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
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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.

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.

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.

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.
Acceptance Date03/03/2020
All Author(s) ListJason A Roberts, Gavin Joynt, Anna Lee, Gordon Choi, Rinaldo Bellomo, Salmaan Kanji, M Yugan Mudaliar, Sandra L Peake, Dianne Stephens, Fabio Silvio Taccone, Marta Ulldemolins, Miia Maaria Valkonen, Julius Agbeve, João P Baptista, Vasileios Bekos, Clement Boidin, Alexander Brinkmann, Luke Buizen, Pedro Castro, C Louise Cole, Jacques Creteur, Jan J De Waele, Renae Deans, Glenn M Eastwood, Leslie Escobar, Charles Gomersall, Rebecca Gresham, Janattul Ain Jamal, Stefan Kluge, Christina König, Vasilios P Koulouras, Melissa Lassig-Smith, Pierre-Francois Laterre, Katie Lei, Patricia Leung, Jean-Yves Lefrant, Mireia Llauradó-Serra, Ignacio Martin-Loeches, Mohd Basri Mat Nor, Marlies Ostermann, Suzanne L Parker, Jordi Rello, Darren M Roberts, Michael S Roberts, Brent Richards, Alejandro Rodríguez, Anka C Roehr, Claire Roger, Leonardo Seoane, Mahipal Sinnollareddy, Eduardo Sousa, Dolors Soy, Anna Spring, Therese Starr, Jane Thomas, John Turnidge, Steven C Wallis, Tricia Williams, Xavier Wittebole, Xanthi T Zikou, Sanjoy Paul, Jeffrey Lipman; on behalf of the SMARRT Study Collaborators and the ANZICS Clinical Trials Group
Journal nameClinical Infectious Diseases
Volume Number72
Issue Number8
PublisherOxford University Press
Pages1369 - 1378
LanguagesEnglish-United States
Keywordspharmacokinetic, trough concentration, continuous renal replacement therapy, extended daily dialysis, beta-lactam, renal clearance

Last updated on 2021-17-09 at 00:53