Journal
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 61, Issue 9, Pages -Publisher
AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.00093-17
Keywords
cefiderocol; siderophore; carbapenem-resistant; Chelex 100 resin; Gram-negative bacteria
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Funding
- Shionogi & Co., Ltd., Osaka, Japan
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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 (MIC(90)s) were 0.5 mu g/ml (North America; n = 3,007) and 1 mu g/ml (Europe; n = 3,080) for all isolates of Enterobacteriaceae; 1 mu g/ml (North America; n = 30) and 4 mu g/ml (Europe; n = 139) for meropenem-nonsusceptible (MIC >= 2 mu g/ml) isolates of Enterobacteriaceae; 0.5 mu g/ml for both North American (n = 765) and European (n = 765) isolates of Pseudomonas aeruginosa; 0.5 mu g/ml (North America; n = 151) and 1 mu g/ml (Europe; n = 202) for meropenem-nonsusceptible (MIC >= 4 mu g/ml) isolates of P. aeruginosa; 1 mu g/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 0.5 mu g/ml (North America; n = 152) and 0.25 mu g/ml (Europe; n = 276) for isolates of Stenotrophomonas maltophilia. MICs of cefiderocol were >= 4 mu g/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.
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