Susceptibility of Clinical Isolates of Escherichia coli to Fosfomycin as Measured by Four In Vitro Testing Methods

Clinical isolates of ( = 554) were tested against fosfomycin using agar dilution, disk diffusion, and Etest. Agar dilution (reference method) identified few isolates with fosfomycin MICs of 64 ( = 3), 128 ( = 4), and ≥256 μg/ml ( = 2). Applying CLSI (M100, 2020) and EUCAST (v. 10.0, 2020) breakpoint...

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Published in:Journal of clinical microbiology 2020-09, Vol.58 (10)
Main Authors: Karlowsky, James A, Lagacé-Wiens, Philippe R S, Laing, Nancy M, Baxter, Melanie R, Adam, Heather J, Zhanel, George G
Format: Article
Language:English
Subjects:
Bacteriology
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Summary:Clinical isolates of ( = 554) were tested against fosfomycin using agar dilution, disk diffusion, and Etest. Agar dilution (reference method) identified few isolates with fosfomycin MICs of 64 ( = 3), 128 ( = 4), and ≥256 μg/ml ( = 2). Applying CLSI (M100, 2020) and EUCAST (v. 10.0, 2020) breakpoints, 98.9% and 98.4% (agar dilution), 99.3% and 99.1% (disk diffusion), and 99.1% and 98.9% (Etest) of isolates were fosfomycin susceptible, respectively. Essential agreement (agar dilution versus Etest) was low (40.8%); 59.3% (131/221) of isolates with agar dilution MICs of 2 to 128 μg/ml tested 2 to 4 doubling dilutions lower by Etest. Applying CLSI breakpoints, categorical agreement was >99% for both disk diffusion and Etest; no major errors (MEs) or very major errors (VMEs) were identified, and rates of minor errors (mEs) were 99% and no MEs for both disk diffusion and Etest; however, VMEs occurred at unacceptable rates of 44.4% (disk diffusion) and 33.3% (Etest). All isolates with agar dilution MICs of ≥32 μg/ml ( = 12) and a subset of isolates with MICs of ≤16 μg/ml ( = 49) were also tested using the Vitek 2 AST-N391 card and generated fosfomycin MICs 1 to ≥3 doubling dilutions lower than agar dilution for 11/12 isolates with agar dilution MICs of ≥32 μg/ml. We conclude that performing fosfomycin disk diffusion or Etest on urinary isolates of and interpreting results using CLSI breakpoints reliably identified fosfomycin-susceptible isolates regardless of differences in endpoint reading criteria. EUCAST breakpoints generated excessive rates of VMEs for our isolate collection of high fosfomycin susceptibility.
ISSN:0095-1137
1098-660X
DOI:10.1128/JCM.01306-20