A71-13 Linezolid-Associated Adverse Events in Bedaquiline- And Pretomanid-Containing Regimens for Rifampicin-Resistant Tuberculosis in Indonesia

Rationale

The BPaL/M regimen has demonstrated effectiveness in treating rifampicin-resistant tuberculosis (RR-TB) compared with longer-duration treatments. However, linezolid-associated toxicity remains a major concern. We aimed to investigate linezolid-associated adverse events (AEs) in the real-world use of the BPaL/M regimen in Indonesia.

Methods

This was a single-centre retrospective study utilizing the Sistem Informasi Tuberkulosis (SITB, Indonesia), a national tuberculosis registry. We included pulmonary RR-TB individuals aged ≥14 years who were treated with the BPaL/M regimen at Persahabatan Hospital, the national respiratory referral center in Indonesia, between January 2023 and December 2025 with documented treatment outcomes. Adverse events were self-reported by individuals or evaluated by physicians and recorded in the registry. Adverse events assessed included myelosuppression, hepatotoxicity, optic neuritis, peripheral neuropathy, and prolonged QT. Adverse events were recorded as present or absent regardless of severity. The severity of myelosuppression, hepatotoxicity, and QT prolongation was graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 6. Bivariate analyses and multivariable logistic regression were performed using SPSS version 20.

Results

We included 195 individuals, of whom 146 (74.9%) experienced linezolid-related AEs. Most AEs were mild and did not require dose adjustment. Four (2.1%) and two (1.0%) individuals experienced grade 3-4 myelosuppression and hepatotoxicity, respectively. Peripheral neuropathy was associated with favourable treatment outcomes (OR 3.8, 95% CI 1.8-7.8; p < 0.01) and was more frequently observed among individuals with MDR-TB compared with Pre-XDR-TB (58.4% vs 29.4%; OR 0.30, 95% CI 0.10-0.88; p = 0.021). Linezolid dose adjustment occurred in only six individuals (3.1%). Among those with dose adjustment, 50% achieved favourable outcomes compared with 80% in individuals without dose adjustment (p = 0.013). Overall, the presence of any linezolid-related AEs, regardless of severity, was associated with favourable treatment outcomes (OR 3.9, 95% CI 1.9-8.0; p < 0.001). This association remained statistically significant in multivariable analysis adjusted for age, sex, diabetes, treatment regimen (BPaL vs BPaLM), and previous TB treatment history (OR 3.9, 95% CI 1.9-8.3; p < 0.001). Linezolid dose adjustment and HIV status were not included in the multivariable model due to low event frequency.

Conclusion

Linezolid-associated AEs were common among individuals treated with the BPaL/M regimens, however, most were of low severity and did not require dose modification. The association between reported AEs and favourable treatment outcomes suggests potential treatment adherence or exposure-related effects. Larger studies are needed to further elucidate the clinical implications of linezolid-related toxicity in BPaL/M regimens.

This abstract is funded by: None