title: Does contemporary vancomycin dosing achieve therapeutic targets in a heterogeneous clinical cohort of critically ill patients? Data from the multinational DALI study.
abstract: BACKGROUND
  The objective of this study was to describe the pharmacokinetics of vancomycin in ICU patients and to examine whether contemporary antibiotic dosing results in concentrations that have been associated with favourable response.
  
  
  METHODS
  The Defining Antibiotic Levels in Intensive Care (DALI) study was a prospective, multicentre pharmacokinetic point-prevalence study. Antibiotic dosing was as per the treating clinician either by intermittent bolus or continuous infusion. Target trough concentration was defined as ≥15 mg/L and target pharmacodynamic index was defined as an area under the concentration-time curve over a 24-hour period divided by the minimum inhibitory concentration of the suspected bacteria (AUC0-24/MIC ratio) >400 (assuming MIC ≤1 mg/L).
  
  
  RESULTS
  Data of 42 patients from 26 ICUs were eligible for analysis. A total of 24 patients received vancomycin by continuous infusion (57%). Daily dosage of vancomycin was 27 mg/kg (interquartile range (IQR) 18 to 32), and not different between patients receiving intermittent or continuous infusion. Trough concentrations were highly variable (median 27, IQR 8 to 23 mg/L). Target trough concentrations were achieved in 57% of patients, but more frequently in patients receiving continuous infusion (71% versus 39%; P = 0.038). Also the target AUC0-24/MIC ratio was reached more frequently in patients receiving continuous infusion (88% versus 50%; P = 0.008). Multivariable logistic regression analysis with adjustment by the propensity score could not confirm continuous infusion as an independent predictor of an AUC0-24/MIC >400 (odds ratio (OR) 1.65, 95% confidence interval (CI) 0.2 to 12.0) or a Cmin ≥15 mg/L (OR 1.8, 95% CI 0.4 to 8.5).
  
  
  CONCLUSIONS
  This study demonstrated large interindividual variability in vancomycin pharmacokinetic and pharmacodynamic target attainment in ICU patients. These data suggests that a re-evaluation of current vancomycin dosing recommendations in critically ill patients is needed to more rapidly and consistently achieve sufficient vancomycin exposure.
authors.forename: Stijn
authors.initials: S
authors.lastname: Blot
authors.forename: Despoina
authors.initials: D
authors.lastname: Koulenti
authors.forename: Murat
authors.initials: M
authors.lastname: Akova
authors.forename: Matteo
authors.initials: M
authors.lastname: Bassetti
authors.forename: Jan J
authors.initials: JJ
authors.lastname: De Waele
authors.forename: George
authors.initials: G
authors.lastname: Dimopoulos
authors.forename: Kirsi-Maija
authors.initials: KM
authors.lastname: Kaukonen
authors.forename: Claude
authors.initials: C
authors.lastname: Martin
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
authors.forename: Jordi
authors.initials: J
authors.lastname: Rello
authors.forename: Andrew
authors.initials: A
authors.lastname: Rhodes
authors.forename: Therese
authors.initials: T
authors.lastname: Starr
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood*; D015331:Cohort Studies; D016638:Critical Illness / Q000453:epidemiology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014640:Vancomycin / Q000008:administration & dosage* / Q000097:blood*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin