Xipei Wang1, Yifan Wang2,3, Fen Yao2,3, Shenglong Chen2, Yating Hou4, Zhijie Zheng1, Jinbiao Luo5, Binghui Qiu6, Zhanfu Li7, Yirong Wang2, Zheng Wu2, Jinhua Lan2, Chunbo Chen8,9. 1. Department of Medical Sciences, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, 510080, People's Republic of China. 2. Department of Critical Care Medicine, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, Guangdong, People's Republic of China. 3. School of Biology and Biological Engineering, South China University of Technology, Guangzhou, Guangdong, 510080, People's Republic of China. 4. Department of Oncology, Maoming People's Hospital, Maoming, 525000, Guangdong, People's Republic of China. 5. Department of Neurosurgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, 510180, People's Republic of China. 6. Department of Neurosurgery, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, People's Republic of China. 7. Department of Intensive Care Unit, Guangdong 999 Brain Hospital, Guangzhou, 510510, Guangdong, People's Republic of China. 8. Department of Intensive Care Unit of Cardiovascular Surgery, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Laboratory of South China Structural Heart Disease, Guangzhou, 510080, Guangdong, People's Republic of China. 9. The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510000, Guangdong, People's Republic of China.
Abstract
PURPOSE: The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients. METHODS: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25-4 mg/L. RESULTS: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function. CONCLUSION: In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.
PURPOSE: The aim of this study is to use a population pharmacokinetic (PK) approach to evaluate the optimal dosing strategy for linezolid (LNZ) in critically ill patients. METHODS: This multicenter, prospective, open-label, observational study was conducted in 152 patients, and 117 of them were included in the PK model, whereas the rest were in the validation group. The percentage of therapeutic target attainment (PTTA) comprising two pharmacodynamic indices and one toxicity index was used to evaluate dosing regimens based on Monte Carlo simulations stratified by low, normal, and high renal clearance for MICs of 0.25-4 mg/L. RESULTS: A single-compartment model with a covariate creatinine clearance (CrCL) was chosen as the final model. The PK parameter estimates were clearance of 5.60 L/h, with CrCL adjustment factor of 0.386, and a distribution volume of 43.4 L. For MIC ≤2 mg/L, the standard dosing regimen (600 mg q12h) for patients with severe renal impairment (CrCL, 40 mL/min) and standard dosing or 900 mg q12h for patients with normal renal functions (CrCL, 80 mL/min) could achieve PTTA ≥74%. The dose of 2400 mg per 24-h continuous infusion was ideal for augmented renal clearance (ARC) with MIC ≤1 mg/L. For MICs >2 mg/L, rare optimal dose regimens were found regardless of renal function. CONCLUSION: In critically ill patients, the standard dose of 600 mg q12h was sufficient for MIC ≤2 mg/L in patients without ARC. Moreover, a 2400 mg/day 24-h continuous infusion was recommended for ARC patients.
Authors: Max Taubert; Michael Zoller; Barbara Maier; Sebastian Frechen; Christina Scharf; Lesca-Miriam Holdt; Lorenz Frey; Michael Vogeser; Uwe Fuhr; Johannes Zander Journal: Antimicrob Agents Chemother Date: 2016-08-22 Impact factor: 5.191
Authors: Max Taubert; Johannes Zander; Sebastian Frechen; Christina Scharf; Lorenz Frey; Michael Vogeser; Uwe Fuhr; Michael Zoller Journal: J Antimicrob Chemother Date: 2017-08-01 Impact factor: 5.790