Observational Study

. 2016 Mar 1:16:103.

doi: 10.1186/s12879-016-1421-6.

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

Jason A Roberts^{1

2}, Gordon Y S Choi³, Gavin M Joynt⁴, Sanjoy K Paul⁵, Renae Deans⁶, Sandra Peake⁷, Louise Cole⁸, Dianne Stephens⁹, Rinaldo Bellomo¹⁰, John Turnidge¹¹, Steven C Wallis¹², Michael S Roberts¹³, Darren M Roberts¹⁴, Melissa Lassig-Smith¹⁵, Therese Starr¹⁶, Jeffrey Lipman^{17

18}

Affiliations

¹ 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.
² Royal Brisbane & Women's Hospital, Queensland, Australia. j.roberts2@uq.edu.au.
³ Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China. gchoi@cuhk.edu.hk.
⁴ Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China. gavinmjoynt@cuhk.edu.hk.
⁵ Clinical Trials & Biostatistics Unit, QIMR Berghofer, Queensland, Australia. sanjoy.paul@qimrberghofer.edu.au.
⁶ 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.
⁷ The Queen Elizabeth Hospital, South Australia, Australia. Sandra.Peake@sa.gov.au.
⁸ Nepean Hospital, New South Wales, Australia. l.cole@sydney.edu.au.
⁹ Royal Darwin Hospital, Northern Territory, Australia. Dianne.stephens@nt.gov.au.
¹⁰ Austin Hospital, Victoria, Australia. Rinaldo.BELLOMO@austin.org.au.
¹¹ Royal Women's and Children's Hospital, Queensland, Australia. John.Turnidge@health.sa.gov.au.
¹² 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.
¹³ Therapeutics Research Unit, The University of Queensland, Queensland, Australia. m.roberts@uq.edu.au.
¹⁴ 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.
¹⁵ Royal Brisbane & Women's Hospital, Queensland, Australia. Melissa.Lassig-Smith@health.qld.gov.au.
¹⁶ Royal Brisbane & Women's Hospital, Queensland, Australia. Therese.Starr@health.qld.gov.au.
¹⁷ 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.
¹⁸ Royal Brisbane & Women's Hospital, Queensland, Australia. j.lipman@uq.edu.au.

PMID: 26932762
PMCID: PMC4773999
DOI: 10.1186/s12879-016-1421-6

Observational Study

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

Jason A Roberts et al. BMC Infect Dis. 2016.

. 2016 Mar 1:16:103.

doi: 10.1186/s12879-016-1421-6.

Authors

Affiliations

¹ 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.
² Royal Brisbane & Women's Hospital, Queensland, Australia. j.roberts2@uq.edu.au.
³ Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China. gchoi@cuhk.edu.hk.
⁴ Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, Special Administrative Region, China. gavinmjoynt@cuhk.edu.hk.
⁵ Clinical Trials & Biostatistics Unit, QIMR Berghofer, Queensland, Australia. sanjoy.paul@qimrberghofer.edu.au.
⁶ 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.
⁷ The Queen Elizabeth Hospital, South Australia, Australia. Sandra.Peake@sa.gov.au.
⁸ Nepean Hospital, New South Wales, Australia. l.cole@sydney.edu.au.
⁹ Royal Darwin Hospital, Northern Territory, Australia. Dianne.stephens@nt.gov.au.
¹⁰ Austin Hospital, Victoria, Australia. Rinaldo.BELLOMO@austin.org.au.
¹¹ Royal Women's and Children's Hospital, Queensland, Australia. John.Turnidge@health.sa.gov.au.
¹² 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.
¹³ Therapeutics Research Unit, The University of Queensland, Queensland, Australia. m.roberts@uq.edu.au.
¹⁴ 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.
¹⁵ Royal Brisbane & Women's Hospital, Queensland, Australia. Melissa.Lassig-Smith@health.qld.gov.au.
¹⁶ Royal Brisbane & Women's Hospital, Queensland, Australia. Therese.Starr@health.qld.gov.au.
¹⁷ 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.
¹⁸ Royal Brisbane & Women's Hospital, Queensland, Australia. j.lipman@uq.edu.au.

PMID: 26932762
PMCID: PMC4773999
DOI: 10.1186/s12879-016-1421-6

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.

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Figures

**Fig. 1**
Antibiotic Pharmacokinetic Sampling Schedule

See this image and copyright information in PMC

Cited by

Effect of Obesity on the Population Pharmacokinetics of Fluconazole in Critically Ill Patients.
Alobaid AS, Wallis SC, Jarrett P, Starr T, Stuart J, Lassig-Smith M, Mejia JL, Roberts MS, Sinnollareddy MG, Roger C, Lipman J, Roberts JA. Alobaid AS, et al. Antimicrob Agents Chemother. 2016 Oct 21;60(11):6550-6557. doi: 10.1128/AAC.01088-16. Print 2016 Nov. Antimicrob Agents Chemother. 2016. PMID: 27550344 Free PMC article.
A Robust Statistical Approach to Analyse Population Pharmacokinetic Data in Critically Ill Patients Receiving Renal Replacement Therapy.
Paul SK, Roberts JA, Lipman J, Deans R, Samanta M. Paul SK, et al. Clin Pharmacokinet. 2019 Feb;58(2):263-270. doi: 10.1007/s40262-018-0690-1. Clin Pharmacokinet. 2019. PMID: 30094712
Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy.
Roberts JA, Ulldemolins M, Liu X, Baptista JP, Bilgrami I, Boidin C, Brinkmann A, Castro P, Choi G, Cole L, De Waele JJ, Deans R, Donnellan S, Eastwood GM, Frey OR, Goutelle S, Gresham R, Jamal JA, Joynt GM, Kanji S, Kluge S, König C, Koulouras VP, Lassig-Smith M, Laterre PF, Lee A, Lefrant JY, Lei K, Leung P, Llaurado-Serra M, Martin-Loeches I, Nor MBM, Mudaliar Y, Ostermann M, Paul SK, Peake SL, Rello J, Roberts DM, Roberts MS, Richards B, Rodríguez A, Roehr AC, Roger C, Seoane L, Sinnollareddy M, Sousa E, Soy D, Spring A, Starr T, Stephens D, Taccone FS, Thomas J, Turnidge J, Valkonen M, Varghese JM, Wallis SC, Walker RJ, Williams T, Wilson LC, Wittebole X, Wright DFB, Zikou XT, Bellomo R, Lipman J; SMARRT Study Collaborators. Roberts JA, et al. Intensive Care Med. 2025 Aug 13. doi: 10.1007/s00134-025-08067-w. Online ahead of print. Intensive Care Med. 2025. PMID: 40801954
Pharmacokinetic/Pharmacodynamic Considerations of Beta-Lactam Antibiotics in Adult Critically Ill Patients.
Masich AM, Heavner MS, Gonzales JP, Claeys KC. Masich AM, et al. Curr Infect Dis Rep. 2018 Apr 4;20(5):9. doi: 10.1007/s11908-018-0613-1. Curr Infect Dis Rep. 2018. PMID: 29619607 Review.
Therapeutic drug monitoring-guided continuous infusion of piperacillin/tazobactam significantly improves pharmacokinetic target attainment in critically ill patients: a retrospective analysis of four years of clinical experience.
Richter DC, Frey O, Röhr A, Roberts JA, Köberer A, Fuchs T, Papadimas N, Heinzel-Gutenbrunner M, Brenner T, Lichtenstern C, Weigand MA, Brinkmann A. Richter DC, et al. Infection. 2019 Dec;47(6):1001-1011. doi: 10.1007/s15010-019-01352-z. Epub 2019 Aug 31. Infection. 2019. PMID: 31473974

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References

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

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

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