Performance of four fosfomycin susceptibility testing methods against an international collection of clinical Pseudomonas aeruginosa isolates

Elizabeth C. Smith, Hunter V. Brigman, Jadyn C. Anderson, Christopher L. Emery, Tiffany E. Bias, Phillip J. Bergen, Cornelia B. Landersdorfer, Elizabeth B. Hirsch

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Fosfomycin has been shown to have a wide spectrum of activity against multidrug-resistant Gram-negative bacteria; however, breakpoints have been established only for Escherichia coli or Enterobacterales per the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST), respectively. A lack of additional organism breakpoints limits clinical use of this agent and has prompted extrapolation of these interpretive categories to other organisms like Pseudomonas aeruginosa without supporting evidence. Further complicating the utility of fosfomycin is the specified method for MIC determination, namely, agar dilution, which is not widely available and is both labor and time intensive. We therefore sought to determine the susceptibility of a large international collection of P. aeruginosa isolates (n = 198) to fosfomycin and to compare testing agreement rates across four methods: agar dilution, broth microdilution, disk diffusion, and Etest. Results were interpreted according to CLSI E. coli breakpoints, with 49.0 to 85.8% considered susceptible, dependent upon the testing method used. Epidemiological cutoff values were calculated and determined to be 256 μg/ml and 512 μg/ml for agar dilution and broth microdilution, respectively. Agreement rates were analyzed using both agar dilution and broth microdilution with a resulting high essential agreement rate of 91.3% between the two susceptibility testing methods. These results indicate that broth microdilution may be a reliable method for fosfomycin susceptibility testing against P. aeruginosa and stress the need for P. aeruginosa-specific breakpoints.

Original languageEnglish (US)
Article numbere0112120
JournalJournal of clinical microbiology
Volume58
Issue number10
DOIs
StatePublished - Oct 2020

Bibliographical note

Funding Information:
E.B.H. has received an advisory board honorarium from Nabriva Therapeutics and grant funding from Merck. T.E.B. is a former employee of Nabriva Therapeutics and a current employee of bioMérieux. All others have no conflicts to disclose.

Funding Information:
We thank the University of Minnesota College of Pharmacy Melendy/Peters’ research scholarship for providing partial funding (to E.C.S.) for this study. We thank Anton Y. Peleg, Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia, and David Paterson, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia, for the provision of isolates.

Funding Information:
We thank the University of Minnesota College of Pharmacy Melendy/Peters' research scholarship for providing partial funding (to E.C.S.) for this study. We thank Anton Y. Peleg, Department of Infectious Diseases, The Alfred Hospital and Central Clinical School, Monash University, Melbourne, Australia, and David Paterson, University of Queensland Centre for Clinical Research, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia, for the provision of isolates. E.B.H. has received an advisory board honorarium from Nabriva Therapeutics and grant funding from Merck. T.E.B. is a former employee of Nabriva Therapeutics and a current employee of bioM?rieux. All others have no conflicts to disclose.

Publisher Copyright:
Copyright © 2020 American Society for Microbiology. All Rights Reserved.

Keywords

  • Agar dilution
  • Agreement
  • Broth microdilution
  • Error
  • Multidrug resistant
  • Pseudomonas aeruginosa
  • Susceptibility testing

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't

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