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Use of Fosfomycin Etest® to Determine In Vitro Susceptibility of Clinical Isolates of Enterobacterales Other Than Escherichia coli , Non-Fermenting Gram-Negative Bacilli, and Gram-positive Cocci

James A. Karlowsky, Melanie R. Baxter, Alyssa R. Golden, Heather J. Adam, , Philippe R. S. Lagacé-Wiens, George G. Zhanel

Abstract: Clinical isolates of Enterobacterales other than Escherichia coli (EOTEC), non-fermenting Gram-negative bacilli, and Gram-positive cocci were tested for susceptibility to fosfomycin using Etest ® and reference agar dilution. Applying EUCAST (v. 11.0, 2021) intravenous fosfomycin breakpoints, Etest ® MICs for EOTEC showed essential agreement (EA), categorical agreement (CA), major error (ME), and very major error (VME) rates of 70.4%, 88.4%, 4.1%, and 32.1%, respectively. No species of EOTEC tested with acceptable rates for all of EA (≥90%), CA (≥90%), ME (≤3%), and VME (≤3%). Etest ® MICs for Enterococcus faecalis , interpreted using CLSI oral/urine criteria (M100, 2021), showed EA, CA, minor error, ME, and VME rates of 98.5%, 81.2%, 18.8%, 0%, and 0%. Against Staphylococcus aureus , EA, CA, and ME rates were 84.1%, 98.7%, and 1.3% (EUCAST intravenous criteria). S. aureus isolates with fosfomycin MICs >32 μg/ml (resistant) were not identified by agar dilution. We conclude performing fosfomycin Etest ® on isolates of S. aureus will reliably identify fosfomycin-susceptible isolates with low, acceptable rates of MEs and VMEs. Testing of urinary isolates of E. faecalis by Etest ® is associated with an unacceptably high rate of minor errors (18.8%) but low, acceptable rates of MEs and VMEs when results are interpreted using CLSI criteria. Isolates of EOTEC tested by Etest ® with resulting MICs interpreted by EUCAST criteria were associated with an unacceptably high VME rate (32.1%). In vitro testing of clinical isolates beyond E. coli , E. faecalis , and S. aureus to determine susceptibility to fosfomycin is problematic with current methods and breakpoints.
Keywords: Etest / fosfomycin / EUCAST / EOTEC / Gram / VME / Clinical Isolates / faecalis

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