In Vitro Activity of the Siderophore Cephalosporin, Cefiderocol, Against Carbapenem-Non-Susceptible and Multidrug-Resistant Isolates of Gram-Negative Bacilli Collected Worldwide in 2014-2016 [PublishAheadOfPrint]

The in vitro activity of the investigational siderophore cephalosporin, cefiderocol (formerly S-649266), was determined against a 2014-2016, 52-country, worldwide collection of clinical isolates of carbapenem-non-susceptible Enterobacteriaceae (n=1,022), multidrug-resistant (MDR) Acinetobacter baumannii (n=368), MDR Pseudomonas aeruginosa (n=262), Stenotrophomonas maltophilia (n=217), and Burkholderia cepacia (n=4) using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB), prepared following the recently approved (2017), but not yet published, CLSI protocol, was used to test cefiderocol; all other antimicrobial agents were tested using CAMHB. The concentration of cefiderocol inhibiting 90% of isolates of carbapenem-non-susceptible Enterobacteriaceae (MIC₉₀) was 4 μg/ml; cefiderocol MICs ranged from 0.004 to 32 μg/ml and 97.0% (991/1,022) of isolates demonstrated cefiderocol MICs ≤4 μg/ml. The MIC₉₀s for cefiderocol for MDR A. baumannii, MDR P. aeruginosa, and S. maltophilia were 8, 1, and 0.25 μg/ml, respectively, with 89.7% (330/368), 99.2% (260/262), and 100% (217/217) of isolates demonstrating cefiderocol MICs ≤4 μg/ml. Cefiderocol MICs for B. cepacia ranged from 0.004-8 μg/ml. We conclude that cefiderocol demonstrated potent in vitro activity against a 2014-2016, worldwide collection of clinical isolates of carbapenem non-susceptible Enterobacteriaceae, MDR A. baumannii, MDR P. aeruginosa, S. maltophilia, and B. cepacia as 96.2% of all (1,801/1,873) isolates tested had cefiderocol MICs ≤4 μg/ml.

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