Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC 24 /MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (C min ) and to determine factors associated with a C min < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a C min determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low C min . A total of 29.5% of patients had a C min < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of C min < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P ؍ 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P ؍ 0.006). A linezolid C min of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.L inezolid belongs to a family of antimicrobials (oxazolidinones) that inhibit bacterial protein synthesis by preventing the fusion of 30S and 50S ribosomal subunits (1). During the last 10 years, linezolid has been widely used with good clinical results for the treatment of skin and soft tissue infections or nosocomial and health care-related pneumonia (2, 3). Linezolid has time-dependent activity, and the best predictors of its efficacy are the percentage of time that plasma concentrations exceed the MIC and the area under the concentrationtime curve over 24 h in the steady state divided by the MIC (AUC 24 /MIC ratio) (4). In a retrospective study of linezolid in a compassionate use program, a higher success rate was observed when concentrations remained above the MIC for the entire dosing interval and when AUC 24 /MIC values were 80 to 120 (5). Some recent data suggest that the linezolid trough plasma concentration (C min ), in some patients, is below the MIC 90 of linezolid for staphylococci (6).The aim of our study was to analyze the linezolid trough plasma concentration in a consecutive series of patients with an acute infection and to determine how often trough concentrations were Ͻ2 mg/liter (MIC 90 of linezolid for Staphylococcus aureus) and other clinically relevant thresholds (0.5, 1, and 4 mg/liter).
MATERIALS AND METHODSThe linezolid trough plasma concent...