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

TY - JOUR

T1 - The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: Data from the multinational SMARRT Study

AU - Roberts, Jason A

AU - Joynt, Gavin

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

AU - Lipman, Jeffrey

AU - SMARRT Study Collaborators and the ANZICS Clinical Trials Group

N1 - © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

PY - 2021/4/26

Y1 - 2021/4/26

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 - Anti-Bacterial Agents/therapeutic use

KW - Critical Illness

KW - Humans

KW - Meropenem

KW - Piperacillin

KW - Prospective Studies

KW - Renal Replacement Therapy

U2 - 10.1093/cid/ciaa224

DO - 10.1093/cid/ciaa224

M3 - SCORING: Journal article

C2 - 32150603

VL - 72

SP - 1369

EP - 1378

JO - CLIN INFECT DIS

JF - CLIN INFECT DIS

SN - 1058-4838

IS - 8

ER -