Pharmacokinetics/pharmacodynamics of cefiderocol administered by continuous infusion in a case series of critically ill patients with carbapenem-resistant Acinetobacter baumannii infections undergoing continuous venovenous haemodiafiltration (CVVHDF)

Objectives: To assess the pharmacokinetics/pharmacodynamics (PK/PD) of cefiderocol administered by continuous infusion (CI) in a case series of critically ill patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections undergoing continuous venovenous haemodiafiltration (CVVHDF). Methods: Critically ill patients receiving CI cefiderocol during CVVHDF for documented bloodstream infections (BSIs), ventilator-associated pneumonia (VAP), and/or complicated intrabdominal infections (cIAIs) caused by CRAB and undergoing therapeutic drug monitoring (TDM) from February 2022 to January 2023 were retrospectively assessed. Cefiderocol concentrations were determined at steady-state, and the free fraction (fCss) was calculated. Cefiderocol total clearance (CLtot) was determined at each TDM assessment. fCss/MIC ratio was selected as PD determinant of cefiderocol efficacy and defined as optimal if >4, quasi-optimal if between 1 and 4, and suboptimal if <1. Results: Five patients with documented CRAB infections (two BSI+VAP, two VAP, and one BSI+cIAI) were included. The maintenance dose of cefiderocol was always of 2g q8h over 8h by CI. Median average fCss was 26.5 mg/L (21.7-33.6 mg/L). Median CLtot was 4.84 L/h (2.04-5.22 L/h). Median CVVHDF dose was 41.1 mL/kg/h (35.5-44.9 mL/kg/h), and residual diuresis was reported in 4/5 cases. Optimal PK/PD target was attained in all cases with a median cefiderocol fCss/MIC ratio of 14.9 (6.6-33.6). Conclusion: CI administration of full doses could be a useful strategy for attaining aggressive PK/PD targets with cefiderocol for the treatment of severe CRAB infections among critically ill patients undergoing high-intensity CVVHDF and having residual diuresis.