title: A multicenter study on the effect of continuous hemodiafiltration intensity on antibiotic pharmacokinetics.
abstract: BACKGROUND
  Continuous renal replacement therapy (CRRT) may alter antibiotic pharmacokinetics and increase the risk of incorrect dosing. In a nested cohort within a large randomized controlled trial, we assessed the effect of higher (40 mL/kg per hour) and lower (25 mL/kg per hour) intensity CRRT on antibiotic pharmacokinetics.
  
  
  METHODS
  We collected serial blood samples to measure ciprofloxacin, meropenem, piperacillin-tazobactam, and vancomycin levels. We calculated extracorporeal clearance (CL), systemic CL, and volume of distribution (Vd) by non-linear mixed-effects modelling. We assessed the influence of CRRT intensity and other patient factors on antibiotic pharmacokinetics.
  
  
  RESULTS
  We studied 24 patients who provided 179 pairs of samples. Extracorporeal CL increased with higher-intensity CRRT but the increase was significant for vancomycin only (mean 28 versus 22 mL/minute; P = 0.0003). At any given prescribed CRRT effluent rate, extracorporeal CL of individual antibiotics varied widely, and the effluent-to-plasma concentration ratio decreased with increasing effluent flow. Overall, systemic CL varied to a greater extent than Vd, particularly for meropenem, piperacillin, and tazobactam, and large intra-individual differences were also observed. CRRT dose did not influence overall (systemic) CL, Vd, or half-life. The proportion of systemic CL due to CRRT varied widely and was high in some cases.
  
  
  CONCLUSIONS
  In patients receiving CRRT, there is great variability in antibiotic pharmacokinetics, which complicates an empiric approach to dosing and suggests the need for therapeutic drug monitoring. More research is required to investigate the apparent relative decrease in clearance at higher CRRT effluent rates.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00221013. Registered 14 September 2005.
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. darren.roberts@uq.edu.au.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.affiliation: Therapeutics Research Centre, School of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Queensland, 4102, Australia. xin.liu@uq.edu.au.|University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia, 5000, Australia. xin.liu@uq.edu.au.|The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South, Adelaide, South Australia, 5011, Australia. xin.liu@uq.edu.au.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.roberts2@uq.edu.au.|Department of Intensive Care Medicine, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Intensive Care Unit, St Vincent's Hospital, Victoria Street, Darlinghurst, NSW, 2010, Australia. pnair@stvincents.com.au.
authors.forename: Priya
authors.initials: P
authors.lastname: Nair
authors.affiliation: Intensive Care Unit, Nepean Hospital, Derby Street, Kingswood, NSW, 2747, Australia. l.cole@sydney.edu.au.
authors.forename: Louise
authors.initials: L
authors.lastname: Cole
authors.affiliation: Therapeutics Research Centre, School of Medicine, University of Queensland, Princess Alexandra Hospital, Ipswich Road, Brisbane, Queensland, 4102, Australia. m.roberts@uq.edu.au.|University of South Australia, City East Campus, GPO Box 2471, Adelaide, South Australia, 5000, Australia. m.roberts@uq.edu.au.|The Queen Elizabeth Hospital, 28 Woodville Road, Woodville South, Adelaide, South Australia, 5011, Australia. m.roberts@uq.edu.au.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.lipman@uq.edu.au.|Department of Intensive Care Medicine, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland, 4029, Australia. j.lipman@uq.edu.au.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Department of Intensive Care, Austin Health, 145 Studley Road, Heidelberg, Victoria, 3084, Australia. rinaldo.bellomo@austin.org.au.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016638:Critical Illness; D016903:Drug Monitoring; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents