Can 6-month long regimens become the standardized treatment for MDR-TB globally?

Abstract

Treatment for multidrug/rifampicin resistant (MDR/RR) tuberculosis (TB) was traditionally long and poorly tolerated. In 2022, WHO recommended the first 6-month regimen (BPaLM), followed in 2025 by a second short-course option (BDLLfxC) with potential drastic improvement of treatment outcome. The BDLLfxC regimen addresses key gaps in target populations, including groups for whom BPaLM is not indicated: children of any age, adolescents, and pregnant and breastfeeding women (PBFW). A key difference between the two regimens is the replacement of pretomanid with delamanid in the BDLLfxC. However, limitations remain. Neither BPaLM nor BDLLfxC are recommended in patients with complicated forms of extrapulmonary MDR-TB: central nervous system (CNS), osteoarticular (OA) and disseminated disease. The problem is twofold: from one side there are theoretical pharmacokinetic/pharmacodynamic reasons for lower concentrations of the active principles at these sites, from the other side clinical experience is virtually absent in such cases. In this narrative review, we explore the use of 6-month regimens for MDR/RR-TB in specific populations - children, PBFW, people living with HIV, and those with challenging TB forms (e.g., CNS, bone, disseminated). The overall aim is to discuss how far we still are from the goal of a public health approach to the treatment of MDR-TB.