<i>In Vitro</i> Activity of the Siderophore Cephalosporin, Cefiderocol, against Carbapenem-Nonsusceptible and Multidrug-Resistant Isolates of Gram-Negative Bacilli Collected Worldwide in 2014 to 2016

Abstract

The <i>in vitro</i> 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-nonsusceptible <i>Enterobacteriaceae</i> (<i>n</i> = 1,022), multidrug-resistant (MDR) <i>Acinetobacter baumannii</i> (<i>n</i> = 368), MDR <i>Pseudomonas aeruginosa</i> (<i>n</i> = 262), <i>Stenotrophomonas maltophilia</i> (<i>n</i> = 217), and <i>Burkholderia cepacia</i> (<i>n</i> = 4) using the Clinical and Laboratory Standards Institute (CLSI) standard broth microdilution method. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB), prepared according to a 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% (MIC₉₀) of isolates of carbapenem-nonsusceptible <i>Enterobacteriaceae</i> 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 of ≤4 μg/ml. The MIC₉₀s for cefiderocol for MDR <i>A. baumannii</i>, MDR <i>P. aeruginosa</i>, and <i>S. maltophilia</i> 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 of ≤4 μg/ml. Cefiderocol MICs for <i>B. cepacia</i> ranged from 0.004 to 8 μg/ml. We conclude that cefiderocol demonstrated potent <i>in vitro</i> activity against a 2014-2016, worldwide collection of clinical isolates of carbapenem-nonsusceptible <i>Enterobacteriaceae</i>, MDR <i>A. baumannii</i>, MDR <i>P. aeruginosa</i>, <i>S. maltophilia</i>, and <i>B. cepacia</i> isolates as 96.2% of all (1,801/1,873) isolates tested had cefiderocol MICs of ≤4 μg/ml.