Researchers conducted an individual patient data meta-analysis to determine the optimal dosing strategy for linezolid in patients with MDR/RR-TB.

A literature search was performed for trials of short-course, all-oral regimens containing linezolid to treat patients with MDR/RR-TB in the PubMed, Embase, and Scopus databases. Eligible studies were randomized controlled trials (RCTs) and prospective cohort studies that included short-course, all-oral regimens containing linezolid for the treatment of MDR/RR-TB or extensively drug-resistant TB published through August 31, 2023.

Revised World Health Organization definitions were used for treatment outcomes. Treatment success was defined as cases classified as cured and those in which treatment was completed.

The analysis included anonymized data from 8 studies (4 RCTs and 4 prospective cohort studies), with 945 patients (median age, 35 years; 63% male) included in the final analysis. Group 1 (215 patients) comprised those who received 600 mg of linezolid daily for 8 weeks. Group 2 (447 patients) received 600 mg of linezolid for 16 weeks, followed by 300 mg of linezolid for 8 weeks. Group 3 (183 patients) received 600 mg of linezolid maintained for a median of 39 weeks. Group 4 (100 patients) comprised those who had 1200 mg of linezolid for 25 weeks.

Overall, 794 (84.0%) patients achieved treatment success. Group 1 had the lowest proportion of success (59.1%), and groups 2, 3, and 4 had rates of 90.4%, 91.3%, and 96.0%, respectively. Group 1 also had the highest rate of treatment failure, death, and loss to follow-up. Treatment failure occurred in 34 participants (15.8%) in group 1, compared with 13 patients in groups 2 to 4 combined.

The patient’s age (in years) had a negative association with treatment success (adjusted subdistribution hazard ratio [aSHR], 0.98; 95% CI, 0.97-0.99), and body mass index (aSHR, 1.03; 95% CI, 1.01-1.06) was positively associated with treatment success in the adjusted analysis.

Compared with group 2 (the reference group), significantly decreased rates of treatment success were seen in group 1 (aSHR, 0.24; 95% CI, 0.08-0.71) and group 3 (aSHR, 0.36; 95% CI, 0.16-0.81). Treatment success in group 4 (aSHR, 0.57; 95% CI, 0.23-1.43) was not significantly different vs group 2.

Adverse events grades 3 and higher occurred in 235 patients (24.9%), with the highest proportion in group 4 (43.0%) and the lowest in group 3 (13.7%). Group 1 had an increased rate of adverse events (aSHR, 1.84; 95% CI, 0.75-4.50), and group 3 had a reduced rate (aSHR, 0.55; 95% CI, 0.18-1.67), compared with group 2. However, the differences were not statistically significant. Group 4 had a significantly increased rate of adverse events vs group 2 (aSHR, 2.29; 95% CI, 1.37-3.83).

In citing study limitations, the investigators noted they were unable to confirm whether tapering linezolid at another timepoint would result in similar effects to maintaining the 600-mg dose. Also, no adjustments were made for use of companion drugs or for drug resistance pattern, alcohol abuse, diabetes, and HIV infection.

“Initially, a front-loaded 600 mg dose of linezolid enhances bactericidal activity during the early stages of treatment. Subsequently, reducing the dose to 300 mg maintains the sterilising effect while minimising the risk of adverse events,” the study authors stated.

By Colby Stong

References:

Kwak N, Kim J-Y, Han A, et al. Optimal dosing and duration of linezolid for the treatment of multidrug-resistant and rifampicin-resistant tuberculosis: an individual patient data meta-analysis. Eur Respir J. Published online July 17, 2025. doi:10.1183/13993003.00315-2025

Source: Infectious Disease Advisor