title: Antibiotic dosing in the 'at risk' critically ill patient: Linking pathophysiology with pharmacokinetics/pharmacodynamics in sepsis and trauma patients.
abstract: BACKGROUND
  Critical illness, mediated by trauma or sepsis, can lead to physiological changes that alter the pharmacokinetics of antibiotics and may result in sub-therapeutic concentrations at the sites of infection. The first aim of this project is to identify the clinical characteristics of critically ill patients with significant trauma that have been recently admitted to ICU that may predict the dosing requirements for the antibiotic, cefazolin. The second aim of this is to identify the clinical characteristics of critically ill patients with sepsis that may predict the dosing requirements for the combination antibiotic, piperacillin-tazobactam.
  
  
  METHODS
  This is an observational pharmacokinetic study of patients with trauma (cefazolin) or with sepsis (piperacillin-tazobactam). Participants will have samples from blood and urine, collected at different intervals. Patients will also have a microdialysis catheter inserted into subcutaneous tissue to measure interstitial fluid penetration of the antibiotic. Participants will be administered sinistrin, indocyanine green and sodium bromide as well as have cardiac output monitoring performed and tetrapolar bioimpedance to determine physiological changes resulting from pathology. Analysis of samples will be performed using validated liquid chromatography tandem mass-spectrometry. Pharmacokinetic analysis will be performed using non-linear mixed effects modeling to determine individual and population pharmacokinetic parameters of antibiotics.
  
  
  CONCLUSIONS
  The study will describe cefazolin and piperacillin-tazobactam concentrations in plasma and the interstitial fluid of tissues in trauma and sepsis patients respectively. The results of this study will guide clinicians to effectively dose these antibiotics in order to maximize the concentration of antibiotics in the interstitial fluid of tissues.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia. j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.forename: Michael S
authors.initials: MS
authors.lastname: Roberts
authors.forename: Andrew
authors.initials: A
authors.lastname: Semark
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Udy
authors.forename: Carl Mj
authors.initials: CM
authors.lastname: Kirkpatrick
authors.forename: David L
authors.initials: DL
authors.lastname: Paterson
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Roberts
authors.forename: Peter
authors.initials: P
authors.lastname: Kruger
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman