JAC-antimicrobial resistance · 2026
Mechanisms of fosfomycin resistance observed in clinical isolates of Escherichia coli from Canada: CANWARD 2007-2022.
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Mataseje Laura F, Lysak Cole, Lerminiaux Nicole, Baxter Melanie, Karlowsky James A, Zhanel George G
Аннотация
BACKGROUND: Oral fosfomycin is commonly prescribed as a single 3 g dose to empirically treat uncomplicated cystitis. This study investigated the mechanisms and frequency of fosfomycin resistance among clinical isolates of Escherichia coli from Canada.
METHODS: In total, 5012 clinical isolates of E. coli collected by the CANWARD surveillance programme from 2007 to 2022 were tested for susceptibility to fosfomycin using the CLSI reference agar dilution method. MICs were interpreted by 2024 CLSI M100 breakpoints. The 19 fosfomycin-resistant (MIC ≥256 mg/L) and 45 fosfomycin-intermediate (MIC 128 mg/L) isolates identified, and 69 fosfomycin-susceptible (MIC ≤1-64 mg/L) control isolates underwent WGS.
RESULTS: In total, 98.7% (4948/5012) of all E. coli isolates tested were fosfomycin-susceptible; 0.4% were fosfomycin-resistant and 0.9% were fosfomycin-intermediate. ST131 accounted for 42.1%, 40.0% and 20.3%, respectively, of fosfomycin-resistant, fosfomycin-intermediate and fosfomycin-susceptible isolates. Six (31.6%) fosfomycin-resistant isolates and one (2.2%) fosfomycin-intermediate isolate carried a fosA gene. All fosA genes were plasmid mediated and all but one fosA-carrying plasmid harboured multiple other antimicrobial resistance genes. A nonsense mutation in, or complete deletion of, one or more genes in the fosfomycin transport systems GlpT and UhpT were observed in 63.2% (37/57) of fosA-negative fosfomycin-resistant and fosfomycin-intermediate isolates but were not detected in any of the 69 fosfomycin-susceptible isolates tested.
CONCLUSIONS: In Canada, the occurrence of mobile fosfomycin resistance determinants (fosA genes) in clinical isolates of E. coli is low (∼0.14% of all isolates). Our results highlight the importance of the functional transporter systems GlpT and UhpT for the in vitro activity of fosfomycin.
METHODS: In total, 5012 clinical isolates of E. coli collected by the CANWARD surveillance programme from 2007 to 2022 were tested for susceptibility to fosfomycin using the CLSI reference agar dilution method. MICs were interpreted by 2024 CLSI M100 breakpoints. The 19 fosfomycin-resistant (MIC ≥256 mg/L) and 45 fosfomycin-intermediate (MIC 128 mg/L) isolates identified, and 69 fosfomycin-susceptible (MIC ≤1-64 mg/L) control isolates underwent WGS.
RESULTS: In total, 98.7% (4948/5012) of all E. coli isolates tested were fosfomycin-susceptible; 0.4% were fosfomycin-resistant and 0.9% were fosfomycin-intermediate. ST131 accounted for 42.1%, 40.0% and 20.3%, respectively, of fosfomycin-resistant, fosfomycin-intermediate and fosfomycin-susceptible isolates. Six (31.6%) fosfomycin-resistant isolates and one (2.2%) fosfomycin-intermediate isolate carried a fosA gene. All fosA genes were plasmid mediated and all but one fosA-carrying plasmid harboured multiple other antimicrobial resistance genes. A nonsense mutation in, or complete deletion of, one or more genes in the fosfomycin transport systems GlpT and UhpT were observed in 63.2% (37/57) of fosA-negative fosfomycin-resistant and fosfomycin-intermediate isolates but were not detected in any of the 69 fosfomycin-susceptible isolates tested.
CONCLUSIONS: In Canada, the occurrence of mobile fosfomycin resistance determinants (fosA genes) in clinical isolates of E. coli is low (∼0.14% of all isolates). Our results highlight the importance of the functional transporter systems GlpT and UhpT for the in vitro activity of fosfomycin.