Abstract
ABSTRACTCefiderocol (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.
Highlights
The in vitro activities of cefiderocol and comparators are summarized in Table 1 for the 4,239 isolates collected from North American medical center laboratories and in Table 2 for the 4,966 isolates from European medical center laboratories
One isolate of Serratia marcescens from North America had a MIC to cefiderocol of 8 g/ml, while six isolates of K. pneumoniae, one isolate of Enterobacter aerogenes, and one isolate of S. marcescens from Europe had a MIC to cefiderocol of 8 g/ml
There are very few antimicrobial agents available to clinicians to treat patients infected with carbapenem-resistant Gram-negative bacilli, and the few agents that are accessible to treat systemic infections are associated with aac.asm.org 10
Summary
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 ϭ 4,239) and Europe (n ϭ 4,966). 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. Cefiderocol, formerly known as S-649226, is a novel siderophore cephalosporin for injection discovered by and currently in clinical development with Shionogi & Co., Ltd., to treat infections caused by carbapenem-resistant Gram-negative bacteria. The current study, SIDERO-WT-2014, tested a 2014-2015 collection of 9,205 clinical isolates of Gram-negative bacilli from patients in North America and Europe against cefiderocol and comparators using CLSI broth microdilution methodology. This study generated the first in vitro surveillance testing data for cefiderocol using the recently approved CLSI broth microdilution MIC determination method (20)
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