ArticleAntimicrobial agents and chemotherapy2023
Next-Generation Diarylquinolines Improve Sterilizing Activity of Regimens with Pretomanid and the Novel Oxazolidinone TBI-223 in a Mouse Tuberculosis Model.
Article in Antimicrobial agents and chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Pharmacokinetics, tolerability, and safety of TBI-223, a novel oxazolidinone, in healthy participants.Antimicrobial agents and chemotherapy · 2025Trial
- Semi-Mechanistic Joint Population Pharmacokinetic Modeling of the Novel Antituberculosis Drug Sorfequiline and Its Metabolite M3 in Healthy Volunteers.CPT: pharmacometrics & systems pharmacology · 2026Article
- Population pharmacokinetics of TBAJ-587 and its main metabolites-Evaluation of different loading dose strategies and early dose selection.British journal of clinical pharmacology · 2026Article
- Article
- The Structure, Properties, and Clinical Utility of Contezolid for Antituberculosis: A Narrative Review.Infectious diseases and therapy · 2026Review
- Characterization of new mouse models of acute and chronicAntimicrobial agents and chemotherapy · 2025Article
- The Kinetics of Bedaquiline Diffusion in Tuberculous Cavities Open a Window for the Emergence of Resistance.The Journal of infectious diseases · 2025Article
- Article
- Evolution of Small Molecule Inhibitors ofJournal of medicinal chemistry · 2025Article
- Contribution of telacebec to novel drug regimens in a murine tuberculosis model.Antimicrobial agents and chemotherapy · 2025Article
- Relative Contributions of the Novel Diarylquinoline TBAJ-876 and its Active Metabolite to the Bactericidal Activity in a Murine Model of Tuberculosis.The Journal of infectious diseases · 2024Article
- TBAJ-587, a novel diarylquinoline, is active againstAntimicrobial agents and chemotherapy · 2024Article
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- A modified BPaL regimen for tuberculosis treatment replaces linezolid with inhaled spectinamides.eLife · 2024Article
- Projected health and economic effects of a pan-tuberculosis treatment regimen: a modelling study.The Lancet. Global health · 2024Article
- Dose optimization of TBI-223 for enhanced therapeutic benefit compared to linezolid in antituberculosis regimen.Nature communications · 2024Article
- Dynamic PET reveals compartmentalized brain and lung tissue antibiotic exposures of tuberculosis drugs.Nature communications · 2024Observational
- New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?Pharmaceutics · 2024Review
- Use of multiple pharmacodynamic measures to deconstruct the Nix-TB regimen in a short-course murine model of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Bactericidal and sterilizing activity of novel regimens combining bedaquiline or TBAJ-587 with GSK2556286 and TBA-7371 in a mouse model of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A regimen comprised of bedaquiline (BDQ, or B), pretomanid, and linezolid (BPaL) is the first oral 6-month regimen approved by the U.S. Food and Drug Administration and recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis. We used a well-established BALB/c mouse model of tuberculosis to evaluate the treatment-shortening potential of replacing bedaquiline with either of two new, more potent diarylquinolines, TBAJ-587 and TBAJ-876, in early clinical trials. We also evaluated the effect of replacing linezolid with a new oxazolidinone, TBI-223, exhibiting a larger safety margin with respect to mitochondrial toxicity in preclinical studies. Replacing bedaquiline with TBAJ-587 at the same 25-mg/kg dose significantly reduced the proportion of mice relapsing after 2 months of treatment, while replacing linezolid with TBI-223 at the same 100-mg/kg dose did not significantly change the proportion of mice relapsing. Replacing linezolid or TBI-223 with sutezolid in combination with TBAJ-587 and pretomanid significantly reduced the proportion of mice relapsing. In combination with pretomanid and TBI-223, TBAJ-876 at 6.25 mg/kg was equipotent to TBAJ-587 at 25 mg/kg. We conclude that replacement of bedaquiline with these more efficacious and potentially safer diarylquinolines and replacement of linezolid with potentially safer and at least as efficacious oxazolidinones in the clinically successful BPaL regimen may lead to superior regimens capable of treating both drug-susceptible and drug-resistant TB more effectively and safely.
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