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 - on behalf of the SMARRT Study Collaborators and the ANZICS Clinical Trials Group
N1 - Publisher Copyright:
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].
Copyright:
This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
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 -
