Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jan 25;62(2):e01968-17.
doi: 10.1128/AAC.01968-17. Print 2018 Feb.

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

Meredith A Hackel  1 , Masakatsu Tsuji  2 , Yoshinori Yamano  3 , Roger Echols  4 , James A Karlowsky  5 , Daniel F Sahm  6
Affiliations

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

Meredith A Hackel et al. Antimicrob Agents Chemother. .

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.

Keywords: Gram-negative bacilli; carbapenem-nonsusceptible; cefiderocol; multidrug-resistant; siderophore.

PubMed Disclaimer

Figures

FIG 1
FIG 1
Cumulative cefiderocol MIC distribution (percentage of isolates) for 1,022 isolates of meropenem-nonsusceptible Enterobacteriaceae.
FIG 2
FIG 2
Cefiderocol MIC distributions for all isolates of carbapenem-nonsusceptible Enterobacteriaceae (white bars; n = 1,022), isolates of carbapenem-nonsusceptible Enterobacteriaceae that were concurrently nonsusceptible to ceftolozane-tazobactam (gray bars; n = 1,005), and isolates of carbapenem-nonsusceptible Enterobacteriaceae that were concurrently nonsusceptible to ceftazidime-avibactam (black bars; n = 235).
FIG 3
FIG 3
Cumulative cefiderocol MIC distribution (percentage of isolates) for 368 isolates of MDR A. baumannii.
FIG 4
FIG 4
Cefiderocol MIC distributions for all isolates of MDR P. aeruginosa (white bars; n = 262), isolates of MDR P. aeruginosa that were concurrently nonsusceptible to ceftolozane-tazobactam (gray bars; n = 199), and isolates of MDR P. aeruginosa that were concurrently nonsusceptible to ceftazidime-avibactam (black bars; n = 167).
FIG 5
FIG 5
Cumulative cefiderocol MIC distribution (percentage of isolates) for 262 isolates of MDR P. aeruginosa.
FIG 6
FIG 6
Cumulative cefiderocol MIC distribution (percentage of isolates) for 217 isolates of S. maltophilia.
See this image and copyright information in PMC

References

    1. Kazmierczak KM, Biedenbach DJ, Hackel M, Rabine S, de Jonge BLM, Bouchillon SK, Sahm DF, Bradford PA. 2016. Global dissemination of blaKPC into bacterial species beyond Klebsiella pneumoniae and in vitro susceptibility to ceftazidime-avibactam and aztreonam-avibactam. Antimicrob Agents Chemother 60:4490–4500. doi:10.1128/AAC.00107-16. - DOI - PMC - PubMed
    1. de Jonge BLM, Karlowsky JA, Kazmierczak KM, Biedenbach DJ, Sahm DF, Nichols WW. 2016. In vitro susceptibility to ceftazidime-avibactam of carbapenem-nonsusceptible Enterobacteriaceae isolates collected during the INFORM global surveillance study (2012 to 2014). Antimicrob Agents Chemother 60:3163–3169. doi:10.1128/AAC.03042-15. - DOI - PMC - PubMed
    1. Zilberberg MD, Kollef MH, Shorr AF. 2016. Secular trends in Acinetobacter baumannii resistance in respiratory and blood stream specimens in the United States, 2003 to 2012: a survey study. J Hosp Med 11:21–26. doi:10.1002/jhm.2477. - DOI - PubMed
    1. Labarca JA, Costa Sallas MJ, Seas C, Guzmàn-Blanco M. 2014. Carbapenem resistance in Pseudomonas aeruginosa and Acinetobacter baumannii in the nosocomial setting in Latin America. Crit Rev Microbiol 42:276–292. doi:10.3109/1040841X.2014.940494. - DOI - PubMed
    1. Clinical and Laboratory Standards Institute. 2017. Performance standards for antimicrobial susceptibility testing; twenty-seventh informational supplement. CLSI document M100-S27. CLSI, Wayne, PA.

Publication types

MeSH terms