Occurrence and predictors of adverse events associated with linezolid in the treatment of patients with drug resistant tuberculosis and their impact on treatment outcomes

Background: WHO recommends linezolid (LZD) for Drug-Resistant Tuberculosis (DR-TB) despite its frequent adverse events, highlighting the importance of monitoring and managing adverse drug reactions (ADRs) to prevent unfavorable treatment outcomes. This study aims to assess the frequency, severity, predictors, and treatment impact of linezolid-related adverse events (AEs) in patients receiving bedaquiline-based all-oral longer regimens. Materials and methods: Data was collected retrospectively from subjects diagnosed with DR-TB on LZD containing anti-TB drugs as per Programmatic Management of DR-TB (PMDT) guidelines-2021 at Nodal DR TB Centre - Mysore from January 2018 to January 2023. Results: Among 182 subjects studied, total number of AEs recorded were 116. LZD related peripheral neuropathy accounted - 11%, optic neuritis - 10.4%, anaemia - 21.4% cases, nausea – 37.9% and vomiting - 18.7%. LZD was permanently discontinued because of AEs in 41/182 (35.3%) patients. The cumulative incidence of AEs increased rapidly during the first 6 months of treatment. These AEs resulted in LZD dose change or discontinuation in about one fourth (82/182, 45%) of all LZD treated patients. Patients with diabetes (DM) and People Living with HIV (PLHIV) associated with an increased risk of LZD related AEs. Patients with BMI < 18.5 were 1.7 times more likely to have LZD-related AEs. Conclusion: Among the all MDR-TB patients treated with LZD containing regimen, >60% experienced LZD-related AEs. Haematological AEs were most common followed by peripheral and optic neuropathy of all LZD-related AEs. Patients with comorbid conditions like DM and PLHIV were significantly associated with AEs. Being underweight can be considered a potential risk factor for LZD-related AEs.