Clinical Pharmacokinetics and Pharmacodynamics of Cefiderocol - Kölner UniversitätsPublikationsServer

Bilal, Muhammad, El Tabei, Lobna, Buesker, Soeren, Krauss, Christian, Fuhr, Uwe and Taubert, Max (2021). Clinical Pharmacokinetics and Pharmacodynamics of Cefiderocol. Clin. Pharmacokinet., 60 (12). S. 1495 - 1509. NORTHCOTE: ADIS INT LTD. ISSN 1179-1926

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DOI:10.1007/s40262-021-01063-5

Abstract

Cefiderocol is a new broad-spectrum cephalosporin antibiotic with promising activity against various Gram-negative bacteria including carbapenem-resistant strains. A chlorocatechol group in the C-3 side chain provides cefiderocol with a siderophore activity, improving its stability against beta-lactamases and facilitating the transportation of cefiderocol across outer bacterial membranes. Cefiderocol shows linear pharmacokinetics over a broad range of clinically relevant doses, with unchanged renal excretion constituting the main route of elimination. Geometric means (coefficient of variation) of the volume of distribution and clearance in individuals with normal kidney function were 15.8 (15%) L and 4.70 (27%) L/h, respectively. In patients with end-stage renal disease, clearance was 1.10 (24%) L/h. Time above the minimum inhibitory concentration is the main predictor of efficacy. There is no evidence for clinically relevant interactions of cefiderocol with other drugs mediated by metabolizing enzymes or drug transporters. Simulations based on population pharmacokinetic modeling suggest that dosing regimens should be adjusted based on kidney function to optimize therapeutic exposure to cefiderocol. Clinical efficacy trials indicated that cefiderocol is non-inferior to imipenem/cilastatin in the treatment of complicated urinary tract infections and acute uncomplicated pyelonephritis, and to meropenem in the treatment of nosocomial pneumonia. In the one study currently available, cefiderocol performed similarly to the best available therapy in the treatment of severe carbapenem-resistant Gram-negative infections regarding clinical and microbiological efficacy. In summary, cefiderocol shows favorable pharmacokinetic/pharmacodynamic properties and an acceptable safety profile, suggesting that cefiderocol might be a viable option to treat infections with bacteria resistant to other antibiotics.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Bilal, Muhammad	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
El Tabei, Lobna	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Buesker, Soeren	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Krauss, Christian	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Fuhr, Uwe	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Taubert, Max	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED