N-acetylcysteine reduces incidence and duration of linezolid-associated thrombocytopenia in critically ill patients: A randomized controlled trial.

Linezolid-associated thrombocytopenia (LAT) limits its use in critically ill patients. This double-blind, randomized, placebo-controlled trial evaluated intravenous N-acetylcysteine (IV NAC) for LAT prevention in 250 critically ill adults receiving linezolid for ≥ 48 h. Patients received IV NAC (600 mg every 12 h) or placebo. The primary endpoint was LAT incidence (platelet count <150 × 10 ³/mm³ or >50 % reduction from baseline). NAC significantly reduced LAT incidence (16.8 % vs. 41.6 %; p < 0.001), platelet transfusions (1.6 % vs. 11.2 %; p = 0.003), and linezolid discontinuations (6.4 % vs. 32.0 %; p < 0.001). NAC delayed LAT onset (adjusted hazard ratio 0.24; p < 0.001) and accelerated platelet recovery (adjusted hazard ratio 3.88; p = 0.011), with greatest benefit in moderate-severity cases. These findings suggest IV NAC may offer a preventive benefit against LAT in critically ill patients, though multicenter validation is needed to confirm generalizability across diverse clinical settings. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT05944458. Registered on July 6, 2023.