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
Authors: Roberts Jason A , Joynt Gavin M , 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 K , Lipman Jeffrey ,   SMARRT Study Collaborators and the ANZICS Clinical Trials Group, Andresen Max , Baltazar Sónia F , Barbar Saber , Costa Eulália , Durand Dominique , Freitas Ricardo , Frey Otto R , Guerra Valero Yarmarly , Haughton Margaret , Koeberer Andreas , Kollef Marin , Klein Kerenaftali , Mehta Ravindra , McKenzie Cathy , Muller Laurent , Nair Priya , Nayyar Vineet , Ordóñez Mejia Jenny L , Panagou Georgia-Laura , Paxton Jody , Peck Leah , Samanta Mayukh , Vincent Jean-Louise , Wan Ruth , Young Helen 
Published: March 2020

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 &lt; .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.