ArticleACS infectious diseases2016
Bedaquiline and Pyrazinamide Treatment Responses Are Affected by Pulmonary Lesion Heterogeneity in
Article in ACS infectious diseases, 2016. 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 111 papers, 1 of them a synthesis that pooled it.
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.
Pharmacometrics to Advance Novel Regimens for Drug-resistant Tuberculosis
Who cites it
111 citing papers in PubMed, 1 synthesis or guideline pooled it, 153 citations in OpenAlex.
- Studying intrapulmonary pharmacokinetics for tuberculosis treatment: a systematic review of methodology.The Journal of antimicrobial chemotherapy · 2025Pooled it
- Prospectively predicting BPaMZ phase IIb/III trial outcomes using a translational mouse-to-human platform.Antimicrobial agents and chemotherapy · 2024Trial
- Targeting Latent Tuberculosis Using Hypoxia-Activated Prodrugs of Bedaquiline Analogues.ACS medicinal chemistry letters · 2026Article
- MakingCell insight · 2026Review
- Fast-growing intracellular Mycobacterium tuberculosis populations evade antibiotic treatment.Nature communications · 2026Article
- Combination strategies targeting multiple ETC subunits as a rational approach for drug-resistant TB therapy.Archives of microbiology · 2026Review
- Regenerative therapeutics for chronic obstructive pulmonary disease.Pharmacological reviews · 2026Review
- Physiologic recovery of Mycobacterium tuberculosis from drug injury: A molecular study of post antibiotic effect in vitro and in vivo.PLoS pathogens · 2026Article
- Adaptive immunity shapes baseline physiology ofbioRxiv : the preprint server for biology · 2026Article
- Mouse models of tuberculosis uniformly featuring hypoxic necrotic lesions and poor response to chemotherapy.Infection and immunity · 2026Article
- A modeling-based framework to evaluate forgiveness of tuberculosis treatment in a BALB/c relapsing mouse model.Antimicrobial agents and chemotherapy · 2026Article
- Essential role of MHC II in the antitubercular efficacy of pyrazinamide.Antimicrobial agents and chemotherapy · 2026Article
- Repeated pulmonary dosing of β-glucan-chitosan-PLGA nanoparticles controlsAntimicrobial agents and chemotherapy · 2026Article
- Article
- Immunopathological outcomes are isolate dependent in chronic Mycobacterium avium complex pulmonary disease.Disease models & mechanisms · 2026Article
- Bedaquiline Resistance and Treatment Outcomes Among Patients With Tuberculosis Previously Exposed to Bedaquiline in India: A Multicentric Retrospective Cohort Study.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Extrapolation of lung pharmacokinetics of bedaquiline across species using physiologically-based pharmacokinetic modelling.British journal of clinical pharmacology · 2025Article
- Mouse Models Uniformly Featuring Human-like Lesions Harboring Drug-tolerantbioRxiv : the preprint server for biology · 2025Article
- The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.The Journal of infectious diseases · 2025Article
- Contribution of front-line, standard-of-care drugs to bactericidal responses, resistance emergence, and cure in murine models of easy- or hard-to-treat tuberculosis disease.Antimicrobial agents and chemotherapy · 2025Article
51 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
BALB/c and Swiss mice are routinely used to validate the effectiveness of tuberculosis drug regimens, although these mouse strains fail to develop human-like pulmonary granulomas exhibiting caseous necrosis. Microenvironmental conditions within human granulomas may negatively impact drug efficacy, and this may not be reflected in non-necrotizing lesions found within conventional mouse models. The C3HeB/FeJ mouse model has been increasingly utilized as it develops hypoxic, caseous necrotic granulomas which may more closely mimic the pathophysiological conditions found within human pulmonary granulomas. Here, we examined the treatment response of BALB/c and C3HeB/FeJ mice to bedaquiline (BDQ) and pyrazinamide (PZA) administered singly and in combination. BALB/c mice consistently displayed a highly uniform treatment response to both drugs, while C3HeB/FeJ mice displayed a bimodal response composed of responsive and less-responsive mice. Plasma pharmacokinetic analysis of dissected lesions from BALB/c and C3HeB/FeJ mice revealed that PZA penetrated lesion types from both mouse strains with similar efficiency. However, the pH of the necrotic caseum of C3HeB/FeJ granulomas was determined to be 7.5, which is in the range where PZA is essentially ineffective under standard laboratory in vitro growth conditions. BDQ preferentially accumulated within the highly cellular regions in the lungs of both mouse strains, although it was present at reduced but still biologically relevant concentrations within the central caseum when dosed at 25 mg/kg. The differential treatment response which resulted from the heterogeneous pulmonary pathology in the C3HeB/FeJ mouse model revealed several factors which may impact treatment efficacy, and could be further evaluated in clinical trials.
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.