SaMpling Antibiotics in Renal Replacement Therapy (SMARRT): An observational pharmacokinetic study in critically ill patients

Jason A. Roberts, Gordon Y.S. Choi, Gavin M. Joynt, Sanjoy K. Paul, Renae Deans, Sandra Peake, Louise Cole, Dianne Stephens, Rinaldo Bellomo, John Turnidge, Steven C. Wallis, Michael S. Roberts, Darren M. Roberts, Melissa Lassig-Smith, Therese Starr, Jeffrey Lipman

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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/Design: 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. Discussion: 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. Trial registration: Australian New Zealand Clinical Trial Registry ( ACTRN12613000241730 ) registered 28 February 2013.

Original languageEnglish
Article number103
Number of pages8
JournalBMC Infectious Diseases
Volume16
DOIs
Publication statusPublished - 1 Mar 2016
Externally publishedYes

Bibliographical note

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Keywords

  • Antibiotic dosing
  • Dialysis
  • Linezolid
  • Meropenem
  • Pharmacodynamics
  • Pharmacokinetics
  • Piperacillin
  • Sepsis
  • Tazobactam
  • Vancomycin

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