Applying pharmacokinetic/pharmacodynamic measurements for linezolid in critically ill patients: optimizing efficacy and reducing resistance occurrence

Abstract

Purpose: Linezolid (LZD) levels are frequently insufficient in intensive care unit (ICU) patients receiving standard dose, which is predictive of a poor prognosis. Alternative dosing regimens are suggested to address these insufficient levels, which are substantial factors contributing to the emergence of multidrug-resistant bacteria, resulting in increased morbidity and mortality among people who are critically ill. Methods: Forty-eight patients admitted to the intensive care unit were enrolled in an open-label, prospective, randomized study and assigned to one of three LZD administration modes: intermittent groupI (GpI) (600 mg/12 h), continuous infusion groupII (GpII) (1200 mg/24 h) or continuous infusion with loading dose groupIII (GpIII) (on Day 1, 300 mg intravenously plus 900 mg continuous infusion, followed by 1200 mg/24 h on Day 2). We evaluated serum levels of LZD using a validated ultra-performance liquid chromatography (UPLC) technique. Results: Time spent with a drug concentration more than 85% over the minimum inhibitory concentration (T > MIC) was substantially more common in GpII and III than in GpI (P < 0.01). AUC/MIC values greater than 80 were obtained more frequently with continuous infusion GpIII and GpII than with intermittent infusion GpI, at 62.5%, 37.5% and 25%, respectively (P < 0.01). In GpI, the mortality rate was significantly higher than in the other groups. Conclusion: In critically ill patients, continuous infusion with a loading dose (GpIII) is obviously superior to continuous infusion without a loading dose (GpII) or intermittent infusion (GpI) for infection therapy. Additionally, it might limit fluctuations in plasma concentrations, which may help overcome LZD resistance.