<i>In Vitro</i> Activity of the Siderophore Cephalosporin, Cefiderocol, against a Recent Collection of Clinically Relevant Gram-Negative Bacilli from North America and Europe, Including Carbapenem-Nonsusceptible Isolates (SIDERO-WT-2014 Study)

Abstract

Cefiderocol (formerly S-649266) is an investigational siderophore cephalosporin. Iron-depleted cation-adjusted Mueller-Hinton broth (ID-CAMHB) was prepared according to the Clinical and Laboratory Standards Institute (CLSI) protocol and used to perform broth microdilution testing of cefiderocol against a 2014-2015 collection of clinical isolates of Gram-negative bacilli from North America (<i>n</i> = 4,239) and Europe (<i>n</i> = 4,966). The concentrations of cefiderocol inhibiting 90% of isolates tested (MIC₉₀s) were 0.5 μg/ml (North America; <i>n</i> = 3,007) and 1 μg/ml (Europe; <i>n</i> = 3,080) for all isolates of <i>Enterobacteriaceae</i>; 1 μg/ml (North America; <i>n</i> = 30) and 4 μg/ml (Europe; <i>n</i> = 139) for meropenem-nonsusceptible (MIC ≥ 2 μg/ml) isolates of <i>Enterobacteriaceae</i>; 0.5 μg/ml for both North American (<i>n</i> = 765) and European (<i>n</i> = 765) isolates of <i>Pseudomonas aeruginosa</i>; 0.5 μg/ml (North America; <i>n</i> = 151) and 1 μg/ml (Europe; <i>n</i> = 202) for meropenem-nonsusceptible (MIC ≥ 4 μg/ml) isolates of <i>P. aeruginosa</i>; 1 μg/ml for both North American (<i>n</i> = 309) and European (<i>n</i> = 839) isolates of all <i>Acinetobacter baumannii</i> strains as well as for both North American (<i>n</i> = 173) and European (<i>n</i> = 595) isolates of meropenem-nonsusceptible <i>A. baumannii</i>; and 0.5μg/ml (North America; <i>n</i> = 152) and 0.25 μg/ml (Europe; <i>n</i> = 276) for isolates of <i>Stenotrophomonas maltophilia</i> MICs of cefiderocol were ≤4 μg/ml for 99.9% (6,078/6,087) of all <i>Enterobacteriaceae</i>, 97.0% (164/169) of meropenem-nonsusceptible <i>Enterobacteriaceae</i>, 99.9% (1,529/1,530) of all <i>P. aeruginosa</i> isolates, 100% (353/353) of meropenem-nonsusceptible <i>P. aeruginosa</i> isolates, 97.6% (1,120/1,148) of all <i>A. baumannii</i> isolates, 96.9% (744/768) of meropenem-nonsusceptible <i>A. baumannii</i> isolates, 100% of isolates of <i>S. maltophilia</i> (428/428) and 93.8% of isolates of <i>Burkholderia cepecia</i> (11/12). We conclude that cefiderocol demonstrated potent <i>in vitro</i> activity against a recent collection of clinical isolates of commonly encountered Gram-negative bacilli, including carbapenem-nonsusceptible isolates.