TY - JOUR
T1 - The Effect of Renal Replacement Therapy and Antibiotic Dose on Antibiotic Concentrations in Critically Ill Patients
T2 - Data from the Multinational Sampling Antibiotics in Renal Replacement Therapy Study
AU - Roberts, Jason A.
AU - Joynt, Gavin M.
AU - Lee, Anna
AU - Choi, Gordon
AU - Bellomo, Rinaldo
AU - Kanji, Salmaan
AU - Mudaliar, M. Yugan
AU - Peake, Sandra L.
AU - Stephens, DIanne
AU - Taccone, Fabio Silvio
AU - Ulldemolins, Marta
AU - Valkonen, Miia Maaria
AU - Agbeve, Julius
AU - Baptista, João P.
AU - Bekos, Vasileios
AU - Boidin, Clement
AU - Brinkmann, Alexander
AU - Buizen, Luke
AU - Castro, Pedro
AU - Cole, C. Louise
AU - Creteur, Jacques
AU - De Waele, Jan J.
AU - Deans, Renae
AU - Eastwood, Glenn M.
AU - Escobar, Leslie
AU - Gomersall, Charles
AU - Gresham, Rebecca
AU - Jamal, Janattul Ain
AU - Kluge, Stefan
AU - König, Christina
AU - Koulouras, Vasilios P.
AU - Lassig-Smith, Melissa
AU - Laterre, Pierre Francois
AU - Lei, Katie
AU - Leung, Patricia
AU - Lefrant, Jean Yves
AU - Llauradó-Serra, Mireia
AU - Martin-Loeches, Ignacio
AU - Mat Nor, Mohd Basri
AU - Ostermann, Marlies
AU - Parker, Suzanne L.
AU - Rello, Jordi
AU - Roberts, Darren M.
AU - Roberts, Michael S.
AU - Richards, Brent
AU - Rodríguez, Alejandro
AU - Roehr, Anka C.
AU - Roger, Claire
AU - Seoane, Leonardo
AU - Sinnollareddy, Mahipal
AU - Sousa, Eduardo
AU - Soy, Dolors
AU - Spring, Anna
AU - Starr, Therese
AU - Thomas, Jane
AU - Turnidge, John
AU - Wallis, Steven C.
AU - Williams, Tricia
AU - Wittebole, Xavier
AU - Zikou, Xanthi T.
AU - Paul, Sanjoy K.
AU - Lipman, Jeffrey
AU - Andresen, Max
AU - Baltazar, Sónia F.
AU - Barbar, Saber
AU - Costa, Eulália
AU - Durand, Dominique
AU - Freitas, Ricardo
AU - Frey, Otto R.
AU - Guerra Valero, Yarmarly
AU - Haughton, Margaret
AU - Koeberer, Andreas
AU - Kollef, Marin
AU - Klein, Kerenaftali
AU - Mehta, Ravindra
AU - McKenzie, Cathy
AU - Muller, Laurent
AU - Nair, Priya
AU - Nayyar, Vineet
AU - Ordóñez Mejia, Jenny L.
AU - Panagou, Georgia Laura
AU - Paxton, Jody
AU - Peck, Leah
AU - Samanta, Mayukh
AU - Vincent, Jean Louise
AU - Wan, Ruth
AU - Young, Helen
N1 - Funding Information:
Financial support. This work was supported by funding from the National Health and Medical Research Council (project grant APP1044941), the Centre for Research Excellence (grant APP1099452), and a Practitioner Fellowship to J. A. R., (grant APP1117065). Partial support was provided by a grant from the Research Grants Council of the Hong Kong Special Administrative Region, China (project number CUHK 14106614). Support was also provided by the Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) initiative through Therapeutic Innovation Australia (to S. K. P).
Funding Information:
Potential conflicts of interest. A. B. declares unrelated travel grants and lecture fees from Fresenius Medical Care and personal fees from Grünenthal GmbH, Merck Sharp & Dohme (MSD) GmbH, Pfizer Pharma GmbH, Niedersächsisches Landesgesundheitsamt, LADR-Laboratory Bremen, Laborbetriebsgesellschaft Dr Dirkes-Kersting GmbH, Gelsenkirchen, Laboratory Volkmann, Karlsruhe, Ecomed-Storck GmbH, Elsevier GmbH, Springer-Verlag, and Bayerische Landesärztekammer. R. B. reports institutional grants and personal fees from Baxter and BBraun. B. C. reports personal fees from the European Society of Clinical Microbiology and Infectious Diseases – the European Congress of Clinical Microbiology and Infectious Diseases (ESCMID-ECCMID). J. A. R. reports board membership payments from Infectopharm and MSD; institutional grants from MSD, Cardeas Pharmaceuticals, and QPEX; and lecture fees from MSD and Pfizer. J. J. D. W. reports being a Senior Clinical Investigator of the Research Foundation–Flanders (Belgium), and institutional grants from Bayer, Pfizer, MSD, Grifols, and Accelerate. C. G. reports department funding to support educational activities from Pfizer, Astellas, and MSD. P.-F. L. reports personal fees from Inotrem and Adrenomed. J. L. reports personal fees from MSD and Pfizer. M. S. R. reports personal fees from Quality Medication Care, Glaxo Smith Kline, University of Queensland & University of South Australia, SPIE Photonics West & Advanced Imaging Methods, and SF and institutional grants from the US Food and Drug Administration. I. M.-L. reports personal fees from MSD and Gilead. M. O. reports grants from Fresenius Medical and speaking honoraria from Fresenius Medical and Baxter. L. S. reports grants from Patient-Centered Outcomes Research Institute (PCORI). E. S. reports personal fees from Baxter. S. C. W. reports institutional grants from the National Health and Medical Research Council. S. L. P. reports an Early Career Research Fellowship funding from the Australian National Health and Medical Research Council (grant APP1142757). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
Publisher Copyright:
© 2020
PY - 2021/4/15
Y1 - 2021/4/15
N2 - 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.
AB - 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.
KW - beta-lactam
KW - continuous renal replacement therapy
KW - extended daily dialysis
KW - pharmacokinetic
KW - renal clearance
UR - http://www.scopus.com/inward/record.url?scp=85105765911&partnerID=8YFLogxK
U2 - 10.1093/cid/ciaa224
DO - 10.1093/cid/ciaa224
M3 - Article
C2 - 32150603
AN - SCOPUS:85105765911
SN - 1058-4838
VL - 72
SP - 1369
EP - 1378
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 8
ER -