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Cefiderocol is Not Sequestered in an Ex Vivo Extracorporeal Membrane Oxygenation (ECMO) Circuit

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Abstract

Background and Objective

Extracorporeal membrane oxygenation (ECMO) is used in critically ill patients that require respiratory and/or cardiac support. Cefiderocol is a novel siderophore antibiotic that may require use in infected critically ill patients supported by ECMO. The objective of this study was to determine the loss of cefiderocol through an ex vivo adult ECMO circuit using a Quadrox-iD oxygenator.

Methods

A 3/8-inch, simulated, ex vivo closed-loop ECMO circuit was prepared with a Quadrox-iD adult oxygenator and primed with fresh whole blood. Cefiderocol was administered into the circuit to achieve a starting concentration of approximately 90 mg/L. Post-oxygenator blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 12, and 24 h after the addition of the drug to determine the loss in the circuit. A glass control jar was prepared with the same blood matrix and maintained at the same temperature to determine drug degradation. The experiment was conducted in triplicate. The rate of cefiderocol loss in the ECMO circuit was compared with that in the control by one-way analysis of variance.

Results

At 0 h, the difference between the pre- and post-oxygenator concentrations was − 4 ± 4% (range 0 to − 7%). After 24 h, the cefiderocol percent reduction was similar between the ECMO circuit and control (50% ± 13 vs. 50% ± 9, p = 1.0).

Conclusions

The degradation rate of cefiderocol did not differ significantly within the ECMO circuit and control, suggesting no loss due to sequestration or adsorption. Pharmacokinetic studies in patients supported by ECMO are warranted to determine final dosing recommendations.

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Acknowledgements

We acknowledge Tyler Ackley, Jennifer Tabor-Rennie, Alissa Padgett, and Elizabeth Cyr for assistance with the conduct of these ex vivo experiments.

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Authors and Affiliations

  1. Center for Anti-Infective Research and Development, Hartford Hospital, 80 Seymour Street, Hartford, CT, 06102, USA

    Angela V. Berry, David P. Nicolau & Joseph L. Kuti

  2. Heart and Vascular Institute, Hartford Hospital, Hartford, CT, USA

    Allison Conelius & Jason A. Gluck

Authors
  1. Angela V. Berry
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  2. Allison Conelius
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  3. Jason A. Gluck
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  4. David P. Nicolau
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  5. Joseph L. Kuti
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Corresponding author

Correspondence to Joseph L. Kuti.

Ethics declarations

Ethics Approval and Consent to Participate

The study was reviewed and approved by the Hartford Healthcare Institutional Review Board. Healthy volunteer participants provided written informed consent to donate blood for the study.

Consent for Publication

Not applicable.

Availability of Data and Materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Code Availability

Not applicable.

Conflict of Interests

JLK and DPN are members of the Shionogi Speakers’ Bureau and have participated in advisory boards. The remaining authors have nothing to disclose.

Funding

This study was supported by an investigator-initiated trial grant from Shionogi Inc. (Florham Park, NJ). Shionigi Inc. had no role in the study design, conduct, interpretation of data, or writing of the manuscript.

Authors’ Contributions

Study concept and methodology design: JLK, DPN, AC, JAG; protocol writing: JLK; study conduct: AVB, AC, JLK; data analyses: AVB, JLK; data interpretation: AVB, JAG, DPN, JLK; manuscript writing: AVB, JLK; manuscript review: AVB, AC, JAG, DPN, JLK.

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Berry, A.V., Conelius, A., Gluck, J.A. et al. Cefiderocol is Not Sequestered in an Ex Vivo Extracorporeal Membrane Oxygenation (ECMO) Circuit. Eur J Drug Metab Pharmacokinet 48, 437–441 (2023). https://doi.org/10.1007/s13318-023-00840-w

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  • DOI: https://doi.org/10.1007/s13318-023-00840-w

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