Real-world treatment outcomes and adverse events during BPaLM therapy for rifampicin-resistant TB

Clinical trials have demonstrated high efficacy of bedaquiline, pretomanid, and linezolid with or without moxifloxacin (BPaLM/BPaL) for rifampicin-resistant and multidrug-resistant TB (RR/MDR-TB), but real-world implementation data remain limited, particularly from South-East Asian programmatic settings. We report Singapore's national experience with BPaLM/BPaL, focusing on treatment outcomes and adverse drug events.

We conducted a retrospective analysis of all RR/MDR-TB patients treated with BPaLM/BPaL at the National Tuberculosis Care Centre (NTBCC), Singapore, between July 2022 and September 2025. Data on demographics, microbiology, treatment characteristics, adverse drug reactions, and outcomes were extracted from a standing database.

Thirty-three patients were included (median age 39 years, 45.4% men). Over half were asymptomatic at diagnosis, and 90.9% had culture-confirmed disease. All patients who completed treatment locally achieved treatment success without any relapses observed during available follow-up. Adverse drug reactions requiring regimen modification occurred in 21 patients (63.6%). Moxifloxacin was discontinued for 14 patients (42.4%), predominantly due to QTc prolongation and gastrointestinal intolerance while 11 patients (33.3%) required linezolid dose reduction due to haematological toxicity and peripheral neuropathy.

BPaLM/BPaL achieved excellent early effectiveness but required frequent regimen modifications. Successful implementation of short-course RR/MDR-TB regimens requires anticipatory toxicity monitoring, flexible regimen management, and robust treatment support systems.