In Vitro 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 in vitro 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 Enterobacteriaceae (n = 1,022), multidrug-resistant (MDR) Acinetobacter baumannii (n = 368), MDR Pseudomonas aeruginosa (n = 262), Stenotrophomonas maltophilia (n = 217), and Burkholderia cepacia (n = 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 Enterobacteriaceae 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 A. baumannii, MDR P. aeruginosa, and S. maltophilia 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 B. cepacia ranged from 0.004 to 8 μg/ml. We conclude that cefiderocol demonstrated potent in vitro activity against a 2014–2016, worldwide collection of clinical isolates of carbapenem-nonsusceptible Enterobacteriaceae, MDR A. baumannii, MDR P. aeruginosa, S. maltophilia, and B. cepacia isolates as 96.2% of all (1,801/1,873) isolates tested had cefiderocol MICs of ≤4 μg/ml.

ARGONAUT-I: Activity of Cefiderocol (S-649266), a Siderophore Cephalosporin, against Gram-Negative Bacteria, Including Carbapenem-Resistant Nonfermenters and Enterobacteriaceae with Defined Extended-Spectrum β-Lactamases and Carbapenemases

“…For A. baumannii our MIC 90 of 1 mg/liter was in agreement with the MIC 90 values of 1 and 2 mg/liter, respectively, reported by Ito et al (10) and Hackel et al (29), while a later publication by Hackel et al reported a higher MIC 90 value of 8 mg/liter (30). The reason for this difference in activity against A. baumannii may be associated with regional differences in the resistance mechanisms of this species.…”

New Treatment Options against Carbapenem-Resistant Acinetobacter baumannii Infections

“…In in vitro studies, cefiderocol was shown to be potent against OXA-23, OXA-40, and OXA-58 as well as NDM-and IMP-producing A. baumannii isolates, with MIC 90 s ranging from 1 to 8 g/ml (35)(36)(37)(38)(39)(40). However, it seems to be less active against some strains of A. baumannii that express OXA-23 and OXA-40 (38,40,41).…”

Antimicrobial Activity of Gallium Compounds on ESKAPE Pathogens

“…In this study, the antibacterial activity of three compounds belonging to the first-, second-, and third-generation Ga(III) formulations, i.e., GaN, GaM, and GaPPIX, was tested on ESKAPE pathogens in culture media characterized by different iron content, namely Mueller-Hinton broth (MHB), iron-deprived MHB (DMHB) (Hackel et al, 2018 ) and RPMI-1640 tissue culture medium supplemented with 10% complement-free human serum (RPMI-HS), to better mimic the in vivo environment (Antunes et al, 2012 ; Thompson et al, 2012 ; Bonchi et al, 2015 ). ESKAPE bacteria resulted more susceptible to Ga(III) compounds in RPMI-HS than in MHB and DMHB.…”