Abstract
Herein, we evaluated sustainability of humanized exposures of cefiderocol in vivo over 72 h against pathogens with cefiderocol MICs of 0.5 to 16 μg/ml in the neutropenic murine thigh model. In Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae displaying MICs of 0.5 to 8 μg/ml (n = 11), sustained kill was observed at 72 h among 9 isolates. Postexposure MICs revealed a single 2-dilution increase in one animal compared with controls (1/54 samples, 1.8%) at 72 h. Adaptive resistance during therapy was not observed.
Highlights
We evaluated sustainability of humanized exposures of cefiderocol in vivo over 72 h against pathogens with cefiderocol MICs of 0.5 to 16 g/ml in the neutropenic murine thigh model
The effect of humanized doses of cefiderocol, a novel siderophore cephalosporin, was recently characterized across a wide array of clinical isolates in the neutropenic murine thigh infection model. Data from these 24-h pharmacodynamic studies revealed that cefiderocol humanized exposures produced predictable bacterial kill against multidrug resistant (MDR) Gram-negative isolates with MICs (MICs) of Յ4 g/ml [3]
A total of 12 Gram-negative isolates (2 Pseudomonas aeruginosa isolates, 4 Acinetobacter baumannii isolates, and 6 Enterobacteriaceae isolates) with cefiderocol MICs ranging from 0.5 to 16 g/ml were provided by Shionogi & Co., Ltd., or International Health Management Associates (IHMA), Inc
Summary
We evaluated sustainability of humanized exposures of cefiderocol in vivo over 72 h against pathogens with cefiderocol MICs of 0.5 to 16 g/ml in the neutropenic murine thigh model. Data from these 24-h pharmacodynamic studies revealed that cefiderocol humanized exposures produced predictable bacterial kill against multidrug resistant (MDR) Gram-negative isolates with MICs (MICs) of Յ4 g/ml [3]. The cefiderocol dosing regimen utilized has been validated in several studies with the same mouse model to provide exposures equivalent to those in humans attained after administration of 2 g every 8 h (q8h) (3 h infusion) [3, 6, 7].
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