Durable three-year outcomes and persistent neuropathy following nine-month all-oral regimens for rifampicin-resistant tuberculosis: a multicentre cohort study in China

Overview

Rifampicin-resistant tuberculosis remains a significant clinical and public health challenge. Nine-month all-oral regimens incorporating bedaquiline and linezolid have demonstrated high efficacy in short-term follow-up, but limited evidence exists regarding treatment durability beyond 24 months and long-term linezolid-related neurotoxicity. This multicentre cohort study evaluated three-year outcomes and persistent adverse effects following completion of nine-month all-oral therapy in patients with MDR/RR-TB or pre-XDR-TB.

Methods and approach

The study enrolled 124 adults with culture-confirmed MDR/RR-TB or pre-XDR-TB between May 2020 and July 2022 across multiple centres in China. Participants received one of four nine-month all-oral regimens containing linezolid at 600 mg daily, all incorporating bedaquiline. The primary efficacy outcome was defined as favourable outcome, operationalized as the absence of treatment failure, relapse, or death at 36 months post-treatment completion. Safety assessment focused on clinician-confirmed persistent linezolid-related neuropathic or visual symptoms sustained for at least 24 months. Comparative analysis of the four regimens employed log-rank testing.

Key Findings

At 36 months after treatment completion, 111 of 124 participants achieved a favourable outcome, representing 89.5% (95% CI 82.9–93.8). No statistically significant differences in favourable outcomes were observed between the four treatment regimens. Persistent linezolid-related adverse symptoms were documented in 28 of 124 patients (22.6%), with foot numbness as the most prevalent symptom, affecting 22 patients (17.7%). These persistent symptoms met criteria of clinician confirmation and persistence exceeding 24 months.

Implications

The findings demonstrate that nine-month all-oral regimens for RR-TB produce durable therapeutic responses sustained through three-year follow-up, supporting the clinical utility of abbreviated treatment courses in this population. However, the considerable prevalence of persistent linezolid-related peripheral neuropathy remains a significant safety concern requiring systematic clinical attention. Strategies to mitigate long-term linezolid neurotoxicity warrant investigation, including cumulative dose optimization, therapeutic drug monitoring approaches, and evaluation of linezolid-sparing alternative regimens where clinically appropriate.