Scientific Poster Session II - Original Research

Original Research
  Sunday, October 13, 2024
  12:45 PM–02:15 PM

Abstract

Introduction: Cefiderocol is used to treat multidrug-resistant gram-negative bacterial infections which are common in critically ill patients. Attaining adequate drug levels is crucial for successful treatment. While dosing guidelines exist for cefiderocol for other kidney replacement therapies, data is limited for prolonged intermittent kidney replacement therapy (PIKRT).

Research Question or Hypothesis: What are the optimal cefiderocol dosing regimens for critically ill patients receiving PIKRT?

Study Design: In-silico study using a Monte Carlo simulation (MCS)

Methods: Using relevant demographic and pharmacokinetic data, a one-compartment pharmacokinetic model was developed for anuric patients undergoing 8 or 10 hour PIKRT. Monte Carlo Simulations (MCS) were utilized to determine the probability of target attainment (PTA) for various cefiderocol doses administered inter-PIKRT or post-PIKRT in 5,000 virtual patients for 48 hours. The pharmacokinetic/pharmacodynamic target was 75% time of free plasma concentration above the minimum inhibitory concentration (75% fT>1xMIC) of 4 mg/L assuming P. aeruginosa or Enterobacterales. Additionally, more aggressive targets of 100% fT>1xMIC or 75% fT>4xMIC were evaluated. Doses attaining 90% PTA were considered optimal. Eight doses were tested (500mg q8h, 750mg q8h, 1000mg q8h, 1500mg q8h, 750mg q12h, 1000mg q12h, 1500mg q12h, 2000 mg q12h).

Results: All tested cefiderocol dosing regimens regardless of drug administration and timing of PIKRT achieved a PTA>90% for the goal of 75% fT>1xMIC. No dosing regimens reached a PTA>90% for 100% fT>1xMIC. Only 1500mg q8h achieved a PTA>90% for the target of 75% fT>4xMIC.

Conclusion: The overall recommendation for cefiderocol dosing in 8 or 10-hour PIKRT would be 750mg q12h. If a more aggressive efficacy target is warranted,1500mg q8h would be appropriate. These findings need clinical validation.

Presenting Author

Susan Lewis PharmD
University of Findlay College of Pharmacy

Authors

Elizabeth Bockey PharmD (Anticipated 2026)
The University of Findlay

Madeline Deiderick PharmD (Anticipated 2026)
The University of Findlay

Jacob Holmes PharmD (Anticipated 2026)
The University of Findlay

Sydnee Payer PharmD (Anticipated 2026)
The University of Findlay

Sierra Shoemaker PharmD (Anticipated 2026)
The University of Findlay