Bedaquiline-pretomanid-linezolid as a bridging therapy for adverse events in drug-sensitive tuberculosis

Bedaquiline-pretomanid-linezolid (BPaL) and other new short course regimens have been a major advance in the treatment of multidrug-resistant (MDR-TB) and, particularly, pre-extensively drug-resistant tuberculosis (preXDR-TB). In contrast, treatment options for drug-sensitive tuberculosis (DS-TB) have remained almost unchanged for decades. There is scant evidence on the use of new antituberculous drugs in DS-TB, but first trials suggest they could be efficient. Many DS-TB patients suffer from mild to severe toxicities during first-line therapy with isoniazid-rifampicin-pyrazinamide-ethambutol (HRZE), with hepatotoxicity being the most common and treatment-limiting adverse event (AE). Still, there is a lack of detailed protocols for managing AEs in DS-TB care. We have been using BPaL as a bridging regimen in highly symptomatic DS-TB patients with severe AE due to HRZE. From 01/2018 to 03/2025, 34 (12%) out of 277 DS-TB inpatients at our tertiary care center experienced AE Grade 3-4 to HRZE. From 2018 to 2022, patients received treatment interruption and re-exposure when AEs abated, none received an alternative bridging regimen. Since 07/2023, when BPaL was easily available in Germany, in 14 patients with pulmonary or extrapulmonary DS-TB HRZE was paused, and the treatment was continued with BPaL until AEs resolved, and HRZE was then reestablished. In both conditions, HRZE was reestablished in step-wise dose escalation according to the national guideline (with BPaL continued until full HRZE dosing). All BPaL-treated patients have successfully completed their therapy. There have been no relevant AEs, treatment failure, recurrence, or TB-associated death. Patients who received BPaL bridging had numerically shorter mean time to sputum conversion, inpatient stay was numerically shorter, and treatment completion and cure rates were higher in the bridging group. In the BPaL group no TB complications (surgery, ICU admission, death) occurred. In conclusion, patients with HRZE-associated AEs and a high need for efficient TB therapy treated with BPaL had favourable outcomes, without relevant drug accumulation or toxicities to BPaL in patients with impaired hepatic function. BPaL could add a valuable treatment option for selected patients with DS-TB and HRZE-associated AEs. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany