year retrospective study.The Journal of international medical research · 2026Article
- Radiolabeled Antimicrobials for Infection Imaging: A Scoping Review.International journal of molecular sciences · 2026Article
- Host-directed treatments for tuberculous meningitis: A multi-platform approach across mouse and human models.Research square · 2026Article
- Host-directed nanotherapy for the treatment and imaging of tuberculous meningitis.Theranostics · 2026Article
- Cerebrospinal fluid penetration of cycloserine/terizidone and clofazimine in patients with pulmonary TB.Antimicrobial agents and chemotherapy · 2025Article
- Tuberculous meningitis alters the proteomic landscape of brain-derived extracellular vesicles.bioRxiv : the preprint server for biology · 2025Article
- MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.Journal of neuroinflammation · 2025Article
- Improved Radiosynthesis of [ACS infectious diseases · 2025Article
- Spatially heterogeneous lipid dysregulation in tuberculous meningitis.Neurobiology of disease · 2024Article
- Proapoptotic Bcl-2 inhibitor as host directed therapy for pulmonary tuberculosis.Research square · 2024Article
- Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs.Nature communications · 2024Observational
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Tuberculous meningitis (TB meningitis) is the most severe form of tuberculosis (TB), requiring 12 months of multidrug treatment for cure, and is associated with high morbidity and mortality. High-dose rifampin (35 mg/kg/d) is safe and improves the bactericidal activity of the standard-dose (10 mg/kg/d) rifampin-containing TB regimen in pulmonary TB. However, there are conflicting clinical data regarding its benefit for TB meningitis, where outcomes may also be associated with intracerebral inflammation. We conducted cross-species studies in mice and rabbits, demonstrating that an intensified high-dose rifampin-containing regimen has significantly improved bactericidal activity for TB meningitis over the first-line, standard-dose rifampin regimen, without an increase in intracerebral inflammation. Positron emission tomography in live animals demonstrated spatially compartmentalized, lesion-specific pathology, with postmortem analyses showing discordant brain tissue and cerebrospinal fluid rifampin levels and inflammatory markers. Longitudinal multimodal imaging in the same cohort of animals during TB treatment as well as imaging studies in two cohorts of TB patients demonstrated that spatiotemporal changes in localized blood-brain barrier disruption in TB meningitis are an important driver of rifampin brain exposure. These data provide unique insights into the mechanisms underlying high-dose rifampin in TB meningitis with important implications for developing new antibiotic treatments for infections.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.