Risk factors associated with high linezolid trough plasma concentrations

The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin.

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 Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed.

34.6% patients had a Cmin >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 Cmin. The only factor independently associated with Cmin >8 was the renal function. Patients with an eGF < 40 mL/min had significantly higher Cmin than those with eGF > 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109).

High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.