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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

2020; Oxford University Press; Volume: 72; Issue: 8 Linguagem: Inglês

10.1093/cid/ciaa224

1537-6591

Jason A. Roberts, Gavin M. Joynt, Anna Lee, Gordon Choi, Rinaldo Bellomo, Salmaan Kanji, M. Y. Mudaliar, Sandra Peake, Dianne Stephens, Fabio Silvio Taccone, Marta Ulldemolins, Miia Valkonen, Julius Agbeve, João Pedro Baptista, Vasileios Bekos, Clément Boidin, Alexander Brinkmann, Luke Buizen, Pedro Castro, Caroline Cole, Jacques Créteur, Jan J. De Waele, Renae Deans, Glenn M. Eastwood, Leslie Escobar, Charles D. Gomersall, Rebecca Gresham, Janattul‐Ain Jamal, Stefan Kluge, Christina König, Vasilios Koulouras, Melissa Lassig‐Smith, Pierre‐François Laterre, Katie Lei, Patricia Leung, Jean‐Yves Lefrant, Mireia Llauradó‐Serra, Ignacio Martín‐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 S. Williams, Xavier Wittebole, Xanthi Zikou, Sanjoy K. Paul, Jeffrey Lipman, Max Andresen, Sónia F Baltazar, Saber Davide Barbar, Eulália Costa, D. Durand, Ricardo Freitas, Otto Frey, Yarmarly C. Guerra Valero, Margaret Haughton, Andreas Koeberer, Marin H. Kollef, Kerenaftali Klein, Ravindra L. Mehta, Catherine McKenzie, Laurent Müller, Priya Nair, Vineet Nayyar, Jenny Lisette Ordóñez Mejia, Georgia-Laura Panagou, Jody Paxton, Leah Peck, Mayukh Samanta, Jean‐Louis Vincent, Ruth Wan, Helen Young,

Acute Kidney Injury Research

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 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.