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 Article

Full Text via DOI: 10.1093/cid/ciaa224 Web of Science: 000646249200011
Highly Cited Paper International Collaboration

Cited authors

  • Roberts JA, Joynt GM, Lee A, Choi G, Bellomo R, Kanji S, Mudaliar MY, Peake SL, Stephens D, Taccone FS, Ulldemolins M, Valkonen MM, Agbeve J, Baptista JP, Bekos V, Boidin C, Brinkmann A, Buizen L, Castro P, Cole CL, Creteur J, De Waele JJ, Deans R, Eastwood GM, Escobar L, Gomersall C, Gresham R, Jamal JA, Kluge S, Konig C, Koulouras VP, Lassig-Smith M, Laterre PF, Lei KT, Leung P, Lefrant JY, Llaurado-Serra M, Martin-Loeches I, Nor MBM, Ostermann M, Parker SL, Rello J, Roberts DM, Roberts MS, Richards B, Rodriguez A, Roehr AC, Roger C, Seoane L, Sinnollareddy M, Sousa E, Soy D, Spring A, Starr T, Thomas J, Turnidge J, Wallis SC, Williams T, Wittebole X, Zikou XT, Paul SK, Lipman J

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.

Authors

Publication date

  • 2021

Published in

International Standard Serial Number (ISSN)

  • 1058-4838

Number of pages

  • 10

Start page

  • 1369

End page

  • 1378

Volume

  • 72

Issue

  • 8