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  • Title: 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).
    Author: Gatti M, Rinaldi M, Tonetti T, Gaibani P, Siniscalchi A, Viale P, Pea F.
    Journal: Int J Antimicrob Agents; 2023 Aug; 62(2):106852. PubMed ID: 37192727.
    Abstract:
    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 cefiderocol by CI 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 a PD determinant of cefiderocol efficacy and defined as optimal (>4), quasi-optimal (1-4), and suboptimal (<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 2 g q8h over 8 h 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 of full doses of cefiderocol could be a useful strategy to attain aggressive PK/PD targets for the treatment of severe CRAB infections in critically ill patients undergoing high-intensity CVVHDF and who have residual diuresis.
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