International journal of antimicrobial agents · 2025
Cefiderocol pharmacokinetics in critically-ill patients receiving extra-corporeal membrane oxygenation (ECMO).
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Koenig Christina, Fratoni Andrew J, Abouelhassan Yasmeen, Gluck Jason A, Nicolau David P, Kuti Joseph L
Аннотация
OBJECTIVE: Critical illness and organ support such as extracorporeal membrane oxygenation (ECMO) may influence antimicrobial pharmacokinetics. This study investigated cefiderocol pharmacokinetics in critically-ill patients receiving ECMO to understand if standard dosing achieves optimal exposure.
METHODS: Cefiderocol was prescribed according to approved package insert recommendations based on creatinine clearance (CL). Blood sampling was performed at steady-state. Protein binding was determined by ultrafiltration. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. The fT > MIC for each patient was assessed at MICs of 4, 8, and 16 mg/L. Total AUC24h was calculated to evaluate comparative exposure to non-ECMO patients.
RESULTS: Five patients receiving 1.5 g q8h to 2 g q6h dosing regimens were enrolled. Three patients received venous-arterial and two veno-venous ECMO (mean flow rate of 3.9 [range: 2.7-4.9] L/min). A two-compartment model fitted the data best with mean ± standard deviation estimates for CL, volume of the central compartment (V), K12, and K21 of 2.3 ± 0.5 L/h, 4.8 ± 2.3 L, 5.1 ± 2.8 h-1, and 3.9 ± 3.3 h-1, respectively. Mean protein binding was 41% (range: 31%-50%). Prescribed dosing regimens achieved 100% fT > MIC up to 16 mg/L for all patients, with a total steady-state AUC24h of 2501 (range: 1631-3276) mg/L·h.
CONCLUSIONS: These are the first data to describe cefiderocol pharmacokinetics in critically-ill patients undergoing ECMO. The currently labelled dosing recommendations based on creatinine CL in these patients were well tolerated and achieved 100% fT > MIC against susceptible bacteria and AUC exposures similar to values in non-ECMO patients.
METHODS: Cefiderocol was prescribed according to approved package insert recommendations based on creatinine clearance (CL). Blood sampling was performed at steady-state. Protein binding was determined by ultrafiltration. Concentrations were fitted using the non-parametric adaptive grid algorithm in Pmetrics for R. The fT > MIC for each patient was assessed at MICs of 4, 8, and 16 mg/L. Total AUC24h was calculated to evaluate comparative exposure to non-ECMO patients.
RESULTS: Five patients receiving 1.5 g q8h to 2 g q6h dosing regimens were enrolled. Three patients received venous-arterial and two veno-venous ECMO (mean flow rate of 3.9 [range: 2.7-4.9] L/min). A two-compartment model fitted the data best with mean ± standard deviation estimates for CL, volume of the central compartment (V), K12, and K21 of 2.3 ± 0.5 L/h, 4.8 ± 2.3 L, 5.1 ± 2.8 h-1, and 3.9 ± 3.3 h-1, respectively. Mean protein binding was 41% (range: 31%-50%). Prescribed dosing regimens achieved 100% fT > MIC up to 16 mg/L for all patients, with a total steady-state AUC24h of 2501 (range: 1631-3276) mg/L·h.
CONCLUSIONS: These are the first data to describe cefiderocol pharmacokinetics in critically-ill patients undergoing ECMO. The currently labelled dosing recommendations based on creatinine CL in these patients were well tolerated and achieved 100% fT > MIC against susceptible bacteria and AUC exposures similar to values in non-ECMO patients.