In this episode, I’ll discuss the optimal dosing regimen for meropenem and piperacillin/tazobactam in critically ill patients receiving continuous renal replacement therapy.
Achieving adequate antibiotic concentrations over 100% of the dosing interval is particularly challenging for critically ill patients receiving continuous renal replacement therapy.
A group of authors recently published in Intensive Care Medicine the results of a prospective, multinational pharmacokinetic study including critically ill patients requiring various forms of RRT that uses Monte Carlo simulations to determine the ideal dosing regimen for meropenem and piperacillin/tazobactam.
Data from 300 patients were divided into a derivation and a validation cohort. Dosing simulations using Monte Carlo analysis were performed for different short, extended, and continuous infusion regimens that are commonly used in ICU practice. In all simulations, the first simulated dose was always a 30 minute short infusion. For both antibiotics, a continuous infusion performed best at achieving 100% of the dosing interval above MIC without exceeding toxic ranges. The models developed and validated using this data had low mean prediction errors, indicating that they possess high predictive performance.
The authors developed a dosing nomogram for a standard target and high target concentration for both Enterobacterales and Pseudomonas. For patients receiving continuous RRT, the intensity (calculated as dialysate + replacement fluid flow rates) determines whether a dose escalation is needed with cutoff points at 1.5 L/h, 2.5 L/h, and 3.5L/h. In addition, since the authors also found that dosing requirements were dependent on urine output, the nomograms also categorize dose recommendations based on these factors. The cutoff point for dose escalation based on urine output is determined by the total urine output in the past 24 hours and is 500 mL or more in the last 24 hours for meropenem and 100 mL or more in the last 24 hours for piperacillin/tazobactam.
For meropenem, the ideal continuous infusion dose ranged from 1 to 3 grams per 24 hours, depending on the target concentration, RRT intensity, and residual urine output. For piperacillin/tazobactam, the ideal continuous infusion dose based on the same factors ranged from 6 to 12 grams of piperacillin per 24 hours.
The authors include a very easy-to-read table for meropenem and piperacillin/tazobactam. In addition to nomograms for continuous RRT, these tables include nomograms for intermittent sustained low-efficiency dialysis (SLED) at various durations.
The authors recommend titrating the dose of antibiotic daily using the nomogram and changes to urine output and RRT intensity.
The article in this episode is a selection from my Hospital Pharmacy Academy’s weekly literature digest. Have you ever felt like your physician colleagues are one step ahead of you with new literature developments? Every week, Academy members are provided a summary curated and explained by me of the top hospital pharmacy-related articles published that week from over 20 major journals and sources to save you time and keep you up to date with the literature. To get immediate access, go to pharmacyjoe.com/academy.
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