BACKGROUND AND OBJECTIVES: Severe sepsis is a major problem as cause of high rates morbidity and mortality in intensive care units (ICU). Aminoglycosides are an important group of antimicrobials used for severe sepsis. However, aminoglycoside pharmacokinetics in ICU patients may be altered during sepsis, which can affect the drug concentrations. Therefore, this study was undertaken to examine the relationship between amikacin disposition kinetics after a 25 mg/kg loading dose and hemodynamic response to sepsis, as well as clinical parameters, in a population of critically ill patients. METHODS: In this work, 30 patients who were candidate to amikacin therapy following Gram negative sepsis were enrolled. The pharmacokinetic profile of amikacin by a non-compartmental model was calculated for each patient. RESULTS: Mean volume of distribution was 0.36 ± 0.07 L/kg and mean serum amikacin clearance was 3.88 ± 0.97 ml/min/kg. In the case of Vd, APACHE II score correlation was significant. In the case of amikacin clearance, two covariates including creatinine clearance and Sr Cr significant correlation was found. CONCLUSIONS: It appears necessary to use higher amikacin dosage (≥ 25 mg/kg) considering hemodynamic response of patients to sepsis. To achieve therapeutic drug concentration a close drug monitoring and a shift from the population mean toward a value more representative of the critically ill patient subpopulation is crucial.
BACKGROUND AND OBJECTIVES: Severe sepsis is a major problem as cause of high rates morbidity and mortality in intensive care units (ICU). Aminoglycosides are an important group of antimicrobials used for severe sepsis. However, aminoglycoside pharmacokinetics in ICU patients may be altered during sepsis, which can affect the drug concentrations. Therefore, this study was undertaken to examine the relationship between amikacin disposition kinetics after a 25 mg/kg loading dose and hemodynamic response to sepsis, as well as clinical parameters, in a population of critically illpatients. METHODS: In this work, 30 patients who were candidate to amikacin therapy following Gram negative sepsis were enrolled. The pharmacokinetic profile of amikacin by a non-compartmental model was calculated for each patient. RESULTS: Mean volume of distribution was 0.36 ± 0.07 L/kg and mean serum amikacin clearance was 3.88 ± 0.97 ml/min/kg. In the case of Vd, APACHE II score correlation was significant. In the case of amikacin clearance, two covariates including creatinine clearance and Sr Cr significant correlation was found. CONCLUSIONS: It appears necessary to use higher amikacin dosage (≥ 25 mg/kg) considering hemodynamic response of patients to sepsis. To achieve therapeutic drug concentration a close drug monitoring and a shift from the population mean toward a value more representative of the critically illpatient subpopulation is crucial.
Authors: C Burdet; O Pajot; C Couffignal; L Armand-Lefèvre; A Foucrier; C Laouénan; M Wolff; L Massias; F Mentré Journal: Eur J Clin Pharmacol Date: 2014-10-21 Impact factor: 2.953
Authors: Derek N Bremmer; Cornelius J Clancy; Ellen G Press; Reem Almaghrabi; Liang Chen; Yohei Doi; M Hong Nguyen; Ryan K Shields Journal: Antimicrob Agents Chemother Date: 2014-10-06 Impact factor: 5.191
Authors: Fekade Bruck Sime; Adam Johnson; Sarah Whalley; Anahi Santoyo-Castelazo; A Bruce Montgomery; Kathie Ann Walters; Jeffrey Lipman; William W Hope; Jason A Roberts Journal: Antimicrob Agents Chemother Date: 2016-12-27 Impact factor: 5.191