ArticleAntimicrobial agents and chemotherapy2018
Impact of Clofazimine Dosing on Treatment Shortening of the First-Line Regimen in a Mouse Model of Tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Model-Based Meta-Analysis of Relapsing Mouse Model Studies from the Critical Path to Tuberculosis Drug Regimens Initiative Database.Antimicrobial agents and chemotherapy · 2022Pooled it
- Treatment of Drug-Resistant Tuberculosis. An Official ATS/CDC/ERS/IDSA Clinical Practice Guideline.American journal of respiratory and critical care medicine · 2019Guideline
- A 3-month clofazimine-rifapentine-containing regimen for drug-susceptible tuberculosis versus standard of care (Clo-Fast): a randomised, open-label, phase 2c clinical trial.The Lancet. Infectious diseases · 2026Trial
- An exploratory, qualitative study of treatment preferences among participants in a TB therapeutic trial.IJTLD open · 2026Article
- Quality-by-Design Development of a Clofazimine-Pyrazinamide Dermal Emulsion and Its Diffusion Behavior in Strat-MPharmaceuticals (Basel, Switzerland) · 2026Article
- RP-DAD-HPLC Method for Quantitative Analysis of Clofazimine and Pyrazinamide for Inclusion in Fixed-Dose Combination Topical Drug Delivery System.Methods and protocols · 2026Article
- "Six months is a lot of time to lie": Anticipated stigma, disclosure and treatment preferences among participants in a tuberculosis therapeutic trial.Research square · 2025Article
- REVOLUTIONIZING TUBERCULOSIS REGIMEN DEVELOPMENT.Transactions of the American Clinical and Climatological Association · 2025Review
- Spectinamide MBX-4888A exhibits favorable lesion and tissue distribution and promotes treatment shortening in advanced murine models of tuberculosis.Antimicrobial agents and chemotherapy · 2024Article
- Therapeutic drug monitoring in tuberculosis.European journal of clinical pharmacology · 2024Review
- Shortened Treatment Regimens for Drug Sensitive TB.Indian journal of pediatrics · 2024Review
- Clofazimine as a substitute for rifampicin improves efficacy ofAntimicrobial agents and chemotherapy · 2024Article
- Advanced drug delivery and therapeutic strategies for tuberculosis treatment.Journal of nanobiotechnology · 2023Review
- Development of a HPLC Method for Analysis of a Combination of Clofazimine, Isoniazid, Pyrazinamide, and Rifampicin Incorporated into a Dermal Self-Double-Emulsifying Drug Delivery System.Methods and protocols · 2023Article
- Spontaneous mutational patterns and novel mutations for bedaquiline and clofazimine resistance inMicrobiology spectrum · 2023Article
- The Development of Dermal Self-Double-Emulsifying Drug Delivery Systems: Preformulation Studies as the Keys to Success.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Eradication of Drug-TolerantMicroorganisms · 2023Review
- Updated considerations in the diagnosis and management of tuberculosis infection and disease: integrating the latest evidence-based strategies.Expert review of anti-infective therapy · 2023Review
- Clofazimine for the treatment of tuberculosis.Frontiers in pharmacology · 2023Review
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
The antileprosy drug clofazimine was recently repurposed as part of a newly endorsed short-course regimen for multidrug-resistant tuberculosis. It also enables significant treatment shortening when added to the first-line regimen for drug-susceptible tuberculosis in a mouse model. However, clofazimine causes dose- and duration-dependent skin discoloration in patients, and the optimal clofazimine dosing strategy in the context of the first-line regimen is unknown. We utilized a well-established mouse model to systematically address the impacts of duration, dose, and companion drugs on the treatment-shortening activity of clofazimine in the first-line regimen. In all studies, the primary outcome was relapse-free cure (culture-negative lungs) 6 months after stopping treatment, and the secondary outcome was bactericidal activity, i.e., the decline in the lung bacterial burden during treatment. Our findings indicate that clofazimine activity is most potent when coadministered with first-line drugs continuously throughout treatment and that equivalent treatment-shortening results are obtained with half the dose commonly used in mice. However, our studies also suggest that clofazimine at low exposures may have negative impacts on treatment outcomes, an effect that was evident only after the first 3 months of treatment. These data provide a sound evidence base to inform clofazimine dosing strategies to optimize the antituberculosis effect while minimizing skin discoloration. The results also underscore the importance of conducting long-term studies to allow the full evaluation of drugs administered in combination over long durations.
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