Adverse effects of linezolid in the treatment of drug-resistant tuberculosis: a scoping review.

Background: Linezolid (LZD) has emerged as a key drug for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) treatment. However, its clinical use is limited by substantial toxicity. This scoping review aimed to synthesise evidence on LZD-associated adverse effects (AEs) to support safer and more effective TB management clinical decisions. Methods: A systematic search of PubMed, Scopus, Web of Science, and EMBASE databases (conducted in October 2024) identified 103 primary studies published between 2005 and 2024 that reported AEs related to LZD use in MDR/XDR-TB. Data on frequency, severity, onset, and management of AEs were extracted and narratively synthesised. Results: Of the 103 included studies, 102 (99%) reported at least one AE. The overall frequency of AEs ranged from 2.8% to 100%. Neurological toxicity was reported in 3.5-91.9% of patients, most commonly presenting as peripheral neuropathy. Haematological toxicity was observed in 1.9-84.6% of participants, mainly reported as anaemia and thrombocytopenia. Gastrointestinal disturbances, metabolic complications, such as lactic acidosis and hyperlactacidaemia, and dermatological events were also reported. Conclusion: LZD-associated toxicity is frequent and often clinically significant, particularly during prolonged treatment. Careful patient assessment, including comorbidities and potential contributing factors such as vitamin deficiencies, along with regular monitoring and, where available, therapeutic drug monitoring, may help optimise safety and treatment outcomes. Future research should focus on standardised toxicity assessment, pharmacokinetic-based dosing strategies, and the inclusion of diverse patient populations to improve the safety and effectiveness of LZD-based regimens.