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

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