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Title: The effect of renal replacement therapy and antibiotic dose on antibiotic concentrations in critically ill patients: Data from the multinational SMARRT Study.
Authors: 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-Francois
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
Citation: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2020-03-09
Abstract: 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. 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. 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<0.05). The median (IQR) trough concentration for meropenem was 12.1 mg/L (7.9-18.8), piperacillin 78.6 mg/L (49.5-127.3), tazobactam 9.5 mg/L (6.3-14.2) and vancomycin 14.3 mg/L (11.6-21.8). Trough concentrations failed to meet optimal higher limits in 26%, 36%, 72%, and optimal lower limits in 4%, 4%, and 55% of patients for meropenem, piperacillin and vancomycin respectively. 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.
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Journal title: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
Publication Date: 2020-03-09
Type: Journal Article
DOI: 10.1093/cid/ciaa224
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