In Vitro 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 (n = 4,239) and Europe (n = 4,966). The concentrations of cefiderocol inhibiting 90% of isolates tested (MIC₉₀s) were 0.5 μg/ml (North America; n = 3,007) and 1 μg/ml (Europe; n = 3,080) for all isolates of Enterobacteriaceae; 1 μg/ml (North America; n = 30) and 4 μg/ml (Europe; n = 139) for meropenem-nonsusceptible (MIC ≥ 2 μg/ml) isolates of Enterobacteriaceae; 0.5 μg/ml for both North American (n = 765) and European (n = 765) isolates of Pseudomonas aeruginosa; 0.5 μg/ml (North America; n = 151) and 1 μg/ml (Europe; n = 202) for meropenem-nonsusceptible (MIC ≥ 4 μg/ml) isolates of P. aeruginosa; 1 μg/ml for both North American (n = 309) and European (n = 839) isolates of all Acinetobacter baumannii strains as well as for both North American (n = 173) and European (n = 595) isolates of meropenem-nonsusceptible A. baumannii; and 0.5μg/ml (North America; n = 152) and 0.25 μg/ml (Europe; n = 276) for isolates of Stenotrophomonas maltophilia MICs of cefiderocol were ≤4 μg/ml for 99.9% (6,078/6,087) of all Enterobacteriaceae, 97.0% (164/169) of meropenem-nonsusceptible Enterobacteriaceae, 99.9% (1,529/1,530) of all P. aeruginosa isolates, 100% (353/353) of meropenem-nonsusceptible P. aeruginosa isolates, 97.6% (1,120/1,148) of all A. baumannii isolates, 96.9% (744/768) of meropenem-nonsusceptible A. baumannii isolates, 100% of isolates of S. maltophilia (428/428) and 93.8% of isolates of Burkholderia cepecia (11/12). We conclude that cefiderocol demonstrated potent in vitro activity against a recent collection of clinical isolates of commonly encountered Gram-negative bacilli, including carbapenem-nonsusceptible isolates.

Keywords: Chelex 100 resin; Gram-negative bacteria; carbapenem-resistant; cefiderocol; siderophore.

FIG 1

Cefiderocol MIC distributions for meropenem-nonsusceptible Enterobacteriaceae (white bars; n = 30), P. aeruginosa (gray bars; n = 151), and A. baumannii (black bars; n = 173) isolates collected by North American medical center laboratories.

FIG 2

Cefiderocol MIC distributions for meropenem-nonsusceptible Enterobacteriaceae (white bars; n = 139), P. aeruginosa (gray bars; n = 202), and A. baumannii (black bars; n = 595) isolates collected by European medical center laboratories.

FIG 3

Cumulative MIC susceptibility curves for cefiderocol and comparators against 169 meropenem nonsusceptible Enterobacteriaceae from North American and European medical center laboratories. For colistin and ciprofloxacin, the endpoint of their respective cumulative MIC susceptibility curves represents the highest concentration tested. The remaining tested isolates had MICs higher than their endpoint value.

FIG 4

Cumulative MIC susceptibility curves for cefiderocol and comparators against 353 meropenem-nonsusceptible P. aeruginosa isolates from North American and European medical center laboratories. For colistin and ciprofloxacin, the endpoint of their respective cumulative MIC susceptibility curves represents the highest concentration tested. The remaining tested isolates had MICs higher than their endpoint value.

FIG 5

Cumulative MIC susceptibility curves for cefiderocol and comparators against 768 meropenem-nonsusceptible A. baumannii isolates from European and North American medical center laboratories. For colistin and ciprofloxacin, the endpoint of their respective cumulative MIC susceptibility curves represents the highest concentration tested. The remaining tested isolates had MICs higher than their endpoint value.