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

Roberts, Jason A. and Joynt, Gavin M. and Lee, Anna and Choi, Gordon and Bellomo,, Rinaldo and Kanji, Salmaan and Mudaliar, M Yugan and Peake, Sandra L and Stephens, Dianne and Taccone, Fabio Silvio and Ulldemolins, Marta and Valkonen, Miia Maaria and Agbeve, Julius and Baptista, João P and Bekos, Vasileios and Boidin, Clement and Brinkmann, Alexander and Buizen, Luke and Castro, Pedro and Cole, C Louise and Creteur, Jacques and Waele, Jan J De and Deans, Renae and Eastwood, Glenn M and Escobar, Leslie and Gomersall, Charles and Gresham, Rebecca and Jamal, Janattul Ain and Kluge, Stefan and König, Christina and Koulouras, Vasilios P and Lassig-Smith, Melissa and Laterre, Pierre-Francois and Lei, Katie and Leung, Patricia and Lefrant, Jean-Yves and Llauradó-Serra, Mireia and Martin-Loeches, Ignacio and Mat Nor, Mohd Basri and Ostermann, Marlies and Parker, Suzanne L and Rello, Jordi and Roberts, Darren M and Roberts, Michael S and Richards, Brent and Rodríguez, Alejandro and Roehr, Anka C and Roger, Claire and Seoane, Leonardo and Sinnollareddy, Mahipal and Sousa, Eduardo and Soy, Dolors and Spring, Anna and Starr, Therese and Thomas, Jane and Turnidge, John and Wallis, Steven C and Williams, Tricia and Wittebole, Xavier and Zikou, Xanthi T and Paul, Sanjoy K and Lipman, Jeffrey (2020) 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. Clinical Infectious Disease. pp. 1-32. ISSN 1058-4838 E-ISSN 1537-6591 (In Press)

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Abstract

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 to relate observed trough antibiotic concentrations to optimal targets. Methods: 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. 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/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. 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.

Item Type:	Article (Journal)
Additional Information:	5608/81770
Uncontrolled Keywords:	pharmacokinetic, continuous renal replacement therapy, extended daily dialysis, beta-lactam, renal clearance
Subjects:	R Medicine > RC Internal medicine > RC82 Medical Emergencies, Critical Care, Intensive Care, First Aid
Kulliyyahs/Centres/Divisions/Institutes (Can select more than one option. Press CONTROL button):	Kulliyyah of Medicine > Department of Anaesthesiology & Intensive Care
Depositing User:	Dr. Mohd Basri Mat Nor
Date Deposited:	05 Aug 2020 11:50
Last Modified:	24 Nov 2020 12:15
URI:	http://irep.iium.edu.my/id/eprint/81770

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