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Bacteriology

Cefiderocol Antimicrobial Susceptibility Testing against Multidrug-Resistant Gram-Negative Bacilli: a Comparison of Disk Diffusion to Broth Microdilution

C. Paul Morris, Yehudit Bergman, Tsigedera Tekle, John A. Fissel, Pranita D. Tamma, Patricia J. Simner
Carey-Ann D. Burnham, Editor
C. Paul Morris
aDivision of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
bNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA
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Yehudit Bergman
aDivision of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Tsigedera Tekle
aDivision of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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John A. Fissel
aDivision of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Pranita D. Tamma
cDivision of Pediatric Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Patricia J. Simner
aDivision of Medical Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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  • ORCID record for Patricia J. Simner
Carey-Ann D. Burnham
Washington University School of Medicine
Roles: Editor
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DOI: 10.1128/JCM.01649-20
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ABSTRACT

Antimicrobial susceptibility testing (AST) of cefiderocol poses challenges because of its unique mechanism of action (i.e., requiring an iron-depleted state) and due to differences in interpretative criteria established by the Clinical and Laboratory Standards Institute (CLSI), U.S. Food and Drug Administration (FDA), and European Committee on Antimicrobial Susceptibility Testing (EUCAST). Our objective was to compare cefiderocol disk diffusion methods (DD) to broth microdilution (BMD) for AST of Gram-negative bacilli (GNB). Cefiderocol AST was performed on consecutive carbapenem-resistant Enterobacterales (CRE; 58 isolates) and non-glucose-fermenting GNB (50 isolates) by BMD (lyophilized panels; Sensititre; Thermo Fisher) and DD (30 μg; research-use-only [RUO] MASTDISCS and FDA-cleared HardyDisks). Results were interpreted using FDA (prior to 28 September 2020 update), EUCAST, and investigational CLSI breakpoints (BPs). Categorical agreement (CA), minor errors (mE), major errors (ME), and very major errors (VME) were calculated for DD methods. The susceptibilities of all isolates by BMD were 72% (FDA), 75% (EUCAST) and 90% (CLSI). For DD methods, EUCAST BPs demonstrated lower susceptibility at 65% and 66%, compared to 74% and 72% (FDA) and 87% and 89% (CLSI) by HardyDisks and MASTDISCS, respectively. CA ranged from 75% to 90%, with 8 to 25% mE, 0 to 19% ME, and 0 to 20% VME and varied based on disk, GNB, and BPs evaluated. Both DD methods performed poorly for Acinetobacter baumannii complex. There is considerable variability when cefiderocol ASTs are interpreted using CLSI, FDA, and EUCAST breakpoints. DD offers a convenient alternative approach to BMD methods for cefiderocol AST, with the exception of A. baumannii complex isolates.

FOOTNOTES

    • Received 26 June 2020.
    • Returned for modification 20 August 2020.
    • Accepted 7 September 2020.
    • Accepted manuscript posted online 16 September 2020.
  • For companion articles on this topic, see https://doi.org/10.1128/JCM.00966-20 and https://doi.org/10.1128/JCM.00951-20.

  • Copyright © 2020 American Society for Microbiology.

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Cefiderocol Antimicrobial Susceptibility Testing against Multidrug-Resistant Gram-Negative Bacilli: a Comparison of Disk Diffusion to Broth Microdilution
C. Paul Morris, Yehudit Bergman, Tsigedera Tekle, John A. Fissel, Pranita D. Tamma, Patricia J. Simner
Journal of Clinical Microbiology Dec 2020, 59 (1) e01649-20; DOI: 10.1128/JCM.01649-20

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Cefiderocol Antimicrobial Susceptibility Testing against Multidrug-Resistant Gram-Negative Bacilli: a Comparison of Disk Diffusion to Broth Microdilution
C. Paul Morris, Yehudit Bergman, Tsigedera Tekle, John A. Fissel, Pranita D. Tamma, Patricia J. Simner
Journal of Clinical Microbiology Dec 2020, 59 (1) e01649-20; DOI: 10.1128/JCM.01649-20
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KEYWORDS

cefiderocol
antimicrobial susceptibility testing
broth microdilution
disk diffusion

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