ArticleInternational journal of antimicrobial agents2014
PA-824 is as effective as isoniazid against latent tuberculosis infection in C3HeB/FeJ mice.
Article in International journal of antimicrobial agents, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Gene Regulatory Mechanism of Mycobacterium Tuberculosis during Dormancy.Current issues in molecular biology · 2024Review
- Delamanid or pretomanid? A Solomonic judgement!The Journal of antimicrobial chemotherapy · 2022Article
- Pretomanid for tuberculosis treatment: an update for clinical purposes.Current research in pharmacology and drug discovery · 2022Review
- Targeting Non-ReplicatingInternational journal of molecular sciences · 2021Review
- Population Pharmacokinetics and Bayesian Dose Adjustment to Advance TDM of Anti-TB Drugs.Clinical pharmacokinetics · 2021Review
- Profiling Pretomanid as a Therapeutic Option for TB Infection: Evidence to Date.Drug design, development and therapy · 2021Review
- Adjunctive Host-Directed Therapy With Statins Improves Tuberculosis-Related Outcomes in Mice.The Journal of infectious diseases · 2020Article
- Duration of pretomanid/moxifloxacin/pyrazinamide therapy compared with standard therapy based on time-to-extinction mathematics.The Journal of antimicrobial chemotherapy · 2020Article
- Improving treatment outcome assessment in a mouse tuberculosis model.Scientific reports · 2018Article
- Mice continue to be a good model for preliminary assessment of tuberculosis vaccine candidates.Human vaccines & immunotherapeutics · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The bicyclic nitroimidazole-like molecule PA-824 has activity both against replicating and hypoxic non-replicating Mycobacterium tuberculosis, raising the possibility that it may have a role in the treatment of latent tuberculosis infection (LTBI). This study aimed to examine the bactericidal and sterilising activities of PA-824 against LTBI in C3HeB/FeJ mice, which develop hypoxic, necrotic granulomas histologically resembling their human counterparts. Female 5-6-week-old C3HeB/FeJ mice were immunised via the aerosol route with a recombinant BCG strain overexpressing the 30-kDa major secretory protein (rBCG30) and were aerosol-infected 6 weeks later with virulent M. tuberculosis H37Rv. Six weeks after M. tuberculosis infection, separate groups of mice were left untreated (negative controls) or were treated with either rifampicin, isoniazid (INH) or PA-824. Culture-positive relapse was assessed in subgroups of mice after 2 months and 4 months of treatment. Human-equivalent doses of PA-824 given five times weekly showed similar bactericidal activity as INH at Months 1, 2 and 4 of treatment, and 15/15 mice treated with either PA-824 or INH showed lung-culture relapse 3 months after completion of treatment. To the best of our knowledge, this is the first report examining the sterilising activity of PA-824 in an animal model of LTBI. This model may be useful for screening the efficacy of novel drugs against LTBI, particularly those with specific activity against bacilli residing within necrotic lung granulomas.
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