ArticleThe Journal of infectious diseases2025
The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.
Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
6 citing papers in PubMed.
- Successful Translational Prediction of Bedaquiline's Phase 2a Clinical Trial Results against Tuberculosis: The Zebrafish as a New Approach Methodology.Clinical pharmacology and therapeutics · 2026Article
- We Are Underprepared for Bedaquiline Resistance: A Call for Clinical and Programmatic Readiness.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2026Article
- Bedaquiline resistance: a predictable consequence of a game-changing drug?ASM case reports · 2026Article
- Small is big: growing impact of small molecule mass spectrometry in infectious disease drug development.mSphere · 2026Review
- A modeling-based framework to evaluate forgiveness of tuberculosis treatment in a BALB/c relapsing mouse model.Antimicrobial agents and chemotherapy · 2026Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors.
Funding
Abstract
backgroundCavitary tuberculosis is difficult to cure and constitutes a site of relapse. Bedaquiline has been a wonder drug in the treatment of multidrug-resistant tuberculosis, but emergence of resistance threatens the sustainability of its success. We designed site-of-disease pharmacokinetic studies to spatially resolve the penetration of bedaquiline, and 2 next-generation diarylquinolines, TBAJ876 and TBAJ587, in cavities.
methodsRabbits with established cavitary tuberculosis received the study drugs. A laser-capture microdissections scheme was developed to measure drug concentrations as a function of distance from blood supply in caseum. To simulate drug coverage in patient cavities, the data were modeled, and parameter estimates were linked to clinical plasma pharmacokinetic models.
resultsPharmacokinetic-pharmacodynamic simulations in caseum revealed that bedaquiline reaches steady state and efficacious concentrations in deep caseum after several weeks to months and lingers at subtherapeutic concentrations up to 3 years after therapy ends. TBAJ876 and TBAJ587, achieve bactericidal concentrations in caseum layers more rapidly and shorten the window of suboptimal concentrations post treatment compared to bedaquiline.
conclusionsThe slow kinetics of diffusion of bedaquiline into and out of caseum creates spatiotemporal windows of subtherapeutic concentrations. Site-of-disease simulations of TBAJ587 and TBAJ876 predict reduced opportunities for resistance development.
Indexed as
Identifiers
What OpenQuestion holds
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.