High-dose rifampicin and clarithromycin for 4 weeks versus standard-dose rifampicin and clarithromycin for 8 weeks to treat Buruli ulcer: An open-label, individually randomized, controlled trial in Ghana
In brief
Four-week high-dose rifampicin did not speed Buruli ulcer bacterial clearance
In a Ghana trial of 42 people, viable bacteria cleared in an average of 4.9 weeks with four weeks of high-dose rifampicin and clarithromycin, versus 7.0 weeks with standard treatment; the difference was not statistically significant. No recurrences occurred, and the shorter regimen was well tolerated, but the small trial cannot establish whether it works as well or is safer.
- Journal
- PLoS neglected tropical diseases (Q1)
- Published
- 29 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Abigail Agbanyo, Yaw Ampem Amoako, Charles Opondo, Michael Ntiamoah Oppong, Adwoa Asante-Poku, Jacob Novignon, et al.
- PMID
- 42809592
- DOI
- 10.1371/journal.pntd.0014783
Why clinicians should know about it
- Picked for Microbiology (medical) (top studies of the week, 4 October 2026): Treatment trial, no diagnostic method focus
Abstract
BACKGROUND: The current 8-week regimen of rifampicin and clarithromycin for Buruli ulcer (BU) is suboptimal. High-dose rifampicin could shorten treatment and improve outcomes. We evaluated whether a 4-week high-dose regimen could improve time to clearance of viable Mycobacterium ulcerans. METHODOLOGY: In this open-label, individually randomised trial conducted in Ghana, participants with PCR-confirmed BU were assigned (1:1) to either high-dose oral rifampicin (20mg/kg) with clarithromycin (15mg/kg) for 4 weeks (HR) or standard-dose rifampicin (10mg/kg) with clarithromycin (15mg/kg) for 8 weeks (SR). All wounds were dressed with DACC-coated dressings. The primary outcome was time to clearance of viable M. ulcerans assessed by 16S rRNA qPCR up to week 20. FINDINGS: Between 26th November 2021 and 31st July 2024, 42 participants were randomised (HR:23, SR:19), which was short of the target (n = 112). The mean time to clearance was 4.9 weeks (SE 1.4) in the HR arm versus 7.0 weeks (SE 1.9) in the SR arm, with an adjusted mean difference of -0.5 weeks (95%CI -5.0 to 4.1, p = 0.835). No recurrences occurred in either arm. Paradoxical reactions were observed in 0/21 participants in the HR arm vs. 5/15 in the SR arm (adjusted OR 0.19, 95%CI 0.00-1.35, p = 0.102). Secondary infection rates were similar between groups. CONCLUSION: High‑dose rifampicin combination for 4 weeks was well tolerated in this population. A nominally lower proportion of paradoxical reactions was observed in the high-dose rifampicin arm compared with standard therapy. The trial did not find evidence of significantly shorter time to microbiological clearance or healing compared with standard therapy. Larger trials are needed to determine efficacy and safety. TRIAL REGISTRATION: Pan African Clinical Trials Repository, trial registration number: PACTR202011867644311 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=14534).
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.