title: SaMpling Antibiotics in Renal Replacement Therapy (SMARRT): an observational pharmacokinetic study in critically ill patients.
abstract: BACKGROUND
  Optimal antibiotic dosing is key to maximising patient survival, and minimising the emergence of bacterial resistance. Evidence-based antibiotic dosing guidelines for critically ill patients receiving RRT are currently not available, as RRT techniques and settings vary greatly between ICUs and even individual patients. We aim to develop a robust, evidence-based antibiotic dosing guideline for critically ill patients receiving various forms of RRT. We further aim to observe whether therapeutic antibiotic concentrations are associated with reduced 28-day mortality.
  
  
  METHODS
  We designed a multi-national, observational pharmacokinetic study in critically ill patients requiring RRT. The study antibiotics will be vancomycin, linezolid, piperacillin/tazobactam and meropenem. Pharmacokinetic sampling of each patient's blood, RRT effluent and urine will take place during two separate dosing intervals. In addition, a comprehensive data set, which includes the patients' demographic and clinical parameters, as well as modality, technique and settings of RRT, will be collected. Pharmacokinetic data will be analysed using a population pharmacokinetic approach to identify covariates associated with changes in pharmacokinetic parameters in critically ill patients with AKI who are undergoing RRT for the five commonly prescribed antibiotics.
  
  
  CONCLUSIONS
  Using the comprehensive data set collected, the pharmacokinetic profile of the five antibiotics will be constructed, including identification of RRT and other factors indicative of the need for altered antibiotic dosing requirements. This will enable us to develop a dosing guideline for each individual antibiotic that is likely to be relevant to any critically ill patient with acute kidney injury receiving any of the included forms of RRT.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trial Registry ( ACTRN12613000241730 ) registered 28 February 2013.
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia. j.roberts2@uq.edu.au.|Royal Brisbane & Women's Hospital, Queensland, Australia. j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China. gchoi@cuhk.edu.hk.
authors.forename: Gordon Y S
authors.initials: GY
authors.lastname: Choi
authors.affiliation: Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China. gavinmjoynt@cuhk.edu.hk.
authors.forename: Gavin M
authors.initials: GM
authors.lastname: Joynt
authors.affiliation: Clinical Trials & Biostatistics Unit, QIMR Berghofer, Queensland, Australia. sanjoy.paul@qimrberghofer.edu.au.
authors.forename: Sanjoy K
authors.initials: SK
authors.lastname: Paul
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia. renae.deans@gmail.com.
authors.forename: Renae
authors.initials: R
authors.lastname: Deans
authors.affiliation: The Queen Elizabeth Hospital, South Australia, Australia. Sandra.Peake@sa.gov.au.
authors.forename: Sandra
authors.initials: S
authors.lastname: Peake
authors.affiliation: Nepean Hospital, New South Wales, Australia. l.cole@sydney.edu.au.
authors.forename: Louise
authors.initials: L
authors.lastname: Cole
authors.affiliation: Royal Darwin Hospital, Northern Territory, Australia. Dianne.stephens@nt.gov.au.
authors.forename: Dianne
authors.initials: D
authors.lastname: Stephens
authors.affiliation: Austin Hospital, Victoria, Australia. Rinaldo.BELLOMO@austin.org.au.
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Bellomo
authors.affiliation: Royal Women's and Children's Hospital, Queensland, Australia. John.Turnidge@health.sa.gov.au.
authors.forename: John
authors.initials: J
authors.lastname: Turnidge
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia. s.wallis@uq.edu.au.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Wallis
authors.affiliation: Therapeutics Research Unit, The University of Queensland, Queensland, 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, Herston, Queensland, 4029, Australia. 1darren1@gmail.com.
authors.forename: Darren M
authors.initials: DM
authors.lastname: Roberts
authors.affiliation: Royal Brisbane & Women's Hospital, Queensland, Australia. Melissa.Lassig-Smith@health.qld.gov.au.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lassig-Smith
authors.affiliation: Royal Brisbane & Women's Hospital, Queensland, Australia. Therese.Starr@health.qld.gov.au.
authors.forename: Therese
authors.initials: T
authors.lastname: Starr
authors.affiliation: Burns Trauma and Critical Care Research Centre, The University of Queensland, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Herston, Queensland, 4029, Australia. j.lipman@uq.edu.au.|Royal Brisbane & Women's Hospital, Queensland, Australia. j.lipman@uq.edu.au.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002985:Clinical Protocols; D016638:Critical Illness; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017582:Renal Replacement Therapy; D018805:Sepsis / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D054316:Biomarkers, Pharmacological