Haiyan Dong1, Jiao Xie1, Lihong Chen2, Taotao Wang1, Jinyue Sun1, Yingren Zhao3, Yalin Dong4. 1. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. 2. Central Intensive Care Unit, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, 710061, China. 3. Department of Infectious Diseases, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: zhaoyingren@sohu.com. 4. Department of Pharmacy, The First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: dongyalin@mail.xjtu.edu.cn.
Abstract
OBJECTIVES: This study evaluated the efficacy of the pharmacokinetic/pharmacodynamic (PK/PD) index for increasing the success rate of linezolid treatment based on Monte Carlo simulation, and compared differences between the calculated PK/PD breakpoints and those defined by committee for critically ill patients with linezolid treatment. METHODS: A Monte Carlo simulation involving 10000 subjects was used to analyze the pharmacokinetic parameters and microbiological data of linezolid for an effectiveness evaluation at the corresponding AUC24/MIC values (area under the serum concentration-time curve over 24h/minimum inhibitory concentration). RESULTS: As the PK/PD index of linezolid increased from 80 to 120, the corresponding probability of target attainment (PTA) decreased from 99.91% to 18.97%, with a MIC of 2mg/l. Furthermore, the cumulative fraction of response (CFR) reached <90% for several pathogens at an AUC24/MIC of 100-120, revealing a relatively lower efficacy with recommended linezolid dosing. CONCLUSIONS: These findings reveal that the target AUC24/MIC value of 80-120 requires further classification for more accurate assessment of the linezolid dose regimen. At a MIC of ≥2mg/l, the clinical outcome varies greatly for different AUC24/MIC values when applying the same dose of linezolid. In such cases, we suggest optimized adjustment of the linezolid dosage regimen.
OBJECTIVES: This study evaluated the efficacy of the pharmacokinetic/pharmacodynamic (PK/PD) index for increasing the success rate of linezolid treatment based on Monte Carlo simulation, and compared differences between the calculated PK/PD breakpoints and those defined by committee for critically illpatients with linezolid treatment. METHODS: A Monte Carlo simulation involving 10000 subjects was used to analyze the pharmacokinetic parameters and microbiological data of linezolid for an effectiveness evaluation at the corresponding AUC24/MIC values (area under the serum concentration-time curve over 24h/minimum inhibitory concentration). RESULTS: As the PK/PD index of linezolid increased from 80 to 120, the corresponding probability of target attainment (PTA) decreased from 99.91% to 18.97%, with a MIC of 2mg/l. Furthermore, the cumulative fraction of response (CFR) reached <90% for several pathogens at an AUC24/MIC of 100-120, revealing a relatively lower efficacy with recommended linezolid dosing. CONCLUSIONS: These findings reveal that the target AUC24/MIC value of 80-120 requires further classification for more accurate assessment of the linezolid dose regimen. At a MIC of ≥2mg/l, the clinical outcome varies greatly for different AUC24/MIC values when applying the same dose of linezolid. In such cases, we suggest optimized adjustment of the linezolid dosage regimen.
Authors: Rasha M El-Gaml; Noha M El-Khodary; Rania R Abozahra; Ayman A El-Tayar; Soha M El-Masry Journal: Eur J Clin Pharmacol Date: 2022-05-25 Impact factor: 3.064