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2. 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

Author

Roberts, Jason, Joynt, Gavin, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, Cole, C Louise, Creteur, Jacques, de Waele, Jan, Deans, Renae, Eastwood, Glenn, Escobar, Leslie, Gomersall, Charles, Gresham, Rebecca, Jamal, Janattul Ain, Kluge, Stefan, König, Christina, Koulouras, Vasilios, Lassig-Smith, Melissa, Laterre, Pierre-Francois, Lei, Katie, Leung, Patricia, Lefrant, Jean-Yves, Llauradó-Serra, Mireia, Martin-Loeches, Ignacio, Mat Nor, Mohd Basri, Ostermann, Marlies, Parker, Suzanne, Rello, Jordi, Roberts, Darren, Roberts, Michael, Richards, Brent, Rodríguez, Alejandro, Roehr, Anka, Roger, Claire, Seoane, Leonardo, Sinnollareddy, Mahipal, Sousa, Eduardo, Soy, Dolors, Spring, Anna, Starr, Therese, Thomas, Jane, Turnidge, John, Wallis, Steven, Williams, Tricia, Wittebole, Xavier, Zikou, Xanthi, Paul, Sanjoy, Lipman, Jeffrey, Andresen, Max, Baltazar, Sónia, Barbar, Saber, Costa, Eulália, Durand, Dominique, Freitas, Ricardo, Frey, Otto, Guerra Valero, Yarmarly, Haughton, Margaret, Koeberer, Andreas, Kollef, Marin, Klein, Kerenaftali, Mehta, Ravindra, Mckenzie, Cathy, Muller, Laurent, Nair, Priya, Nayyar, Vineet, Ordóñez Mejia, Jenny, Panagou, Georgia-Laura, Paxton, Jody, Peck, Leah, Samanta, Mayukh, Vincent, Jean-Louise, Wan, Ruth, Young, Helen, University of Southern Queensland (USQ), Royal Brisbane & Women's Hospital [Brisbane, Australia] (RBWH), Princess Alexandra Hospital, Brisbane, SMARRT Study, ANZICS Clinical Trials Group, The Chinese University of Hong Kong [Hong Kong], Austin Hospital [Melbourne], Austin Health, The Ottawa Hospital, The Ottawa Hospital Research Institute, Centre for Rehabilitation Research and Development, 505 Smyth Road, Ottawa, ON, Canada, K1H 8M2., Westmead Hospital [Sydney], The University of Sydney, The Queen Elizabeth Hospital (TQEH), University of Adelaide, Monash University [Melbourne], Royal Darwin Hospital, Flinders University [Adelaide, Australia], National Critical Care and Trauma Response Centre (Darwin) (NCCTRC), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Corporació Sanitària Parc Taulí, Barcelona Biomedical Research Park (PRBB), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, QIMR Berghofer Medical Research Institute, Centro Hospitalar e Universitário [Coimbra], Athens Naval Hospital, University of Queensland [Brisbane], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Kliniken Landkreis Heidenheim, Melbourne EpiCentre, The Royal Melbourne Hospital, Hospital Clínic de Barcelona (ICMiD), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Nepean Hospital, Ghent University Hospital, Universidad de Santiago de Chile [Santiago] (USACH), University of Sydney and Nepean Hospital, Hospital Tengku Ampuan Afzan (HTAA), Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), University Hospital of Ioannina, Royal Brisbane & Women's Hospital, Cliniques universitaires St Luc [Bruxelles], Guy's and St Thomas' Hospital [London], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Universitat Internacional de Catalunya [Barcelona] (UIC), St James's University Hospital, Leeds Teaching Hospitals NHS Trust, International Islamic University Malaysia [Kuala Lumpur], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), University of South Australia [Adelaide], Basil Hetzel Institute (BHI), Translational Research Institute (TRI), Gold Coast University Hospital, University Hospital of Tarragona 'Joan XXIII', University Rovirai Virgili de Tarragona (URV), Ochsner Medical Center, The Queen Elizabeth Hospital, Hospital Clínic de Barcelona, Roberts, Jason A., Joynt, Gavin M., Lee, Anna, Choi, Gordon, Roberts, Michael S., Sinnollareddy, Mahipal, and Lipman, Jeffrey

Subjects
0301 basic medicine, Continuous renal replacement therapy, medicine.medical_treatment, continuous renal replacement therapy, Antibiotics, urologic and male genital diseases, MESH: Meropenem, 030226 pharmacology & pharmacy, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, law, Prospective Studies, pharmacokinetic, extended daily dialysis, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Extended daily dialysis, Intensive care unit, Anti-Bacterial Agents, 3. Good health, Renal Replacement Therapy, Infectious Diseases, MESH: Critical Illness, Vancomycin, beta-lactam, medicine.drug, MESH: Piperacillin, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, Critical Illness, Beta-lactam, 030106 microbiology, Pharmacokinetic, Meropenem, 03 medical and health sciences, MESH: Anti-Bacterial Agents, Internal medicine, Intensive care, medicine, Humans, Trough Concentration, Dosing, Renal replacement therapy, Piperacillin, MESH: Humans, business.industry, MESH: Prospective Studies, renal clearance, MESH: Renal Replacement Therapy, business, Renal clearance
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.

Published
2020

3. The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: Data from the multinational SMARRT Study

Author

Roberts, Jason A, Joynt, Gavin, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra L, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João P, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, Cole, C Louise, Creteur, Jacques, De Waele, Jan J, Deans, Renae, Eastwood, Glenn M, Escobar, Leslie, Gomersall, Charles, Gresham, Rebecca, Jamal, Janattul Ain, Kluge, Stefan, König, Christina, Koulouras, Vasilios P, Lassig-Smith, Melissa, Laterre, Pierre-François, Lei, Katie, Leung, Patricia, Lefrant, Jean-Yves, Llauradó-Serra, Mireia, Martin-Loeches, Ignacio, Mat Nor, Mohd Basri, Ostermann, Marlies, Parker, Suzanne L, Rello, Jordi, Roberts, Darren M, Roberts, Michael S, Richards, Brent, Rodríguez, Alejandro, Roehr, Anka C, Roger, Claire, Seoane, Leonardo, Sinnollareddy, Mahipal, Sousa, Eduardo, Soy, Dolors, Spring, Anna, Starr, Therese, Thomas, Jane, Turnidge, John, Wallis, Steven C, Williams, Tricia, Wittebole, Xavier, Zikou, Xanthi T, Paul, Sanjoy, Lipman, Jeffrey, UCL - SSS/IREC/MEDA - Pôle de médecine aiguë, and UCL - (SLuc) Service de soins intensifs

Subjects
Continuous renal replacement therapy, Beta-lactam, Trough concentration, Pharmacokinetic, urologic and male genital diseases, Extended daily dialysis, Renal clearance
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 to relate observed trough antibiotic concentrations to optimal targets. METHODS: We performed a prospective, observational, multi-national, 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/min (interquartile range [IQR] 35-65) and higher eTRCL was associated with lower trough concentrations for all antibiotics (p

Published
2021

5. 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.

Author

Roberts, Jason A, Joynt, Gavin M, Lee, Anna, Choi, Gordon, Bellomo, Rinaldo, Kanji, Salmaan, Mudaliar, M Yugan, Peake, Sandra L, Stephens, Dianne, Taccone, Fabio Silvio, Ulldemolins, Marta, Valkonen, Miia Maaria, Agbeve, Julius, Baptista, João P, Bekos, Vasileios, Boidin, Clement, Brinkmann, Alexander, Buizen, Luke, Castro, Pedro, and Cole, C Louise

Subjects
THERAPEUTICS, MEROPENEM, SCIENTIFIC observation, BETA lactam antibiotics, CRITICALLY ill, PATIENTS, RENAL replacement therapy, VANCOMYCIN, PENICILLIN, AMPICILLIN, ANTIBIOTICS, LONGITUDINAL method
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. [ABSTRACT FROM AUTHOR]

Published
2021
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6. 610

Author

Lin, Hsin, primary, Boidin, Clement, additional, Evans, Danielle, additional, Lopez, Natasha, additional, Healy, Daniel, additional, Serpico, Elena, additional, Goutelle, Sylvain, additional, and Roberts, Jason, additional

Published
2019
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8. 610: OPTIMIZE CEFEPIME DOSING IN CRITICALLY ILL PATIENTS RECEIVING CONTINUOUS VENOVENOUS HEMOFILTRATION.

Author

Lin, Hsin, Boidin, Clement, Evans, Danielle, Lopez, Natasha, Healy, Daniel, Serpico, Elena, Goutelle, Sylvain, and Roberts, Jason

Subjects
*CEFEPIME, *CRITICALLY ill, *BLOOD filtration
Abstract

B Learning Objectives: b Cefepime pharmacokinetic (PK) in continuous veno-venous hemofiltration (CVVH) is applied extremely variably leading to a higher likelihood of ineffective or neurotoxic exposures. According to simulations, the most appropriate dosing regimen was continuous infusion of 2g/24h which had a 90% probability of achieving 100%fT>MIC at steady state with a toxic concentration risk <10%. [Extracted from the article]

Published
2019
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