Efficacy and tolerability of linezolid as an adjunctive treatment for nontuberculous mycobacterial infections in patients with adult-onset immunodeficiency syndrome: a prospective cohort study

Background: Patients with nontuberculous mycobacterial (NTM) diseases associated with anti-interferon gamma autoantibodies (anti-IFN-γ auto-Abs) often experience recurrences, despite prolonged treatment, which requires intravenous anti-mycobacterial therapy. Linezolid (LZD) shows a potential as an adjunct treatment, but there is limited data on its long-term efficacy and safety. Methods: We conducted a prospective study from December 2017 to April 2022, to evaluate the efficacy of a nine-month oral LZD regimen in reducing NTM treatment failure, defined as relapse and the need for intravenous anti-mycobacterial therapy for suspected uncontrolled NTM or death as well as to determine its tolerability. Results: Among 40 adults (≥18 years) with NTM diseases and anti-IFN-γ auto-Abs treated with linezolid, 10 (25%) discontinued treatment early due to adverse events (AEs), including one death from suspected uncontrolled diseases at month seven. Of the 30 patients who completed the nine-month course, only five maintained their initial dose. The remaining 25 required dose modification: four temporarily paused treatment due to AEs, nine reduced to a half dose due to AEs, and 12 reduced their dose because of stable disease. By month nine, the cumulative incidence rates of relapse and treatment failure were 22.5 and 15.0%, respectively; consequently, 77.5% and 85.0% of patients remained free from the relapse and treatment failure. Overall, 24 patients (60%) reported a total of 31 AEs, with anemia and peripheral neuropathy being the most frequent. Conclusion: Our findings suggest that linezolid could be a valuable adjunct treatment for nontuberculous mycobacteria diseases in patients with anti-interferon gamma autoantibodies. However, close monitoring for adverse events is essential.