ArticleAntimicrobial agents and chemotherapy2014
Reduced emergence of isoniazid resistance with concurrent use of thioridazine against acute murine tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Bioenergetic reprogramming of macrophages reduces drug tolerance in Mycobacterium tuberculosis.Nature communications · 2025Article
- A Comparative Pharmacokinetics Study of Orally and Intranasally Administered 8-Nitro-1,3-benzothiazin-4-one (BTZ043) Amorphous Drug Nanoparticles.ACS pharmacology & translational science · 2024Article
- In Vitro and In Vivo Antileishmanial Activity of Thioridazine.Acta parasitologica · 2024Article
- Investigating Combination Therapy as a Means to Enhance Activity and Repurpose Antimicrobials.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Functional Whole Genome Screen of Nutrient-StarvedMicroorganisms · 2023Article
- Targeting Prostate Cancer, the 'Tousled Way'.International journal of molecular sciences · 2023Review
- Adjunctive Host-Directed Therapy With Statins Improves Tuberculosis-Related Outcomes in Mice.The Journal of infectious diseases · 2020Article
- Antibiotic Treatment Shapes the Antigenic Environment During Chronic TB Infection, Offering Novel Targets for Therapeutic Vaccination.Frontiers in immunology · 2020Article
- The New Frontier of Host-Directed Therapies forFrontiers in immunology · 2020Review
- Bioenergetic Inhibitors: Antibiotic Efficacy and Mechanisms of Action inFrontiers in cellular and infection microbiology · 2020Review
- Targeting redox heterogeneity to counteract drug tolerance in replicatingScience translational medicine · 2019Article
- A Protein Complex from Human Milk Enhances the Activity of Antibiotics and Drugs againstAntimicrobial agents and chemotherapy · 2019Article
- Editorial: Alternative Therapeutics Against Antimicrobial-Resistant Pathogens.Frontiers in microbiology · 2019Article
- Evolution of drug resistance in Mycobacterium tuberculosis: a review on the molecular determinants of resistance and implications for personalized care.The Journal of antimicrobial chemotherapy · 2018Review
- Metformin Adjunctive Therapy Does Not Improve the Sterilizing Activity of the First-Line Antitubercular Regimen in Mice.Antimicrobial agents and chemotherapy · 2017Article
- Article
- Thioridazine: A Non-Antibiotic Drug Highly Effective, in Combination with First Line Anti-Tuberculosis Drugs, against Any Form of Antibiotic Resistance of Mycobacterium tuberculosis Due to Its Multi-Mechanisms of Action.Antibiotics (Basel, Switzerland) · 2017Review
- Interplay between Mutations and Efflux in Drug Resistant Clinical Isolates ofFrontiers in microbiology · 2017Article
- Stringent Response Factors PPX1 and PPK2 Play an Important Role in Mycobacterium tuberculosis Metabolism, Biofilm Formation, and Sensitivity to Isoniazid In Vivo.Antimicrobial agents and chemotherapy · 2016Article
- Thioridazine as Chemotherapy for Mycobacterium avium Complex Diseases.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The repurposing of existing drugs is being pursued as a means by which to accelerate the development of novel regimens for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). In the current study, we assessed the activity of the antipsychotic drug thioridazine (TRZ) in combination with the standard regimen in a well-validated murine TB model. Single-dose and steady-state pharmacokinetic studies were performed in BALB/c mice to establish human-equivalent doses of TRZ. To determine the bactericidal activity of TRZ against TB in BALB/c mice, three separate studies were performed, including a dose-ranging study of TRZ monotherapy and efficacy studies of human-equivalent doses of TRZ with and without isoniazid (INH) or rifampin (RIF). Therapeutic efficacy was assessed by the change in mycobacterial load in the lung. The human-equivalent dose of thioridazine was determined to be 25 mg/kg of body weight, which was well tolerated in mice. TRZ was found to accumulate at high concentrations in lung tissue relative to serum levels. We observed modest synergy during coadministration of TRZ with INH, and the addition of TRZ reduced the emergence of INH-resistant mutants in mouse lungs. In conclusion, this study further illustrates the opportunity to reevaluate the contribution of TRZ to the sterilizing activity of combination regimens to prevent the emergence of drug-resistant M. tuberculosis.
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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.