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

Jason A. Roberts, Gavin M. 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 ColeJacques 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 K. Paul, Jeffrey Lipman, SMARRT Study Collaborators and the ANZICS Clinical Trials Group

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20 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1369-1378
Number of pages10
JournalClinical Infectious Diseases
Volume72
Issue number8
DOIs
Publication statusPublished - 15 Apr 2021

Keywords

  • beta-lactam
  • continuous renal replacement therapy
  • extended daily dialysis
  • pharmacokinetic
  • renal clearance

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