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 (MDR/RR-TB) remains unclear. We conducted an individual patient data (IPD) meta-analysis to determine the optimal linezolid dosing strategy.

METHODS

We searched PubMed, Embase, and Scopus for randomised controlled trials (RCTs) and prospective cohort studies on short-course, all-oral regimens containing linezolid for treating MDR/RR-TB through 31 August 2023. Patients were grouped according to linezolid dosing patterns. Time to treatment success and adverse events≥grade 3 were analysed using the Fine-Gray sub-distribution hazard model.

RESULTS

Of 12 eligible studies, 8 (4 RCTs, 4 prospective) were included. Overall, 945 patients were grouped as follows: group 1 (600 mg linezolid for 8 weeks), group 2 (600 mg for 16 weeks, then 300 mg for 8 weeks), group 3 (600 mg for 39 weeks), and group 4 (1200 mg for 25 weeks). Proportions of patients achieving treatment success were 59·1%, 90·4%, 91·3%, and 96·0%, respectively. Compared with group 2, groups 1 (adjusted sub-distribution hazard ratio [aSHR], 0·24, 95% confidence interval [CI], 0·08-0·71) and 3 (aSHR, 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 (aSHR, 0·57, 95% CI, 0·23-1·43), it had a higher rate of adverse events≥grade 3 (aSHR, 2·29, 95% CI, 1·37-3·83).

CONCLUSION

A dosing strategy of 600 mg linezolid daily for 16 weeks, then 300 mg for 8 weeks, could be optimal for treating MDR/RR-TB when considering effectiveness and safety.