High-dose bedaquiline for XDR-TB: Initial safety data from the MDR-TB network
Coordinated by the DZK, data on individual treatment attempts were collected within the framework of the MDR tuberculosis network for five patients with extensively drug-resistant (XDR) tuberculosis (TB) and rv0678 mutations for whom no treatment options were available within the national and international recommendations.
This retrospective case series investigated the safety of high-dose bedaquiline therapy. QTc prolongations were documented, but these were often attributable to cumulative effects of combination therapies, particularly high-dose levofloxacin. No relevant increase in hepatotoxicity was observed.
Since the available data do not allow conclusions to be drawn about the effectiveness of the dose increase, this off-label approach should only be considered in the absence of alternative therapies, after careful consideration of the benefits and risks, informed consent, and intensified monitoring of the QTc interval. Clinical studies will be necessary to confirm the safety and efficacy of this approach.
For XDR-TB cases, the WHO and German guidelines recommend an individualized approach based on the results of resistance testing. Due to a lack of data and the small number of cases, the individual design of the therapy is left to experts and therapy centers. The DZK is participating in the BETTER project, which developed a practical guide for XDR-TB in 2025. Based on literature research and expert opinions, this guide compiles information on increasing the dosage of second-line drugs for cases with limited therapeutic options (1).
Detailed information on the high-dose bedaquiline case series can be found in the publication in the European Respiratory Journal (ERJ) and can be requested from the authors.
1. Nkomo T, Udwadia Z, Vambe D, et al. Clinical best practices for caring for people with expanded resistance to newer TB drugs. Int J Tuberc Lung Dis Open 2025; 2: 315–323.
This study was kindly supported financially by the Oskar-Helene-Heim Foundation and the Günther Labes Foundation.
