600. Cefiderocol is Not Sequestered in an Ex vivo Extracorporeal Membrane Oxygenation (ECMO) Circuit. (15th December 2022)

• Record Type: Journal Article
• Authors: Berry, Angela V; Conelius, Allison M; Gluck, Jason A; Nicolau, David P; Kuti, Joseph L
• Is Part Of: Open forum infectious diseases. Volume 9:(2022)Supplement 2
• Publication Date: 2022-12-15
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofac492.652
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: Background: ECMO is widely used in critically-ill patients that require respiratory and/or cardiac support, but may affect drug exposure by altering pharmacokinetics within patients or sequestering drugs in the circuit. Cefiderocol, a siderophore antibiotic with activity against multi-drug resistant gram-negative bacteria, may be used to treat serious infections in critically-ill patients supported by ECMO. Limited data are available to guide dosing in this population. Herein, we determined the loss of cefiderocol through an ex vivo ECMO circuit. Methods: A closed-loop ECMO circuit prepared with a Quadrox-i adult oxygenator and primed with Isolyte S was used during all experiments. Fresh whole blood collected from healthy volunteers was pooled, injected to replace priming fluid, and circulated at 4.5 L/min at 37° C. Cefiderocol was administered into the circuit at 0h to obtain peak plasma concentrations of ∼89.7 mg/L. A pre-oxygenator blood sample was taken at 0h to confirm baseline concentration. Post-oxygenator blood samples were collected between 0-24h to determine loss of cefiderocol in the circuit. A control jar of the same pooled matrix spiked with cefiderocol was maintained at 37° C for comparison. Each ECMO/control experiment was performed in triplicate. A general linear model was constructed to compare the rate of loss between the ECMO circuit and controls. Results: Baseline cefiderocol concentrations in the ECMO circuit and control jar ranged from 51.7-91.8 mg/L and 67.7-100.5 mg/L, respectively. At 0h, the difference in pre- vs post-oxygenator concentration was -4 ± 4% (range: 0-7%). After 24h, cefiderocol % reduction was similar between the ECMO circuits and controls (50% ± 13 vs 50% ± 9, p=1.0). The degradation rate of cefiderocol followed a zero order process and did not differ significantly between the circuit and control (slope: -0.0186 ± 0.0052 vs -0.0201 ± 0.0039, p=0.786). Conclusion: Cefiderocol was not sequestered in an ex vivo ECMO circuit studied with an adult oxygenator, suggesting insignificant removal from the circuit can be expected. Pharmacokinetic studies in critically ill patients supported by ECMO are warranted to determine final dosing recommendations in this population. Disclosures: David P. Nicolau, PharmD, Shionogi: Grant/Research Support Joseph L. Kuti, PharmD, Abbvie: Honoraria|bioMeriuex: Advisor/Consultant|bioMeriuex: Grant/Research Support|Contrafect: Grant/Research Support|Entasis: Grant/Research Support|Merck and Co: Grant/Research Support|Roche Diagnostics: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Shionogi: Honoraria|Summit: Grant/Research Support.