The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients: Data From the Multinational Sampling Antibiotics in Renal Replacement Therapy Study

Roberts JA 1 , Joynt GM 2 , Lee A 2 , Choi G 2 , Bellomo R 3 , Kanji S 4 Show all authors , Mudaliar MY 5 , Peake SL 6 , Stephens D 7 , Taccone FS 8 , Ulldemolins M 9 , Valkonen MM 10 , Agbeve J 11 , Baptista JP 12 , Bekos V 13 , Boidin C 1 , Brinkmann A 14 , Buizen L 15 , Castro P 16 , Cole CL 17 , Creteur J 8 , De Waele JJ 18 , Deans R 1 , Eastwood GM 3 , Escobar L 19 , Gomersall C 2 , Gresham R 20 , Jamal JA 21 , Kluge S 22 , König C 22 , Koulouras VP 23 , Lassig-Smith M 24 , Laterre PF 25 , Lei K 26 , Leung P 2 , Lefrant JY 27 , Llauradó-Serra M 28 , Martin-Loeches I 9 , Mat Nor MB 29 , Ostermann M 26 , Parker SL 1 , Rello J 30 , Roberts DM 1 , Roberts MS 31 , Richards B 32 , Rodríguez A 33 , Roehr AC 34 , Roger C 27 , Seoane L 35 , Sinnollareddy M 31 , Sousa E 12 , Soy D 36 , Spring A 13 , Starr T 24 , Thomas J 7 , Turnidge J 37 , Wallis SC 1 , Williams T 6 , Wittebole X 25 , Zikou XT 38 , Paul SK 15 , Lipman J 1 , SMARRT Study Collaborators and the ANZICS Clinical Trials Group

Affiliations 

  • 1 The University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia
  • 2 Department of Anesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong
  • 3 Department of Intensive Care, Austin Hospital, Heidelberg and School of Medicine, The University of Melbourne, Melbourne, Australia
  • 4 Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada
  • 5 Intensive Care Unit, Westmead Hospital, Sydney, Australia
  • 6 Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville, Australia
  • 7 Intensive Care Unit, Royal Darwin Hospital, Darwin, Australia
  • 8 Department of Intensive Care, Erasme Hospital, Brussels, Belgium
  • 9 Critical Care Department, Corporació Sanitària Parc Taulí, Sabadell, Spain
  • 10 Intensive Care Medicine, Department of Perioperative, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
  • 11 Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Herston, Australia
  • 12 Intensive Care Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal
  • 13 Intensive Care Unit, Naval and Veterans Hospital of Athens, Athens, Greece
  • 14 Department of Anesthesia and Critical Care Medicine, General Hospital of Heidenheim, Heidenheim, Germany
  • 15 Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia
  • 16 Medical Intensive Care Unit, ICMiD. Hospital Clínic de Barcelona, Barcelona, Spain
  • 17 Medical School, University of Sydney, Sydney, Australia
  • 18 Department of Critical Care Medicine; Ghent University Hospital, Ghent, Belgium
  • 19 Faculty of Medicine, Universidad de Chile, Santiago, Chile
  • 20 Intensive Care Unit, Nepean Hospital, Sydney, Australia
  • 21 Department of Pharmacy, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia
  • 22 Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  • 23 Intensive Care Unit Department, University Hospital of Ioannina, Ioannina, Greece
  • 24 Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia
  • 25 Intensive Care Unit, Clinique Universitaire St Luc UCL, Brussels, Belgium
  • 26 Guy's and St Thomas Hospital, London, United Kingdom
  • 27 Intensive Care Unit, Nîmes University Hospital (Centre Hospitalo Universitaire Nimes), Nimes, France
  • 28 Department of Nursing, School of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain
  • 29 Department of Anesthesiology and Intensive Care, School of Medicine, International Islamic University Malaysia, Selangor, Malaysia
  • 30 CIBERES, Vall d'Hebron Institute of Research, Barcelona, Spain
  • 31 School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
  • 32 Intensive Care Unit, Gold Coast University Hospital, Gold Coast, Australia
  • 33 Intensive Care Unit, University Hospital Joan XXIII, Tarragona, Spain
  • 34 Department of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany
  • 35 Faculty of Medicine, An University of Queensland, New Orleans, Louisiana, USA
  • 36 IDIBAPS, University of Barcelona, Barcelona, Spain
  • 37 School of Medicine, University of Adelaide, Adelaide, Australia
  • 38 Nephrology, University Hospital of Ioannina, Ioannina, Greece
Clin Infect Dis, 2021 04 26;72(8):1369-1378.
PMID: 32150603 DOI: 10.1093/cid/ciaa224

Abstract

BACKGROUND: The optimal dosing of antibiotics in critically ill patients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically ill patients receiving RRT and relate observed trough antibiotic concentrations to optimal targets.

METHODS: We performed a prospective, observational, multinational, pharmacokinetic study in 29 intensive care units from 14 countries. We collected demographic, clinical, and RRT data. We measured trough antibiotic concentrations of meropenem, piperacillin-tazobactam, and vancomycin and related them to high- and low-target trough concentrations.

RESULTS: We studied 381 patients and obtained 508 trough antibiotic concentrations. There was wide variability (4-8-fold) in antibiotic dosing regimens, RRT prescription, and estimated endogenous renal function. The overall median estimated total renal clearance (eTRCL) was 50 mL/minute (interquartile range [IQR], 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (P < .05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin was 78.6 mg/L (49.5-127.3), tazobactam was 9.5 mg/L (6.3-14.2), and vancomycin was 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, and 72% and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin, and vancomycin, respectively.

CONCLUSIONS: In critically ill patients treated with RRT, antibiotic dosing regimens, RRT prescription, and eTRCL varied markedly and resulted in highly variable antibiotic concentrations that failed to meet therapeutic targets in many patients.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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