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)

Milo Gatti; Matteo Rinaldi; Tommaso Tonetti; Paolo Gaibani; Antonio Siniscalchi; Pierluigi Viale; Federico Pea

doi:10.1016/j.ijantimicag.2023.106852

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)

Int J Antimicrob Agents. 2023 Aug;62(2):106852. doi: 10.1016/j.ijantimicag.2023.106852. Epub 2023 May 14.

Authors

Milo Gatti¹, Matteo Rinaldi², Tommaso Tonetti³, Paolo Gaibani⁴, Antonio Siniscalchi⁵, Pierluigi Viale², Federico Pea⁶

Affiliations

¹ Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy. Electronic address: milo.gatti2@unibo.it.
² Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Infectious Diseases Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
³ Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Division of Anesthesiology, Department of Anesthesia and Intensive Care, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁴ Operative Unit of Microbiology, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁵ Anesthesia and Intensive Care Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
⁶ Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, Bologna, Italy; Clinical Pharmacology Unit, Department for Integrated Infectious Risk Management, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.

PMID: 37192727
DOI: 10.1016/j.ijantimicag.2023.106852

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 (fC_ss) was calculated. Cefiderocol total clearance (CL_tot) was determined at each TDM assessment. fC_ss/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 fC_ss was 26.5 mg/L (21.7-33.6 mg/L). Median CL_tot 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 fC_ss/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.

Keywords: Carbapenem-resistant Acinetobacter baumannii; Cefiderocol; Continuous infusion; Continuous renal replacement therapy; Continuous venovenous haemodiafiltration; PK/PD target attainment.

MeSH terms

Acinetobacter baumannii*
Anti-Bacterial Agents / therapeutic use
Carbapenems / pharmacology
Carbapenems / therapeutic use
Cefiderocol
Continuous Renal Replacement Therapy*
Critical Illness
Hemodiafiltration*
Humans
Retrospective Studies

Substances

Anti-Bacterial Agents
Carbapenems