Risk factors associated with high linezolid trough plasma concentrations

Aim: The major concern of linezolid is the adverse events. High linezolid trough serum concentration (C-min) has been associated with toxicity. The aim of this study was to analyze factors associated with high C-min. Methods: Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High C-min was considered when it was >8 mg/L. Univariate and multivariate analysis were performed. Results: 34.6% patients had a C-min >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD <40 mL/min. There were more patients co-treated with rifampin in the group with low C-min. The only factor independently associated with C-min >8 was the renal function. Patients with an eGF <40 mL/min had significantly higher C-min than those with eGF >80 mL/min (OR: 4.273) and there was a trend towards a high C-min in patients with eGF between 40-80 mL/min (OR: 2.109). Conclusions: High C-min were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.