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Randomized Controlled Trial
. 2025 Jul;91(1):106509.
doi: 10.1016/j.jinf.2025.106509. Epub 2025 May 15.

Long term outcomes in drug resistant tuberculosis with Bedaquiline, Pretomanid and varying doses of Linezolid

Bella Devaleenal Daniel  1 , Sivakumar Shanmugam  2 , Rashi Mehta  3 , Manpreet Bhalla  4 , Muthuvijayalakshmi Mariappan  2 , Balaji Ramraj  5 , Avijit Kumar Awasthi  6 , Pranav Patel  7 , Amita Jain  8 , Parul Jain  8 , Chetan Kumar  9 , Vikas Oswal  10 , Neeta Singla  4 , Santosh Kumar  11 , Jigna Dave  12 , Parul Vadgama  13 , Anuj K Bhatnagar  14 , Surya Kant  8 , Rathinam Prabhakaran  15 , Grinish Tamakuwala  13 , Rishikesh Nath Mukherjee  14 , Ramesh Kumar Santhanakrishnan  2 , Dhandapani Ravikumar  2 , Naveen Kumar Nagarajan  2 , Shanmugapriya Kumaravadivelu  2 , Jeyadeepa Bharathi  2 , Anand Sridhar  16 , Ranjani Ramachandran  16 , Sanjay K Matoo  17 , Chinnaiyan Ponnuraja  2 , Jyoti Jaju  18 , Chandrasekaran Padmapriyadarsini  2
Affiliations
Randomized Controlled Trial

Long term outcomes in drug resistant tuberculosis with Bedaquiline, Pretomanid and varying doses of Linezolid

Bella Devaleenal Daniel et al. J Infect. 2025 Jul.

Abstract

Objectives: Assess the effectiveness of bedaquiline, pretomanid and linezolid (BPaL) regimens with varying doses and duration of linezolid at the end of 48 weeks post treatment among drug resistant tuberculosis (DR TB) patients.

Methods: Multicentric pragmatic randomized clinical trial in which BPaL regimens were given for 26 weeks for pulmonary pre extensively drug resistant tuberculosis (PreXDR TB); bedaquiline, pretomanid and linezolid 600 mg for 26 weeks (arm1), structured dose reduction arms with linezolid dose reduction from 600 to 300 mg after nine weeks (arm2) and 13 weeks (arm3). Participants were followed up for recurrence-free cure up to 48 weeks post-treatment. Whole genome sequencing in sputum samples at baseline and recurrence differentiated relapse and reinfection.

Results: Of 403 enrolled, 378 were included for the modified intent-to-treat analysis based on baseline sputum culture positivity and sensitivity to medications in the study regimen. Among them, 331(88%) had recurrence-free cure at the end of 48 weeks of post-treatment follow-up; arm1:112(87%), arm2:110(88%), arm3:109(88%). Overall, 14 (12 bacteriological and 2 clinical) recurrences (arm1-four, 2-six and 3-four) occurred; 11 recurrences occurred within 24 weeks after treatment completion; four out of 11 within the first 12 weeks. Of the 10 paired sputum samples available at baseline and recurrence for comparison of lineages, there were two reinfections and eight relapses.

Conclusion: Structured dose reduction arms had comparable recurrence free cure rates as linezolid 600 mg arm when given along with bedaquiline and pretomanid for 26 weeks in PreXDR TB. Most of the recurrences occurred within the first six months.

Keywords: Bedaquiline; Dose reduction; Drug resistant tuberculosis; India; Linezolid; Pretomanid; Recurrence; Treatment outcome.

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Fig. 1
Consort of mBPaL study participants.
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