Compared with the standard dose, low-dose linezolid was found to be associated with improved outcomes, increased tolerability to longer treatment durations, and fewer adverse events (AEs) in patients with multidrug-resistant (MDR) tuberculosis (TB) infection, according to study findings published in Open Forum Infectious Diseases.
Researchers in California conducted a real-world data analysis to assess the efficacy of low-dose linezolid among patients with MDR-TB infection between January 2009 and December 2016. The primary endpoints were treatment duration, treatment success, and AE occurrence. Chi-square, Fischer Exact, and Wilcoxon Rank-sum testing were used to evaluate significant differences in demographics and treatment outcomes between patients who continued linezolid at the standard dose vs those who switched to lower doses.
Among 194 patients with MDR-TB infection considered for enrollment, 69 (36%) were included in the final analysis and initiated linezolid treatment at the daily recommended dose of 600 mg. Of these patients, 57% continued treatment at this dose, and 43% were switched to either a daily dose of 300 mg (29%) or intermittent dosing (14%).
The mean duration of treatment was decreased among patients continued with standard dose linezolid vs those who switched to low-dose linezolid (240 vs 535 days; P <.0001). Only 1 (1.5%) patient discontinued treatment due to AE occurrence, 2 (2.9%) were lost to follow-up, and 2 (2.9%) died before the end of the study. The remaining 63 (91%) patients achieved treatment success, with higher rates of success observed among those in the low-dose group (P =.03).
Among all patients, 71% reported at least 1 hematologic-related AE and 65% reported at least 1 neurologic-related AE. The researchers found that the rate of AEs per 1 month of treatment in patients who switched to low-dose linezolid was significantly increased for the period prior to vs after switching to a lower dose (0.32 vs 0.10; P =.03).
Study limitations include the retrospective design, the small sample size, and insufficient post-treatment follow-up data.
“[O]ur results can inform clinical decision-making for MDR TB patients who have linezolid-related toxicity,” the researchers concluded.
Mase A, Lowenthal P, True L, Henry L, Barry P, Flood J. Low dose linezolid for treatment of patients with multidrug-resistant (MDR) tuberculosis (TB). Open Forum Infect Dis. Published online October 5, 2022. doi:10.1093/ofid/ofac500