Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy

Roberts, Jason A. and Ulldemolins, Marta and Liu, Xin and Baptista, João P. and Bilgrami, Irma and Boidin, Clement and Brinkmann, Alexander and Castro, Pedro and Choi, Gordon and Cole, Louise and Waele, Jan J. De and Deans, Renae and Donnellan, Sine and Eastwood, Glenn M. and Frey, Otto R. and Goutelle, Sylvain and Gresham, Rebecca and Jamal, Janattul AIn and Joynt, Gavin M. and Kanji, Salmaan and Kluge, Stefan and König, Christina and Koulouras, Vasilios P and Lassig-Smith, Melissa and Laterre, Pierre-Francois and Lee, Anna and Lefran, Jean‑Yves and Lei, Katie and Leung, Patricia and Llauradó-Serra, Mireia and Martin-Loeches, Ignacio and Mat Nor, Mohd Basri and Shee, Yugang and Ostermann, Marlies and Paul, Sanjoy K and Peake, Sandra L and Rello, Jordi and Roberts, Darren M. and Roberts, Michael S. and Doberstein, 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 Stephens, Dianne and Taccone, Fabio Silvio and Thomas, Jane and Turnidge, John and Valkonen, Miia and Varghese, Julie M. and Wallis, Steven C and Walker, Robert J. and Williams, Tricia and Wilson, Luke C. and Wittebole, Xavier and Wright, Daniel F. and Zikou, Xanthi T and Bellomo,, Rinaldo and Lipman, Jeffrey (2025) Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy. Intensive Care Medicine, 51 (-). pp. 1628-1640. ISSN 0342-4642 E-ISSN 1432-1238

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Abstract

Purpose: Optimal dosing of meropenem and piperacillin/tazobactam in critically ill patients receiving renal replacement therapy (RRT) is uncertain due to variable pharmacokinetics. We aimed to develop generalisable optimised dosing recommendations for these antibiotics. Methods: Prospective, multinational pharmacokinetic study including patients requiring various forms of RRT. Independent population PK models were developed, externally validated and applied to perform Monte Carlo dosing simulations using Monolix and Simulx. We calculated the probability that these dosing regimens achieved standard and high therapeutic unbound antibiotic concentrations over 100% of the dosing interval for the treatment of Enterobacterales and Pseudomonas aeruginosa. Results: We enrolled 300 patients from 22 intensive care units across 12 countries receiving continuous veno-venous haemodialysis (13.0%), haemofiltration (23.3%), haemodiafiltration (48.4%) or sustained low-efficiency dialysis (15.3%). Models were developed using data from 234 patients (8322 samples) and validated with 66 additional patients (560 samples). Predictive performance was high, with mean prediction errors of − 5.2% for meropenem and − 16.9% for piperacillin. Dosing simulations showed that meropenem and piperacillin/tazobactam dosing requirements were dependent on urine output and RRT intensity and duration (p < 0.05). In all scenarios, extended/continuous infusions led to a better achievement of effective concentrations with lower daily doses compared to short infusion. Dosing nomograms were developed to inform dosing for different RRT settings, urine outputs, and target concentrations. Conclusion: RRT intensity and duration and urine output determine meropenem and piperacillin/tazobactam dosing requirements in critically ill patients receiving RRT. Extended/continuous infusions facilitate the attainment of effective concentrations.

Item Type:	Article (Journal)
Uncontrolled Keywords:	Critically ill patients, Meropenem, Piperacillin/tazobactam, Renal replacement therapy, Pharmacokinetics, Dosing nomograms
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 Kulliyyah of Medicine > Department of Anaesthesiology & Intensive Care
Depositing User:	Dr. Mohd Basri Mat Nor
Date Deposited:	03 Feb 2026 16:55
Last Modified:	03 Feb 2026 16:55
Queue Number:	2026-01-Q1989
URI:	http://irep.iium.edu.my/id/eprint/127009

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