Jason A Roberts1,2,3,4, Gavin M Joynt5, Anna Lee5, Gordon Choi5, Rinaldo Bellomo6, Salmaan Kanji7,8, M Yugan Mudaliar9,10, Sandra L Peake11,12,13, Dianne Stephens14,15,16, Fabio Silvio Taccone17, Marta Ulldemolins18,19,20, Miia Maaria Valkonen21, Julius Agbeve22, João P Baptista23, Vasileios Bekos24, Clement Boidin1,25,26, Alexander Brinkmann27, Luke Buizen28, Pedro Castro29,30, C Louise Cole10,31, Jacques Creteur17, Jan J De Waele32, Renae Deans1, Glenn M Eastwood6, Leslie Escobar33, Charles Gomersall5, Rebecca Gresham31, Janattul Ain Jamal34, Stefan Kluge35, Christina König35,36, Vasilios P Koulouras37, Melissa Lassig-Smith2, Pierre-Francois Laterre38, Katie Lei39, Patricia Leung5, Jean-Yves Lefrant40, Mireia Llauradó-Serra41, Ignacio Martin-Loeches18,42, Mohd Basri Mat Nor43, Marlies Ostermann39, Suzanne L Parker1, Jordi Rello44, Darren M Roberts1, Michael S Roberts45,46,47, Brent Richards48, Alejandro Rodríguez49,50, Anka C Roehr51, Claire Roger40, Leonardo Seoane52,53, Mahipal Sinnollareddy45,46, Eduardo Sousa23, Dolors Soy30,54, Anna Spring24, Therese Starr2, Jane Thomas14, John Turnidge12, Steven C Wallis1, Tricia Williams11,12,13, Xavier Wittebole38, Xanthi T Zikou55, Sanjoy K Paul28, Jeffrey Lipman1,2. 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.
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.
BACKGROUND: The optimal dosing of antibiotics in critically illpatients receiving renal replacement therapy (RRT) remains unclear. In this study, we describe the variability in RRT techniques and antibiotic dosing in critically illpatients 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 illpatients 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.
Authors: Laura Evans; Andrew Rhodes; Waleed Alhazzani; Massimo Antonelli; Craig M Coopersmith; Craig French; Flávia R Machado; Lauralyn Mcintyre; Marlies Ostermann; Hallie C Prescott; Christa Schorr; Steven Simpson; W Joost Wiersinga; Fayez Alshamsi; Derek C Angus; Yaseen Arabi; Luciano Azevedo; Richard Beale; Gregory Beilman; Emilie Belley-Cote; Lisa Burry; Maurizio Cecconi; John Centofanti; Angel Coz Yataco; Jan De Waele; R Phillip Dellinger; Kent Doi; Bin Du; Elisa Estenssoro; Ricard Ferrer; Charles Gomersall; Carol Hodgson; Morten Hylander Møller; Theodore Iwashyna; Shevin Jacob; Ruth Kleinpell; Michael Klompas; Younsuck Koh; Anand Kumar; Arthur Kwizera; Suzana Lobo; Henry Masur; Steven McGloughlin; Sangeeta Mehta; Yatin Mehta; Mervyn Mer; Mark Nunnally; Simon Oczkowski; Tiffany Osborn; Elizabeth Papathanassoglou; Anders Perner; Michael Puskarich; Jason Roberts; William Schweickert; Maureen Seckel; Jonathan Sevransky; Charles L Sprung; Tobias Welte; Janice Zimmerman; Mitchell Levy Journal: Intensive Care Med Date: 2021-10-02 Impact factor: 17.440
Authors: Mohammad H Al-Shaer; Kelly Maguigan; Jennifer Ashton; Veena Venugopalan; Molly E Droege; Carolyn D Philpott; Christopher A Droege; Daniel P Healy; Eric W Mueller; Charles A Peloquin Journal: Antimicrob Agents Chemother Date: 2021-10-18 Impact factor: 5.938
Authors: Julia Zimmer; Anka C Röhr; Stefan Kluge; Jonas Faller; Otto R Frey; Dominic Wichmann; Christina König Journal: Antibiotics (Basel) Date: 2021-02-28
Authors: Craig R Rayner; Patrick F Smith; David Andes; Kayla Andrews; Hartmut Derendorf; Lena E Friberg; Debra Hanna; Alex Lepak; Edward Mills; Thomas M Polasek; Jason A Roberts; Virna Schuck; Mark J Shelton; David Wesche; Karen Rowland-Yeo Journal: Clin Pharmacol Ther Date: 2021-03-09 Impact factor: 6.875
Authors: Christian Lanckohr; Christian Boeing; Jan J De Waele; Dylan W de Lange; Jeroen Schouten; Menno Prins; Maarten Nijsten; Pedro Povoa; Andrew Conway Morris; Hendrik Bracht Journal: Ann Intensive Care Date: 2021-08-26 Impact factor: 6.925