Pieter A J G De Cock1,2,3, Sarah Desmet1,2, Annick De Jaeger3, Dominique Biarent4, Evelyn Dhont3, Ingrid Herck5, Daphné Vens4, Sofie Colman6, Veronique Stove6, Sabrina Commeyne1, Johan Vande Walle7, Peter De Paepe2,8. 1. Department of Pharmacy, Ghent University Hospital, Ghent, Belgium. 2. Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium. 3. Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium. 4. Department of Paediatric Intensive Care, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium. 5. Department of Cardiac Intensive Care, Ghent University Hospital, Ghent, Belgium. 6. Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium. 7. Department of Paediatric Nephrology, Ghent University Hospital, Ghent, Belgium. 8. Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium.
Abstract
Objectives: The objectives of this observational study were to investigate plasma protein binding and to evaluate target attainment rates of vancomycin therapy in critically ill children. Patients and methods: Paediatric ICU patients, in whom intravenous intermittent dosing (ID) or continuous dosing (CD) with vancomycin was indicated, were included. Covariates on unbound vancomycin fraction and concentration were tested using a linear mixed model analysis and attainment of currently used pharmacokinetic/pharmacodynamic (PK/PD) targets was evaluated. Clinicaltrials.gov: NCT02456974. Results: One hundred and eighty-eight plasma samples were collected from 32 patients. The unbound vancomycin fraction (median = 71.1%; IQR = 65.4%-79.7%) was highly variable within and between patients and significantly correlated with total protein and albumin concentration, which were both decreased in our population. Total trough concentration (ID) and total concentration (CD) were within the aimed target concentrations in 8% of patients. The targets of AUC/MIC ≥400 and f AUC/MIC ≥200 were achieved in 54% and 83% of patients, respectively. Unbound vancomycin concentrations were adequately predicted using the following equation: unbound vancomycin concentration (mg/L) = 5.38 + [0.71 × total vancomycin concentration (mg/L)] - [0.085 × total protein concentration (g/L)]. This final model was externally validated using 51 samples from another six patients. Conclusions: The protein binding of vancomycin in our paediatric population was lower than reported in non-critically ill adults and exhibited large variability. Higher target attainment rates were achieved when using PK/PD indices based on unbound concentrations, when compared with total concentrations. These results highlight the need for protein binding assessment in future vancomycin PK/PD research.
Objectives: The objectives of this observational study were to investigate plasma protein binding and to evaluate target attainment rates of vancomycin therapy in critically ill children. Patients and methods: Paediatric ICU patients, in whom intravenous intermittent dosing (ID) or continuous dosing (CD) with vancomycin was indicated, were included. Covariates on unbound vancomycin fraction and concentration were tested using a linear mixed model analysis and attainment of currently used pharmacokinetic/pharmacodynamic (PK/PD) targets was evaluated. Clinicaltrials.gov: NCT02456974. Results: One hundred and eighty-eight plasma samples were collected from 32 patients. The unbound vancomycin fraction (median = 71.1%; IQR = 65.4%-79.7%) was highly variable within and between patients and significantly correlated with total protein and albumin concentration, which were both decreased in our population. Total trough concentration (ID) and total concentration (CD) were within the aimed target concentrations in 8% of patients. The targets of AUC/MIC ≥400 and f AUC/MIC ≥200 were achieved in 54% and 83% of patients, respectively. Unbound vancomycin concentrations were adequately predicted using the following equation: unbound vancomycin concentration (mg/L) = 5.38 + [0.71 × total vancomycin concentration (mg/L)] - [0.085 × total protein concentration (g/L)]. This final model was externally validated using 51 samples from another six patients. Conclusions: The protein binding of vancomycin in our paediatric population was lower than reported in non-critically ill adults and exhibited large variability. Higher target attainment rates were achieved when using PK/PD indices based on unbound concentrations, when compared with total concentrations. These results highlight the need for protein binding assessment in future vancomycin PK/PD research.
Authors: Frank Kloprogge; Louise F Hill; John Booth; Nigel Klein; Adam D Irwin; Garth Dixon; Joseph F Standing Journal: Antimicrob Agents Chemother Date: 2019-04-25 Impact factor: 5.191
Authors: Bongjin Lee; Soo Jung Kim; June Dong Park; Jiun Park; Ae Hee Jung; Sun Hoi Jung; Yu Hyeon Choi; Hee Gyung Kang; Il Soo Ha; Hae Il Cheong Journal: PLoS One Date: 2018-06-21 Impact factor: 3.240
Authors: Janneke M Brussee; Elke H J Krekels; Elisa A M Calvier; Semra Palić; Amin Rostami-Hodjegan; Meindert Danhof; Jeffrey S Barrett; Saskia N de Wildt; Catherijne A J Knibbe Journal: AAPS J Date: 2019-06-27 Impact factor: 4.009