ArticleThe Journal of antimicrobial chemotherapy2017
Modelling of mycobacterial load reveals bedaquiline's exposure-response relationship in patients with drug-resistant TB.
Article in The Journal of antimicrobial chemotherapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04062201 (An Open Label, Randomized Controlled Trial to Establish the Efficacy and Safety of a Study Strategy Consisting of 6 Months of Bedaquiline), which is not on this map. Cited by 39 papers.
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.
An Open Label, Randomized Controlled Trial to Establish the Efficacy and Safety of a Study Strategy Consisting of 6 Months of Bedaquiline (BDQ), Delamanid (DLM), and Linezolid (LNZ), With Levofloxacin (LVX) and Clofazimine (CFZ) Compared to the Current South African Standard of Care (Control Strategy) for 9 Months for the Treatment of Rifampicin Resistant Tuberculosis (RR-TB)
Who cites it
39 citing papers in PubMed.
- Population pharmacokinetics and exposure-response relationship of the antituberculosis drug BTZ-043.The Journal of antimicrobial chemotherapy · 2025Trial
- A pharmacometric multistate model for predicting long-term treatment outcomes of patients with pulmonary TB.The Journal of antimicrobial chemotherapy · 2024Trial
- Trial
- Exposure-safety analysis of QTc interval and transaminase levels following bedaquiline administration in patients with drug-resistant tuberculosis.CPT: pharmacometrics & systems pharmacology · 2021Trial
- Evaluation of six months sputum culture conversion as a surrogate endpoint in a multidrug resistant-tuberculosis trial.PloS one · 2018Trial
- Bedaquiline reloading strategies following interruptions during daily dosing.Antimicrobial agents and chemotherapy · 2026Article
- Insights into the Role of Rifampicin Exposure and Clinical Baseline Covariates on the Response to Pulmonary Tuberculosis Treatment.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- An Interactive Pharmacokinetic-Pharmacodynamic Framework to Evaluate Bedaquiline Dose Modifications in Adults With Tuberculosis.CPT: pharmacometrics & systems pharmacology · 2026Article
- Bedaquiline pharmacokinetics in drug-resistant tuberculosis: from exposure variability to individualized therapy.Frontiers in pharmacology · 2026Review
- Improving the efficiency of drug resistant tuberculosis treatment trials: a time-to-event alternative marker for bacteriological response and adaptive minimization for randomization.BMC medical research methodology · 2025Article
- Model-Informed Once-Daily Dosing Strategy for Bedaquiline and Delamanid in Children, Adolescents and Adults with Tuberculosis.Clinical pharmacology and therapeutics · 2025Article
- Development and validation of a time-varying correction factor for QT interval assessment in drug-resistant tuberculosis patients.International journal of antimicrobial agents · 2025Article
- Multidrug-resistant tuberculosis.Nature reviews. Disease primers · 2024Review
- Power to identify exposure-response relationships in phase IIa pulmonary tuberculosis trials with multi-dimensional bacterial load modeling.CPT: pharmacometrics & systems pharmacology · 2024Article
- Combined quantitative tuberculosis biomarker model for time-to-positivity and colony forming unit to support tuberculosis drug development.Frontiers in pharmacology · 2023Article
- Population pharmacokinetics and model-based dosing evaluation of bedaquiline in multidrug-resistant tuberculosis patients.Frontiers in pharmacology · 2023Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Population Pharmacokinetic Modeling of Bedaquiline among Multidrug-Resistant Pulmonary Tuberculosis Patients from China.Antimicrobial agents and chemotherapy · 2022Article
- Article
- Development and Validation of a Nomogram for Prediction of QT Interval Prolongation in Patients Administered Bedaquiline-Containing Regimens in China: a Modeling Study.Antimicrobial agents and chemotherapy · 2022Article
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBedaquiline has been shown to reduce time to sputum culture conversion (SCC) and increase cure rates in patients with drug-resistant TB, but the influence of drug exposure remains uncharacterized.
objectivesTo investigate whether an exposure-response relationship could be characterized by making better use of the existing information on pharmacokinetics and longitudinal measurements of mycobacterial load.
methodsQuantitative culture data in the form of time to positivity (TTP) in mycobacterial growth indicator tubes obtained from a randomized placebo-controlled Phase IIb registration trial were examined using non-linear mixed-effects methodology. The link to individual bedaquiline exposures and other patient characteristics was evaluated.
resultsThe developed model included three simultaneously fitted components: a longitudinal representation of mycobacterial load in patients, a probabilistic component for bacterial presence in sputum samples, and a time-to-event model for TTP. Data were described adequately, and time to SCC was well predicted. Individual bedaquiline exposure was found to significantly affect the decline in mycobacterial load. Consequently, the proportion of patients without SCC at week 20 is expected to decrease from 25% (95% CI 20%-31%) without bedaquiline to 17% (95% CI 13%-21%), 12% (95% CI 8%-16%) and 7% (95% CI 4%-11%), respectively, with half the median, median and double the median bedaquiline exposure observed in patients with standard dosing. Baseline bacterial load and level of drug resistance were other important predictors.
conclusionsTo our knowledge, this is the first successful description of bedaquiline's exposure-response relationship and may be used when considering dose optimization. Characterization of this relationship was possible by integrating quantitative information in existing clinical data using novel models.
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