ArticleClinical pharmacology and therapeutics2015
Pediatric tuberculous meningitis: Model-based approach to determining optimal doses of the anti-tuberculosis drugs rifampin and levofloxacin for children.
Article in Clinical pharmacology and therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03827811 (Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis), which is not on this map. Cited by 36 papers, 2 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.
Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis
Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
- Efficacy & safety of high-dose rifampicin in pulmonary tuberculosis: A systematic review & meta-analysis.The Indian journal of medical research · 2025Pooled it
- Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Pooled it
- Population Pharmacokinetics of Rifampicin in Plasma and Cerebrospinal Fluid in Adults With Tuberculosis Meningitis.The Journal of infectious diseases · 2025Trial
- 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
- Pretomanid dose selection for pulmonary tuberculosis: An application of multi-objective optimization to dosage regimen design.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Challenges in conducting trials for pediatric tuberculous meningitis: lessons from the field.The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease · 2019Trial
- Pharmacokinetics of Second-Line Antituberculosis Drugs in Children with Multidrug-Resistant Tuberculosis in India.Antimicrobial agents and chemotherapy · 2018Trial
- Population pharmacokinetics and exposure-response analysis of levofloxacin in Chinese pediatric patients with severe refractoryAntimicrobial agents and chemotherapy · 2026Article
- An unusual presentation of miliary tuberculosis with medullary nephrocalcinosis in an infant.Radiology case reports · 2026Article
- Basal Ganglia Ischemic Stroke as Sentinel Sign for Pediatric Tuberculous Meningitis in an Immunocompetent Child: A Case Report.Pediatric reports · 2026Article
- Deriving Dosages for Levofloxacin Tuberculosis Preventive Treatment for Young People Exposed to Rifampicin-Resistant Tuberculosis.The Journal of infectious diseases · 2025Article
- Article
- Parametric Population Pharmacokinetics Model Repository of Rifampicin: Model-Informed Individualized Therapy.Clinical pharmacology : advances and applications · 2025Article
- Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies.Pharmaceutics · 2024Review
- Angiopep-2 Modified Exosomes Load Rifampicin with Potential for Treating Central Nervous System Tuberculosis.International journal of nanomedicine · 2023Article
- [Tuberculosis-Update 2022].Monatsschrift Kinderheilkunde : Organ der Deutschen Gesellschaft fur Kinderheilkunde · 2023Article
- Childhood Tuberculosis: Historical Perspectives, Recent Advances, and a Call to Action.Journal of the Pediatric Infectious Diseases Society · 2022Article
- Tuberculosis in Children.Infectious disease clinics of North America · 2022Review
- Risk factors for ischemic stroke in children with tuberculous meningitis.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
Corrections and comments
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Authors and funding
13 authors at 9 institutions in 5 countries.
Funding
Abstract
Pediatric tuberculous meningitis (TBM) is a highly morbid, often fatal disease. Standard treatment includes isoniazid, rifampin, pyrazinamide, and ethambutol. Current rifampin dosing achieves low cerebrospinal fluid (CSF) concentrations, and CSF penetration of ethambutol is poor. In adult trials, higher-dose rifampin and/or a fluoroquinolone reduced mortality and disability. To estimate optimal dosing of rifampin and levofloxacin for children, we compiled plasma and CSF pharmacokinetic (PK) and outcomes data from adult TBM trials plus plasma PK data from children. A population PK/pharmacodynamic (PD) model using adult data defined rifampin target exposures (plasma area under the curve (AUC)0-24 = 92 mg*h/L). Levofloxacin targets and rifampin pediatric drug disposition information were literature-derived. To attain target rifampin exposures, children require daily doses of at least 30 mg/kg orally or 15 mg/kg intravenously (i.v.). From our pediatric population PK model, oral levofloxacin doses needed to attain exposure targets were 19-33 mg/kg. Our results provide data-driven guidance to maximize pediatric TBM treatment while we await definitive trial results.
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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.