Original Research
Saturday, October 12, 2024
11:30 AM–01:00 PM
Abstract
Introduction: Ceftolozane/tazobactam is a preferred agent to treat multi-drug resistant
Pseudomonas aeruginosa. Paucity of data exists to guide ceftolozane/tazobactam dosing regimens in critically ill patients receiving continuous venovenous hemofiltration (CVVH).
Research Question or Hypothesis: What are the ceftolozane/tazobactam doses attaining the pharmacodynamic targets in critically ill patients receiving CVVH with different effluent rates?
Study Design: Prospective in-silico study using Monte Carlo simulation (MCS)
Methods: Relevant published pharmacokinetic data was utilized to develop mathematical models to predict ceftolozane/tazobactam disposition in 5,000 virtual patients receiving CVVH with three effluent flow rates (Qf) of 20, 30, and 40 mL/kg/hr). Four conventional ceftolozane/tazobactam dosing regimens administered over 3 hours (e.g. 750mg loading dose (LD), 150mg q8h; 750mg LD, 375mg q8h; 750mg LD, 450mg q8h; 3g LD, 3g q8h) were simulated to evaluate the probability of target attainment (PTA). The pharmacodynamic targets used for ceftolozane was 40%, 60%, and 100% free serum concentrations above the minimum inhibitory concentration (fT>MIC) with an MIC of 4 mg/L assuming P. aeruginosa infection. Tazobactam target was 20% fT> minimum effective concentration of 1 mg/L. Optimal dosing regimens had a PTA of =90% during the initial 48 hours of therapy.
Results: For a 40% fT>MIC target, ceftozozane/tazobactam 750mg LD, then 150mg q8h was optimal at Qf of 20 mg/kg/hr and 750mg LD, then 375 mg q8h at Qf of 30-40 ml/kg/hr. For the target of 60% fT>MIC, 750mg LD, then 375mg q8h was necessary at Qf of 20-30 mL/kg/hr, and 750mg LD, then 450mg q8h at Qf of 40 ml/kg/hr. Achieving the aggressive target of 100% fT>MIC required 3g LD, then 3g q8h across all tested Qf settings.
Conclusion: MCS effectively predicted ceftolozane/tazobactam dosing regimens attaining different efficacy targets in patients undergoing CVVH at varying Qf rates. These findings can assist clinicians in making informed dosing decisions. However, clinical validation is warranted to confirm these results.
Presenting Author
Susan Lewis PharmD (Anticipated 2026)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
Susan Lewis PharmD
University of Findlay College of Pharmacy
Sydnee Payer PharmD (Anticipated 2026)
The University of Findlay
Sierra Shoemaker PharmD (Anticipated 2026)
The University of Findlay