Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy
Authors' 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.
Study context
- Population
- Critically ill patients receiving renal replacement therapy (RRT) (CVVHD, haemofiltration, haemodiafiltration or sustained low-efficiency dialysis) in 22 ICUs across 12 countries
- Participants
- 300 patients · 22 ICUs · 12 countries
- Exposure
- Extended/continuous infusion vs Short infusion
- Outcome
- Probability of achieving standard and high therapeutic unbound antibiotic concentrations over 100% of the dosing interval (Enterobacterales and Pseudomonas aeruginosa)
Methodological detailspopulation PK modelling, external validation, Monte Carlo dosing simulations, Dosing nomograms developed for different RRT settings, urine outputs and target concentrations
- Population PK modelling
- External validation
- Monte Carlo dosing simulations
- Dosing nomograms developed for different RRT settings, urine outputs and target concentrations
Main finding
As reported in the abstract
Determinants of dosing requirements and target attainment
- Meropenem and piperacillin/tazobactam dosing requirements dependent on urine output and RRT intensity and duration
- p < 0.05
Observational data: associations, not effects.
Further findings
RRT modality distribution
- Continuous veno-venous haemodialysis
- 13.0%
- Haemofiltration
- 23.3%
- Haemodiafiltration
- 48.4%
- Sustained low-efficiency dialysis
- 15.3%
Model predictive performance (mean prediction error)
- Meropenem
- - 5.2%
- Piperacillin
- - 16.9%
- Development 234 patients (8322 samples); validation 66 patients (560 samples)
Original publication
Meropenem and piperacillin/tazobactam optimised dosing regimens for critically ill patients receiving renal replacement therapy. Intensive Care Med. Published 13 August 2025. doi:10.
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