title: Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study.
abstract: OBJECTIVE
  In critically ill patients receiving continuous renal replacement therapy, we aimed to assess the variability of antibiotic trough concentrations, the influence of effluent flow rates on such concentrations, and the incidence of suboptimal antibiotic dosage.
  
  
  METHODS
  Prospective, observational, multicenter, pharmacokinetic study.
  
  
  METHODS
  Four tertiary intensive care units within the multicenter RENAL randomized controlled trial of continuous renal replacement therapy intensity.
  
  
  METHODS
  Twenty-four critically ill adult patients with acute kidney injury receiving ciprofloxacin, meropenem, piperacillin/tazobactam, or vancomycin during continuous renal replacement therapy.
  
  
  METHODS
  We obtained trough blood samples and measured antibiotic concentrations.
  
  
  RESULTS
  We obtained data from 40 dosing intervals and observed wide variability in trough concentrations (6.7-fold for meropenem, 3.8-fold for piperacillin, 10.5-fold for tazobactam, 1.9-fold for vancomycin, and 3.9-fold for ciprofloxacin). The median (interquartile range) trough concentrations (mg/L) for meropenem was 12.1 (7.8-18.4), 105.0 (74.4-204.0)/3.8 (3.4-21.8) for piperacillin/tazobactam, 12.0 (9.8-16.0) for vancomycin, and 3.7 (3.0-5.6) for ciprofloxacin. Overall, 15% of dosing intervals did not meet predetermined minimum therapeutic target concentrations, 40% did not achieve the higher target concentration, and, during 10% of dosing intervals, antibiotic concentrations were excessive. No difference, however, was found between patients on the basis of the intensity of continuous renal replacement therapy; this effect may have been obscured by differences in dosing regimens, time off the filter, or altered pharmacokinetics.
  
  
  CONCLUSIONS
  There is significant variability in antibiotic trough concentrations in critically ill patients receiving continuous renal replacement therapy, which did not only appear to be influenced by effluent flow rate. Here, empirical dosing of antibiotics failed to achieve the target trough antibiotic concentration during 25% of the dosing intervals.
authors.affiliation: Burns, Trauma, and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia. 1darren1@gmail.com
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Priya
authors.initials: P
authors.lastname: Nair
authors.forename: Louise
authors.initials: L
authors.lastname: Cole
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D058186:Acute Kidney Injury / Q000628:therapy; D000368:Aged; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002939:Ciprofloxacin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D016638:Critical Illness; D005260:Female; D006440:Hemofiltration / Q000379:methods; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D010397:Penicillanic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D010878:Piperacillin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D000078142:Tazobactam; D013845:Thienamycins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014640:Vancomycin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000900:Anti-Bacterial Agents; D013845:Thienamycins; D002939:Ciprofloxacin; D014640:Vancomycin; D010397:Penicillanic Acid; D000077731:Meropenem; D000078142:Tazobactam; D010878:Piperacillin