High-dose rifampicin to treat tuberculosis infection: potential and pitfalls

Scaling up effective, safe, short-course regimens to treat tuberculosis infection remains an important, but unmet priority to reduce the global burden of tuberculosis, which caused 10·6 million illnesses and 1·3 million deaths in 2022. 1 WHOGlobal Tuberculosis Report 2023. https://www.who.int/teams/global-tuberculosis-programme/tb-reportsDate: 2023 Date accessed: January 3, 2024 Google Scholar A randomised controlled trial published in The Lancet Respiratory Medicine by Rovina Ruslami and colleagues is the first to evaluate 2 months of high-dose rifampicin as a potential tuberculosis preventive treatment (TPT) regimen. 2 Ruslami R Fregonese F Apriani L et al. High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trial. Lancet Respir Med. 2024; (published online March 26.)https://doi.org/10.1016/S2213-2600(24)00076-6 Google Scholar Rifampicin is a key drug in the treatment of tuberculosis infection and tuberculosis disease. Although high-dose rifampicin (>10 mg/kg daily) has not yet enabled regimen shortening for the treatment of tuberculosis disease, previous studies have highlighted the potential of rifampicin while demonstrating adequate safety. 3 Jindani A Atwine D Grint D et al. Four-month high-dose rifampicin regimens for pulmonary tuberculosis. NEJM Evid. 2023; 2EVIDoa2300054 Crossref Google Scholar , 4 Boeree MJ Heinrich N Aarnoutse R et al. High-dose rifampicin, moxifloxacin, and SQ109 for treating tuberculosis: a multi-arm, multi-stage randomised controlled trial. Lancet Infect Dis. 2017; 17: 39-49 Summary Full Text Full Text PDF PubMed Scopus (260) Google Scholar High-dose, short-duration versus standard rifampicin for tuberculosis preventive treatment: a partially blinded, three-arm, non-inferiority, randomised, controlled trialIn this trial, 2 months of 30 mg/kg daily rifampicin had significantly worse safety and completion than 4 months of 10 mg/kg daily and 2 months of 20 mg/kg daily (the latter, a fully blinded comparison); we do not consider 30 mg/kg to be a good option for TPT. Rifampicin at 20 mg/kg daily for 2 months was as safe as standard treatment, but with lower completion. This difference remains unexplained. Full-Text PDF