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Abstract: PO0252

Optimal Cefepime Dosing Regimens in Obese Critically Ill Patients with AKI Receiving Continuous Renal Replacement Therapy

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Rungkitwattanakul, Dhakrit "Jesse", Howard University College of Pharmacy, Washington, District of Columbia, United States
  • Yabusaki, Andrew A., Howard University College of Pharmacy, Washington, District of Columbia, United States
  • Hsiao, Kuang-Heng, Howard University College of Pharmacy, Washington, District of Columbia, United States
  • Getaw, Kendra, Howard University College of Pharmacy, Washington, District of Columbia, United States
  • Charoensareerat, Taniya, Siam University, Bangkok, Bangkok, Thailand
  • Chaijamorn, Weerachai, Siam University, Bangkok, Bangkok, Thailand
Background

Cefepime can be removed by continuous renal replacement therapy (CRRT) due to its pharmacokinetics. Physiologic alterations in obesity and critical illness commonly impact the pharmacokinetics of antibiotics and may result in suboptimal dosing. The information regarding drug dosing in this population is relatively limited. The objective of our study is to determine the appropriate dosing of cefepime in obese critically ill patients receiving continuous renal replacement therapy (CRRT).

Methods

All necessary pharmacokinetic and pharmacodynamic parameters from obese critically ill patients were obtained to develop one-compartment mathematical models with first-order elimination. Obesity is defined as a body mass index (BMI) greater than 30 kg/m2 according to WHO classification. Cefepime concentration-time profiles were calculated to determine the efficacy based on the probability of target attainment (PTA) of both pharmacodynamics targets of 70% T> MIC and 70% T> 4MIC for Gram-negative infections. A group of 10,000 virtual patients was simulated and tested using Monte Carlo simulations for each dose in the models. The optimal dosing regimens or the “successful dose” were defined as the lowest daily dose that achieved target PTA in at least 90% of the virtual patients.

Results

Our results showed the highest FDA-recommended dosing of cefepime at 2000 mg every 8 hours for patients receiving CRRT with an effluent rate of 25 mL/kg/h cannot achieve at least 90% of PTA for Gram-negative infection due to pseudomonas aeruginosa with an MIC of 8 mg/L. In addition, when a higher effluent rate of 35 mL/kg/h and an aggressive pharmacodynamic targets were applied, the % PTA decreased. The successful dose (3000 mg loading dose on day 1 followed by 2500 mg every 8 hours) was far exceeded the maximal FDA-approved doses.

Conclusion

Using cefepime in obese critically ill AKI patients receiving CRRT with traditional dosing of 2000 mg every 8 hours cannot be recommended as an empiric therapy due to suboptimal efficacy. The MIC target and replacement fluid rate directly impact the pharmacodynamic outcome.