BPaL in RR/MDR/preXDR-TB and Extensive Disease: Real-World-Outcomes from a German Cohort

New antituberculosis drugs like bedaquilin (BDQ) and pretomanid (PTM) have transformed the treatment landscape for drug-resistant tuberculosis (DR-TB). Bedaquilin-pretomanid-linezolid (BPaL) is currently the only three-drug, all-oral, six-month treatment approved for pre-extensively drug-resistant tuberculosis (preXDR-TB). Since 2022, we have applied six-months of BPaL beyond this indication in any patient with rifamycin resistance, including extensive disease. Currently, the WHO guideline and German national guideline limit the three drug-regimen BPaL to preXDR-TB, whereas in multidrug-resistant tuberculosis (MDR-TB), the four-drug-regimen bedaquilin-pretomanid-linezolid-moxifloxacin (BPaLM), or even five-drug-regimens are suggested, and longer therapies are oftentimes used in extensive cases. Here, we report the outcome of our cohort of pulmonary and extrapulmonary RR/MDR- and preXDR-TB treated with BPaL with a follow-up of up to two years. Between 09/2022 and 04/2025, 30 patients with pulmonary or extrapulmonary RR/MDR- or preXDR-TB were treated with BPaL for 6 months at our center. 50% had preXDR-TB, 46% MDR-TB, and 3% RR-TB. Extensive disease—defined as cavitary, bilateral, or disseminated TB—was present in 40% of patients. Of 30 patients, 26 (87%) successfully completed their treatment, and two are still on therapy, yet showing clinical, radiological, and microbiological improvement, and two patients were lost to follow-up because they decided to return to their country of origin during treatment. Until now, there has been no treatment failure, recurrence, acquired resistance or TB-associated death (mean time from diagnosis to most recent follow-up 13 (1-30) months). In conclusion, this real-world cohort supports the safe and effective use of BPaL for RR/MDR/pre-XDR-TB, including patients with prior exposure to BDQ/LZD and extensive disease. Broader availability of PTM and implementation of this regimen, particularly as a fluoroquinolone- and clofazimine-sparing strategy, may improve DR-TB outcomes. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany