Linezolid-associated neurologic toxicity in patients with drug-resistant tuberculosis in a bedaquiline-based regimen: A scoping review

Abstract

Bedaquiline and linezolid have shown a high efficacy in treating drug-resistant tuberculosis (DR-TB). Neurologic toxicity is the primary adverse effect of linezolid, leading to dose reduction or early discontinuation. We comprehensively reviewed the incidence of neurologic toxicity, including peripheral and optic neuropathy associated with linezolid in patients with DR-TB in bedaquiline-based regimens. We conducted a scoping review under the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline for a scoping review. We retrieved ten cohort studies that met the inclusion criteria. Of 3640 DR-TB patients in the included studies, 653 (17.9%) were HIV. 1154/3640 (31.7%) patients experienced neurologic toxicity, and among them, 982 (85.0%), 162 (14.0%), and 10 (1.0%) had peripheral neuropathy, optic neuritis, and both, respectively. Peripheral and optic neuropathy occurred at a median time from 18 weeks and 23 weeks, respectively, after the first initiation of linezolid. Linezolid interruption, including dose adjustment and temporary discontinuation, ranged from 13.8% to 34.9%. None of the studies reported that HIV was associated with neuropathy. However, it was significantly associated with linezolid interruption. The incidence of peripheral and optic neuropathy occurred more in DR-TB patients with trough linezolid concentration ≥2 mg/L. However, trough linezolid concentration ≥2 mg/L was not associated with peripheral and optic neuropathy. The incidence of neurologic toxicity was relatively high in DR-TB patients with a regimen containing linezolid. Peripheral neuropathy was the most prevalent neurologic toxicity during the treatment of linezolid. It considers conducting therapeutic drug monitoring of linezolid to improve patient safety.