Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis

Background
The optimal dosing strategy of linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis remains unclear. We conducted an individual patient data meta-analysis to determine the optimal linezolid dosing strategy.

Methods
We searched for randomised controlled trials and prospective cohort studies on short-course all‑oral regimens containing linezolid for treating multidrug-resistant and rifampicin-resistant tuberculosis in PubMed, Embase and Scopus up to 31 August 2023. Patients were grouped according to linezolid dosing patterns. Time to treatment success and adverse events of grade 3 and higher were analysed using the Fine–Gray sub-distribution hazard model.

Results
Of 12 eligible studies, eight (four randomised controlled trials, four prospective studies) were included. Overall, 945 patients were grouped as follows: group 1 (600 mg·day−1 linezolid for 8 weeks), group 2 (600 mg·day−1 for 16 weeks, then 300 mg·day−1 for 8 weeks), group 3 (600 mg·day−1 for 39 weeks) and group 4 (1200 mg·day−1 for 25 weeks). Proportions of patients achieving treatment success were 59.1%, 90.4%, 91.3% and 96.0%, respectively. Compared with group 2, group 1 (adjusted sub-distribution hazard ratio (SHR) 0.24, 95% CI 0.08–0.71) and group 3 (adjusted SHR 0.36, 95% CI 0.16–0.81) had lower success rates. While group 4 showed no significant difference in treatment success versus group 2 (adjusted SHR 0.57, 95% CI 0.23–1.43), it had a higher rate of adverse events of grade 3 and higher (adjusted SHR 2.29, 95% CI 1.37–3.83).

Conclusion
A dosing strategy of 600 mg·day−1 linezolid for 16 weeks then 300 mg·day−1 for 8 weeks could be optimal for treating multidrug-resistant and rifampicin-resistant tuberculosis when considering effectiveness and safety.