Skip to main content
Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics 4/2023

23.06.2023 | Original Research Article

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

verfasst von: Angela V. Berry, Allison Conelius, Jason A. Gluck, David P. Nicolau, Joseph L. Kuti

Erschienen in: European Journal of Drug Metabolism and Pharmacokinetics | Ausgabe 4/2023

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat Bartlett RH, Gattinoni L. Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76:534–40.PubMed Bartlett RH, Gattinoni L. Current status of extracorporeal life support (ECMO) for cardiopulmonary failure. Minerva Anestesiol. 2010;76:534–40.PubMed
2.
Zurück zum Zitat Sherwin J, Heath T, Watt K. Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: a review of the current literature. Clin Ther. 2016;38:1976–94.CrossRefPubMedPubMedCentral Sherwin J, Heath T, Watt K. Pharmacokinetics and dosing of anti-infective drugs in patients on extracorporeal membrane oxygenation: a review of the current literature. Clin Ther. 2016;38:1976–94.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Shekar K, Roberts JA, McDonald CI, Fisquet S, Barnett AG, Mullany DV, et al. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012;16:R194.CrossRefPubMedPubMedCentral Shekar K, Roberts JA, McDonald CI, Fisquet S, Barnett AG, Mullany DV, et al. Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation. Crit Care. 2012;16:R194.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Wu JY, Srinivas P, Pogue JM. Cefiderocol: a novel agent for the management of multidrug-resistant gram-negative organisms. Infect Dis Ther. 2020;9:17–40.CrossRefPubMedPubMedCentral Wu JY, Srinivas P, Pogue JM. Cefiderocol: a novel agent for the management of multidrug-resistant gram-negative organisms. Infect Dis Ther. 2020;9:17–40.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Cies JJ, Nikolos P, Moore WS 2nd, Giliam N, Low T, Marino D, et al. Oxygenator impact on meropenem/vaborbactam in extracorporeal membrane oxygenation circuits. Perfusion. 2022;37:729–37.CrossRefPubMed Cies JJ, Nikolos P, Moore WS 2nd, Giliam N, Low T, Marino D, et al. Oxygenator impact on meropenem/vaborbactam in extracorporeal membrane oxygenation circuits. Perfusion. 2022;37:729–37.CrossRefPubMed
6.
Zurück zum Zitat Shionogi Inc. Cefiderocol (Fetroja) package insert. Florham Park: Shionogi Inc.; 2020. Shionogi Inc. Cefiderocol (Fetroja) package insert. Florham Park: Shionogi Inc.; 2020.
7.
Zurück zum Zitat Shekar K, Roberts JA, McDonald CI, Ghassabian S, Anstey C, Wallis SC, et al. Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study. Crit Care. 2015;19:164.CrossRefPubMedPubMedCentral Shekar K, Roberts JA, McDonald CI, Ghassabian S, Anstey C, Wallis SC, et al. Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study. Crit Care. 2015;19:164.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Shekar K, Roberts JA, Barnett AG, Diab S, Wallis SC, Fung YL, et al. Can physiochemical properties of antimicrobials be used to predict their pharmacokinetics during extracoproreal membrane oxygenation? Illustrative data from ovine models. Crit Care. 2015;19:437.CrossRefPubMedPubMedCentral Shekar K, Roberts JA, Barnett AG, Diab S, Wallis SC, Fung YL, et al. Can physiochemical properties of antimicrobials be used to predict their pharmacokinetics during extracoproreal membrane oxygenation? Illustrative data from ovine models. Crit Care. 2015;19:437.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46:D1074–82.CrossRefPubMed Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46:D1074–82.CrossRefPubMed
10.
Zurück zum Zitat Tron C, Leven C, Fillatre P, Maillard N, Nesseler N, Tattevin P, et al. Should we fear tubing adsorption of antibacterial drugs in extracoproreal membrane oxygenation? An answer for cepahlosporins and carbapenems. Clin Exp Pharmacol Physiol. 2016;43:281–3.CrossRefPubMed Tron C, Leven C, Fillatre P, Maillard N, Nesseler N, Tattevin P, et al. Should we fear tubing adsorption of antibacterial drugs in extracoproreal membrane oxygenation? An answer for cepahlosporins and carbapenems. Clin Exp Pharmacol Physiol. 2016;43:281–3.CrossRefPubMed
11.
Zurück zum Zitat Leven C, Fillatre P, Petitcollin A, Verdier MC, Laurent J, Nesseler N, et al. Ex vivo model to decipher the impact of extracorporeal membrane oxygenation on beta-lactam degradation kinetics. Ther Drug Monit. 2017;39:180–4.CrossRefPubMed Leven C, Fillatre P, Petitcollin A, Verdier MC, Laurent J, Nesseler N, et al. Ex vivo model to decipher the impact of extracorporeal membrane oxygenation on beta-lactam degradation kinetics. Ther Drug Monit. 2017;39:180–4.CrossRefPubMed
13.
Zurück zum Zitat Mane C, Delmas C, Porerie J, Jourdan G, Verwaerde P, Marcheix B, et al. Influence of extracorporeal membrane oxygenation on the pharamcokinetics of ceftaroline/tazobactam: an ex vivo and in vivo study. J Transl Med. 2020;19:213.CrossRef Mane C, Delmas C, Porerie J, Jourdan G, Verwaerde P, Marcheix B, et al. Influence of extracorporeal membrane oxygenation on the pharamcokinetics of ceftaroline/tazobactam: an ex vivo and in vivo study. J Transl Med. 2020;19:213.CrossRef
14.
Zurück zum Zitat Lee JH, Lee DH, Kim JS, Jung WB, Heo W, Kim YK, et al. Pharmacokinetics and Monte Carlo simulation of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation. Front Pharmacol. 2021;12: 768912.CrossRefPubMedPubMedCentral Lee JH, Lee DH, Kim JS, Jung WB, Heo W, Kim YK, et al. Pharmacokinetics and Monte Carlo simulation of meropenem in critically ill adult patients receiving extracorporeal membrane oxygenation. Front Pharmacol. 2021;12: 768912.CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Gijsen M, Dreesen E, Annaert P, Nicolai J, Debaveye Y, Wauters J, et al. Meropenem pharmacokinetics and target attainment in critically ill patients are not affected by extracorporeal membrane exygenation: a matched cohort analysis. Microogranisms. 2021;9:1310.CrossRef Gijsen M, Dreesen E, Annaert P, Nicolai J, Debaveye Y, Wauters J, et al. Meropenem pharmacokinetics and target attainment in critically ill patients are not affected by extracorporeal membrane exygenation: a matched cohort analysis. Microogranisms. 2021;9:1310.CrossRef
Metadaten
Titel
Cefiderocol is Not Sequestered in an Ex Vivo Extracorporeal Membrane Oxygenation (ECMO) Circuit
verfasst von
Angela V. Berry
Allison Conelius
Jason A. Gluck
David P. Nicolau
Joseph L. Kuti
Publikationsdatum
23.06.2023
Verlag
Springer International Publishing
Erschienen in
European Journal of Drug Metabolism and Pharmacokinetics / Ausgabe 4/2023
Print ISSN: 0378-7966
Elektronische ISSN: 2107-0180
DOI
https://doi.org/10.1007/s13318-023-00840-w

Weitere Artikel der Ausgabe 4/2023

European Journal of Drug Metabolism and Pharmacokinetics 4/2023 Zur Ausgabe