Cefepime dosing regimens in critically ill patients receiving continuous renal replacement therapy: A Monte Carlo simulation study

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Research Article: Cefepime dosing regimens in critically ill patients receiving continuous renal replacement therapy: A Monte Carlo simulation study
Author: Weerachai Chaijamorn, Taniya Charoensareerat, Nattachai Srisawat, Sutthiporn Pattharachayakul and Apinya Boonpeng
Email: weerachai.cha@siam.edu
Department|Faculty: Faculty of Pharmacy,  Siam University, Bangkok 10160
Published: Journal of Intensive Care

Citation

Weerachai Chaijamorn, Taniya Charoensareerat, Nattachai Srisawat, Sutthiporn Pattharachayakul and Apinya Boonpeng. (2018). Cefepime dosing regimens in critically ill patients receiving continuous renal replacement therapy: A Monte Carlo simulation study.  Journal of Intensive Care, Retrieved from https://doi.org/10.1186/s40560-018-0330-8/


ABSTRACT

Background
Cefepime can be removed by continuous renal replacement therapy (CRRT) due to its pharmacokinetics. The purpose of this study is to define the optimal cefepime dosing regimens for critically ill patients receiving CRRT using Monte Carlo simulations (MCS).

Methods
The CRRT models of cefepime disposition during 48 h with different effluent rates were developed using published pharmacokinetic parameters, patient demographic data, and CRRT settings. Pharmacodynamic target was the cumulative percentage of a 48-h period of at least 70% that free cefepime concentration exceeds the four times susceptible breakpoint of Pseudomonas aeruginosa (minimum inhibitory concentration, MIC of 8). All recommended dosing regimens from available clinical resources were evaluated for the probability of target attainment (PTA) using MCS to generate drug disposition in a group of 5000 virtual patients for each dose. The optimal doses were defined as achieving the PTA at least 90% of virtual patients with lowest daily doses and the acceptable risk of neurotoxicity.

Results
Optimal cefepime doses in critically ill patients receiving CRRT with Kidney Disease: Improving Global Outcomes (KDIGO) recommended effluent rates were a regimen of 2 g loading dose followed by 1.5–1.75 g every 8 h for Gram-negative infections with a neurotoxicity risk of < 17%. Cefepime dosing regimens from this study were considerably higher than the recommended doses from clinical resources.

Conclusion
All recommended dosing regimens for patients receiving CRRT from available clinical resources failed to achieve the PTA target. The optimal dosing regimens were suggested based on CRRT modalities, MIC values, and different effluent rates. Clinical validation is warranted.

Keywords: Cefepime, Dosing, Pharmacokinetics, Pharmacodynamics, Continuous renal replacement therapy, Critically ill patients.


Cefepime dosing regimens in critically ill patients receiving continuous renal replacement therapy: a Monte Carlo simulation study

Faculty of Pharmacy, Siam University, Bangkok, Thailand

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