ArticleAntimicrobial agents and chemotherapy2016
Investigation of Elimination Rate, Persistent Subpopulation Removal, and Relapse Rates of Mycobacterium tuberculosis by Using Combinations of First-Line Drugs in a Modified Cornell Mouse Model.
Article in Antimicrobial agents and chemotherapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Beyond culturability: VBNC-like and differentially culturableFrontiers in cellular and infection microbiology · 2026Review
- Using Dynamic Oral Dosing of Rifapentine and Rifabutin to Simulate Exposure Profiles of Long-Acting Formulations in a Mouse Model of Tuberculosis Preventive Therapy.Antimicrobial agents and chemotherapy · 2023Article
- Eradication of Drug-TolerantMicroorganisms · 2023Review
- Using dynamic oral dosing of rifapentine and rifabutin to simulate exposure profiles of long-acting formulations in a mouse model of tuberculosis preventive therapy.bioRxiv : the preprint server for biology · 2023Article
- Bacterial growth dynamics and pharmacokinetic-pharmacodynamic relationships of rifampicin and bedaquiline in BALB/c mice.British journal of pharmacology · 2022Article
- Culture-Free Enumeration ofMicroorganisms · 2022Article
- Article
- Review
- Re-growth ofAntimicrobial agents and chemotherapy · 2019Article
- Article
- Moxifloxacin Replacement in Contemporary Tuberculosis Drug Regimens Is Ineffective against Persistent Mycobacterium tuberculosis in the Cornell Mouse Model.Antimicrobial agents and chemotherapy · 2018Article
- Rifamycin action on RNA polymerase in antibiotic-tolerantProceedings of the National Academy of Sciences of the United States of America · 2017Article
- De Novo Emergence of Genetically Resistant Mutants of Mycobacterium tuberculosis from the Persistence Phase Cells Formed against Antituberculosis Drugs In Vitro.Antimicrobial agents and chemotherapy · 2017Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, the most effective tuberculosis control method involves case finding and 6 months of chemotherapy. There is a need to improve our understanding about drug interactions, combination activities, and the ability to remove persistent bacteria using the current regimens, particularly in relation to relapse. We aimed to investigate the therapeutic effects of three main components, rifampin (RMP), isoniazid (INH), and pyrazinamide (PZA), in current drug regimens using a modified version of the Cornell mouse model. We evaluated the posttreatment levels of persistent Mycobacterium tuberculosis in the organs of mice using culture filtrate derived from M. tuberculosis strain H37Rv. When RMP was combined with INH, PZA, or INH-PZA, significant additive activities were observed compared to each of the single-drug treatments. However, the combination of INH and PZA showed a less significant additive effect than either of the drugs used on their own. Apparent culture negativity of mouse organs was achieved at 14 weeks of treatment with RMP-INH, RMP-PZA, and RMP-INH-PZA, but not with INH-PZA, when conventional tests, namely, culture on solid agar and in liquid broth, indicated that the organs were negative for bacteria. The relapse rates for RMP-containing regimens were not significantly different from a 100% relapse rate at the numbers of mice examined in this study. In parallel, we examined the organs for the presence of culture filtrate-dependent persistent bacilli after 14 weeks of treatment. Culture filtrate treatment of the organs revealed persistent M. tuberculosis Modeling of mycobacterial elimination rates and evaluation of culture filtrate-dependent organisms showed promise as surrogate methods for efficient factorial evaluation of drug combinations in tuberculosis in mouse models and should be further evaluated against relapse. The presence of culture filtrate-dependent persistent M. tuberculosis is the likely cause of disease relapse in this modified Cornell mouse model.
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