ArticleFrontiers in microbiology2015
High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo.
Article in Frontiers in microbiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05169554 (Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy), which is not on this map. Cited by 67 papers, 1 of them a synthesis 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.
Beta-Lactam Containing Regimen for the Shortening of Buruli Ulcer Disease Therapy: Comparison of 8 Weeks Standard Therapy (Rifampicin Plus Clarithromycin) vs. 4 Weeks Standard Plus Amoxicillin/Clavulanate Therapy [RC8 vs. RCA4]
Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Pooled it
- Model-based evaluation of the interaction between ritonavir-boosted atazanavir and rifampicin in Ugandan adults with HIV.British journal of clinical pharmacology · 2025Trial
- Treatment and recurrence on re-treatment tuberculosis patients: a randomized clinical trial and 7-year perspective cohort study in China.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2020Trial
- Pharmacokinetics, Tolerability, and Bacteriological Response of Rifampin Administered at 600, 900, and 1,200 Milligrams Daily in Patients with Pulmonary Tuberculosis.Antimicrobial agents and chemotherapy · 2017Trial
- High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial.The Lancet. Infectious diseases · 2017Trial
- Article
- A new Persister Enrichment Model inbioRxiv : the preprint server for biology · 2026Article
- Efficacy and safety of daily drug regimens containing high-dose versus standard-dose rifampicin for treating pulmonary tuberculosis: Systematic review and meta-analysis.Lung India : official organ of Indian Chest Society · 2026Article
- Article
- Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis.Communications biology · 2024Article
- Eradication of Drug-TolerantMicroorganisms · 2023Review
- L-Tyrosine Limits Mycobacterial Survival in Tuberculous Granuloma.Pathogens (Basel, Switzerland) · 2023Article
- High rifampicin peak plasma concentrations accelerate the slow phase of bacterial decline in tuberculosis patients: Evidence for heteroresistance.PLoS computational biology · 2023Article
- Intranasal multivalent adenoviral-vectored vaccine protects against replicating and dormant M.tb in conventional and humanized mice.NPJ vaccines · 2023Article
- Tuberculosis Molecular Bacterial Load Assay Reveals Early Delayed Bacterial Killing in Patients With Relapse.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Comparison ofFrontiers in microbiology · 2023Article
- A Bibliometric Analysis of Research on Bacterial Persisters.BioMed research international · 2023Article
- New and Repurposed Drugs for the Treatment of Active Tuberculosis: An Update for Clinicians.Respiration; international review of thoracic diseases · 2023Review
- Article
- Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although high-dose rifampicin holds promise for improving tuberculosis control by potentially shortening treatment duration, these effects attributed to eradication of persistent bacteria are unclear. The presence of persistent Mycobacterium tuberculosis was examined using resuscitation promoting factors (RPFs) in both in vitro hypoxia and in vivo murine tuberculosis models before and after treatment with incremental doses of rifampicin. Pharmacokinetic parameters and dose-dependent profile of rifampicin in the murine model were determined. The Cornell mouse model was used to test efficacy of high-dose rifampicin in combination with isoniazid and pyrazinamide and to measure relapse rate. There were large numbers of RPF-dependent persisters in vitro and in vivo. Stationary phase cultures were tolerant to rifampicin while higher concentrations of rifampicin eradicated plate count positive but not RPF-dependent persistent bacteria. In murine infection model, incremental doses of rifampicin exhibited a dose-dependent eradication of RPF-dependent persisters. Increasing the dose of rifampicin significantly reduced the risk of antibiotic resistance emergence. In Cornell model, mice treated with high-dose rifampicin regimen resulted in faster visceral clearance; organs were M. tuberculosis free 8 weeks post-treatment compared to 14 weeks with standard-dose rifampicin regimen. Organ sterility, plate count and RPF-dependent persister negative, was achieved. There was no disease relapse compared to the standard dose regimen (87.5%). High-dose rifampicin therapy results in eradication of RPF-dependent persisters, allowing shorter treatment duration without disease relapse. Optimizing rifampicin to its maximal efficacy with acceptable side-effect profiles will provide valuable information in human studies and can potentially improve current tuberculosis chemotherapy.
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What OpenQuestion holds
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.