title: Impact of vancomycin protein binding on target attainment in critically ill children: back to the drawing board?
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.|Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.|Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.
authors.forename: Pieter A J G
authors.initials: PA
authors.lastname: De Cock
authors.affiliation: Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.|Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Desmet
authors.affiliation: Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.
authors.forename: Annick
authors.initials: A
authors.lastname: De Jaeger
authors.affiliation: Department of Paediatric Intensive Care, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
authors.forename: Dominique
authors.initials: D
authors.lastname: Biarent
authors.affiliation: Department of Paediatric Intensive Care, Ghent University Hospital, Ghent, Belgium.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Dhont
authors.affiliation: Department of Cardiac Intensive Care, Ghent University Hospital, Ghent, Belgium.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Herck
authors.affiliation: Department of Paediatric Intensive Care, Hôpital Universitaire des Enfants Reine Fabiola, Brussels, Belgium.
authors.forename: Daphné
authors.initials: D
authors.lastname: Vens
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Colman
authors.affiliation: Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Veronique
authors.initials: V
authors.lastname: Stove
authors.affiliation: Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Commeyne
authors.affiliation: Department of Paediatric Nephrology, Ghent University Hospital, Ghent, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Vande Walle
authors.affiliation: Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.|Department of Emergency Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: De Paepe
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001798:Blood Proteins / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007362:Intensive Care Units; D016014:Linear Models; D008297:Male; D008826:Microbial Sensitivity Tests; D011446:Prospective Studies; D011485:Protein Binding; D014640:Vancomycin / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001798:Blood Proteins; D014640:Vancomycin