. 2021 Apr 26;72(8):1369-1378.

doi: 10.1093/cid/ciaa224.

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

Jason A Roberts^{1

2

3

4}, Gavin M Joynt⁵, Anna Lee⁵, Gordon Choi⁵, Rinaldo Bellomo⁶, Salmaan Kanji^{7

8}, M Yugan Mudaliar^{9

10}, Sandra L Peake^{11

12

13}, Dianne Stephens^{14

15

16}, Fabio Silvio Taccone¹⁷, Marta Ulldemolins^{18

19

20}, Miia Maaria Valkonen²¹, Julius Agbeve²², João P Baptista²³, Vasileios Bekos²⁴, Clement Boidin^{1

25

26}, Alexander Brinkmann²⁷, Luke Buizen²⁸, Pedro Castro^{29

30}, C Louise Cole^{10

31}, Jacques Creteur¹⁷, Jan J De Waele³², Renae Deans¹, Glenn M Eastwood⁶, Leslie Escobar³³, Charles Gomersall⁵, Rebecca Gresham³¹, Janattul Ain Jamal³⁴, Stefan Kluge³⁵, Christina König^{35

36}, Vasilios P Koulouras³⁷, Melissa Lassig-Smith², Pierre-Francois Laterre³⁸, Katie Lei³⁹, Patricia Leung⁵, Jean-Yves Lefrant⁴⁰, Mireia Llauradó-Serra⁴¹, Ignacio Martin-Loeches^{18

42}, Mohd Basri Mat Nor⁴³, Marlies Ostermann³⁹, Suzanne L Parker¹, Jordi Rello⁴⁴, Darren M Roberts¹, Michael S Roberts^{45

46

47}, Brent Richards⁴⁸, Alejandro Rodríguez^{49

50}, Anka C Roehr⁵¹, Claire Roger⁴⁰, Leonardo Seoane^{52

53}, Mahipal Sinnollareddy^{45

46}, Eduardo Sousa²³, Dolors Soy^{30

54}, Anna Spring²⁴, Therese Starr², Jane Thomas¹⁴, John Turnidge¹², Steven C Wallis¹, Tricia Williams^{11

12

13}, Xavier Wittebole³⁸, Xanthi T Zikou⁵⁵, Sanjoy K Paul²⁸, Jeffrey Lipman^{1

2}; SMARRT Study Collaborators and the ANZICS Clinical Trials Group

Collaborators, Affiliations

Collaborators

SMARRT Study Collaborators and the ANZICS Clinical Trials Group:
Max Andresen, Sónia F Baltazar, Saber Barbar, Eulália Costa, Dominique Durand, Ricardo Freitas, Otto R Frey, Yarmarly Guerra Valero, Margaret Haughton, Andreas Koeberer, Marin Kollef, Kerenaftali Klein, Ravindra Mehta, Cathy McKenzie, Laurent Muller, Priya Nair, Vineet Nayyar, Jenny L Ordóñez Mejia, Georgia-Laura Panagou, Jody Paxton, Leah Peck, Mayukh Samanta, Jean-Louise Vincent, Ruth Wan, Helen Young

Affiliations

¹ The University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia.
² Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia.
³ Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia.
⁴ Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
⁵ Department of Anesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
⁶ Department of Intensive Care, Austin Hospital, Heidelberg and School of Medicine, The University of Melbourne, Melbourne, Australia.
⁷ Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada.
⁸ The Ottawa Hospital Research Institute, Ottawa, Canada.
⁹ Intensive Care Unit, Westmead Hospital, Sydney, Australia.
¹⁰ Medical School, University of Sydney, Sydney, Australia.
¹¹ Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville, Australia.
¹² School of Medicine, University of Adelaide, Adelaide, Australia.
¹³ School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
¹⁴ Intensive Care Unit, Royal Darwin Hospital, Darwin, Australia.
¹⁵ Flinders University, Adelaide, Australia.
¹⁶ National Critical Care and Trauma Response Centre, Darwin, Australia.
¹⁷ Department of Intensive Care, Erasme Hospital, Brussels, Belgium.
¹⁸ Critical Care Department, Corporació Sanitària Parc Taulí, Sabadell, Spain.
¹⁹ Fundació Privada Clínic per la Recerca Biomèdica, Barcelona, Spain.
²⁰ Infectious Diseases-Internal Medicine Departments, Bellvitge University Hospital, l'Hospitalet de Llobregat, Spain.
²¹ Intensive Care Medicine, Department of Perioperative, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
²² Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Herston, Australia.
²³ Intensive Care Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
²⁴ Intensive Care Unit, Naval and Veterans Hospital of Athens, Athens, Greece.
²⁵ Université Claude Bernard Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive, Lyon, France.
²⁶ Hôpital Pierre Garraud, Hospices Civils de Lyon, Lyon, France.
²⁷ Department of Anesthesia and Critical Care Medicine, General Hospital of Heidenheim, Heidenheim, Germany.
²⁸ Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia.
²⁹ Medical Intensive Care Unit, ICMiD. Hospital Clínic de Barcelona, Barcelona, Spain.
³⁰ IDIBAPS, University of Barcelona, Barcelona, Spain.
³¹ Intensive Care Unit, Nepean Hospital, Sydney, Australia.
³² Department of Critical Care Medicine; Ghent University Hospital, Ghent, Belgium.
³³ Faculty of Medicine, Universidad de Chile, Santiago, Chile.
³⁴ Department of Pharmacy, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia.
³⁵ Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁶ Hospital Pharmacy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
³⁷ Intensive Care Unit Department, University Hospital of Ioannina, Ioannina, Greece.
³⁸ Intensive Care Unit, Clinique Universitaire St Luc UCL, Brussels, Belgium.
³⁹ Guy's and St Thomas Hospital, London, United Kingdom.
⁴⁰ Intensive Care Unit, Nîmes University Hospital (Centre Hospitalo Universitaire Nimes), Nimes, France.
⁴¹ Department of Nursing, School of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
⁴² Multidisciplinary Intensive Care Research Organization (MICRO), St James Hospital, Dublin, Ireland.
⁴³ Department of Anesthesiology and Intensive Care, School of Medicine, International Islamic University Malaysia, Selangor, Malaysia.
⁴⁴ CIBERES, Vall d'Hebron Institute of Research, Barcelona, Spain.
⁴⁵ School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
⁴⁶ Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia.
⁴⁷ Translational Research Institute, The University of Queensland, Buranda, Australia.
⁴⁸ Intensive Care Unit, Gold Coast University Hospital, Gold Coast, Australia.
⁴⁹ Intensive Care Unit, University Hospital Joan XXIII, Tarragona, Spain.
⁵⁰ Rovira i Virgili University, IISPV/CIBERES, Tarragona, Spain.
⁵¹ Department of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany.
⁵² Faculty of Medicine, An University of Queensland, New Orleans, Louisiana, USA.
⁵³ Intensive Care Unit, Ochsner Health System, New Orleans, Louisiana, USA.
⁵⁴ Pharmacy Department, Division of Medicines. Hospital Clínic de Barcelona, Barcelona, Spain.
⁵⁵ Nephrology, University Hospital of Ioannina, Ioannina, Greece.

PMID: 32150603
DOI: 10.1093/cid/ciaa224

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

Jason A Roberts et al. Clin Infect Dis. 2021.

. 2021 Apr 26;72(8):1369-1378.

doi: 10.1093/cid/ciaa224.

Authors

Collaborators

SMARRT Study Collaborators and the ANZICS Clinical Trials Group:
Max Andresen, Sónia F Baltazar, Saber Barbar, Eulália Costa, Dominique Durand, Ricardo Freitas, Otto R Frey, Yarmarly Guerra Valero, Margaret Haughton, Andreas Koeberer, Marin Kollef, Kerenaftali Klein, Ravindra Mehta, Cathy McKenzie, Laurent Muller, Priya Nair, Vineet Nayyar, Jenny L Ordóñez Mejia, Georgia-Laura Panagou, Jody Paxton, Leah Peck, Mayukh Samanta, Jean-Louise Vincent, Ruth Wan, Helen Young

Affiliations

¹ The University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Queensland, Australia.
² Intensive Care Services, Royal Brisbane and Women's Hospital, Brisbane, Australia.
³ Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia.
⁴ Centre for Translational Anti-infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.
⁵ Department of Anesthesia and Intensive Care, The Chinese University of Hong Kong, Shatin, Hong Kong.
⁶ Department of Intensive Care, Austin Hospital, Heidelberg and School of Medicine, The University of Melbourne, Melbourne, Australia.
⁷ Department of Pharmacy, The Ottawa Hospital, Ottawa, Canada.
⁸ The Ottawa Hospital Research Institute, Ottawa, Canada.
⁹ Intensive Care Unit, Westmead Hospital, Sydney, Australia.
¹⁰ Medical School, University of Sydney, Sydney, Australia.
¹¹ Department of Intensive Care Medicine, The Queen Elizabeth Hospital, Woodville, Australia.
¹² School of Medicine, University of Adelaide, Adelaide, Australia.
¹³ School of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia.
¹⁴ Intensive Care Unit, Royal Darwin Hospital, Darwin, Australia.
¹⁵ Flinders University, Adelaide, Australia.
¹⁶ National Critical Care and Trauma Response Centre, Darwin, Australia.
¹⁷ Department of Intensive Care, Erasme Hospital, Brussels, Belgium.
¹⁸ Critical Care Department, Corporació Sanitària Parc Taulí, Sabadell, Spain.
¹⁹ Fundació Privada Clínic per la Recerca Biomèdica, Barcelona, Spain.
²⁰ Infectious Diseases-Internal Medicine Departments, Bellvitge University Hospital, l'Hospitalet de Llobregat, Spain.
²¹ Intensive Care Medicine, Department of Perioperative, Intensive Care, and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
²² Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Herston, Australia.
²³ Intensive Care Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
²⁴ Intensive Care Unit, Naval and Veterans Hospital of Athens, Athens, Greece.
²⁵ Université Claude Bernard Lyon 1, UMR CNRS 5558, Laboratoire de Biométrie et Biologie Évolutive, Lyon, France.
²⁶ Hôpital Pierre Garraud, Hospices Civils de Lyon, Lyon, France.
²⁷ Department of Anesthesia and Critical Care Medicine, General Hospital of Heidenheim, Heidenheim, Germany.
²⁸ Melbourne EpiCentre, University of Melbourne and Melbourne Health, Melbourne, Australia.
²⁹ Medical Intensive Care Unit, ICMiD. Hospital Clínic de Barcelona, Barcelona, Spain.
³⁰ IDIBAPS, University of Barcelona, Barcelona, Spain.
³¹ Intensive Care Unit, Nepean Hospital, Sydney, Australia.
³² Department of Critical Care Medicine; Ghent University Hospital, Ghent, Belgium.
³³ Faculty of Medicine, Universidad de Chile, Santiago, Chile.
³⁴ Department of Pharmacy, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, Malaysia.
³⁵ Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
³⁶ Hospital Pharmacy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
³⁷ Intensive Care Unit Department, University Hospital of Ioannina, Ioannina, Greece.
³⁸ Intensive Care Unit, Clinique Universitaire St Luc UCL, Brussels, Belgium.
³⁹ Guy's and St Thomas Hospital, London, United Kingdom.
⁴⁰ Intensive Care Unit, Nîmes University Hospital (Centre Hospitalo Universitaire Nimes), Nimes, France.
⁴¹ Department of Nursing, School of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
⁴² Multidisciplinary Intensive Care Research Organization (MICRO), St James Hospital, Dublin, Ireland.
⁴³ Department of Anesthesiology and Intensive Care, School of Medicine, International Islamic University Malaysia, Selangor, Malaysia.
⁴⁴ CIBERES, Vall d'Hebron Institute of Research, Barcelona, Spain.
⁴⁵ School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
⁴⁶ Therapeutics Research Centre, Basil Hetzel Institute for Translational Health Research, The Queen Elizabeth Hospital, Adelaide, Australia.
⁴⁷ Translational Research Institute, The University of Queensland, Buranda, Australia.
⁴⁸ Intensive Care Unit, Gold Coast University Hospital, Gold Coast, Australia.
⁴⁹ Intensive Care Unit, University Hospital Joan XXIII, Tarragona, Spain.
⁵⁰ Rovira i Virgili University, IISPV/CIBERES, Tarragona, Spain.
⁵¹ Department of Pharmacy, General Hospital of Heidenheim, Heidenheim, Germany.
⁵² Faculty of Medicine, An University of Queensland, New Orleans, Louisiana, USA.
⁵³ Intensive Care Unit, Ochsner Health System, New Orleans, Louisiana, USA.
⁵⁴ Pharmacy Department, Division of Medicines. Hospital Clínic de Barcelona, Barcelona, Spain.
⁵⁵ Nephrology, University Hospital of Ioannina, Ioannina, Greece.

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.

Keywords: beta-lactam; continuous renal replacement therapy; extended daily dialysis; pharmacokinetic; renal clearance.

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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

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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

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