Impact of continuous renal replacement therapy and Cytosorb on cefiderocol pharmacokinetics: "One size does not fit all"

Abstract

Cefiderocol, a novel broad-spectrum cephalosporin, exhibits promising efficacy against carbapenem-resistant Gram-negative bacteria via a "Trojan horse" mechanism. Its pharmacokinetics (PK) and pharmacodynamics (PD) in critically ill patients, particularly under extracorporeal therapies such as Continuous Renal Replacement Therapy (CRRT) and hemoadsorption (HA), remain underexplored. This case report evaluates the PK/PD profile of cefiderocol in a 16-year-old male with relapsed B-cell leukemia, multi-organ failure, and septic shock treated with Continuous Venous-Venous Hemodiafiltration (CVVHDF) and Cytosorb® HA. Cefiderocol clearance and drug removal were monitored using Therapeutic Drug Monitoring (TDM). Data demonstrated that cefiderocol was susceptible to removal during CVVHDF and HA, with variable clearance rates and removal percentages across time points. HA displayed significant cefiderocol removal during the initial 120-180 min, tapering thereafter, while CVVHDF exhibited a fluctuating clearance pattern influenced by effluent rates. Despite achieving PK/PD efficacy targets (C_min/MIC ⩾ 4) in 71.4% of cases, variability was observed. Findings highlight the need for personalized antibiotic dosing in critically ill patients undergoing extracorporeal therapies. Adjustments such as additional dosing during early HA or extended cefiderocol infusion (2-3 h) at shorter intervals (every 6 h) may optimize therapeutic outcomes. These insights underscore the critical role of TDM in ensuring effective PK/PD target attainment, though further research is required to substantiate these preliminary observations.

Keywords: CytoSorb; PK/PD; antibiotics; cefiderocol; extra-corporeal therapies; hemoadsorption; septic shock; therapeutic drug monitoring.