Therapeutic effect of fosfomycin against interstinal infection with Escherichia coli O157: H7 in a mouse model

The therapeutic effect of fosfomycin at a large oral dose against intestinal infection with Escherichia coli O157: H7 was investigated in a mouse model previously described. Three ICR strain (IQI, germ free) mice aged 5 weeks were challenged orally with a verotoxin-producing strain NK2 of E. coli O157: H7. The high levels of viable cells, 3.0 x 10¹⁰-3.4 x 10⁸ CFU/g, were excreted into the feces of the untreated mice for 3-10 days after bacterial challenge. Fosfomycin was given at an oral dose of 600 mg/kg twice a day for 6 days to 3 mice infected with E. coli O157: H7, beginning 3 days after the challenge, to investigate changes in viable cell counts and to measure fecal concentrations of fosfomycin. Results were that the viable cells decreased markedly, (from about 10¹⁰ CFU/g before dosing) to 10³- 10⁴ CFU/g on day 1 of dosing, and no viable cells were detected in the feces from day 2 of dosing onwards. During the period, no verotoxin was detected in fecal samples collected from all 6 test mice (including 3 control mice). Concentrations of fosfomycin in the feces after dosing were 34.6-47.4 μg/g in all the mice on day i of dosing, and 62.4 and 131.1 μg/g in 2 of the mice on day 6 after dosing, but nondetectable otherwise. These results suggested that a marked decrease in viable cells without the liberation of verotoxin was observed in the feces of infected mice after fosfomycin was given orally in a massive dose.