A mouse model of Escherichia coli .O157: H7 infection for evaluation of antibacterial drugs - In vivo release of verotoxins and toxic effect on mice

IQI mice (ICR, 5 weeks old) were orally challenged with verotoxin-producing strains of Escherichia coli O157: H7 NK2 or R29. The viable cells, at 10 ¹⁰-10 ¹¹ CFU/g, excreted into the feces were collected from the non-treated mice for 1-6 days after infections with both strains, which indicates stable inoculation in their intestinal tracts. No mice died in the non-treated groups during or after the dosing period. Norfloxacin was given orally at a dose of 3 mg/kg twice/day for 6 days to three mice each which were infected with NK2 or R29 strains. VT2 of 625-2,500 ng/g was found in the feces of the infected mice for 15 hours after two doses on the first day of norfloxacin dosing, and large amounts of VT1 (1,250-5,000 ng/g) and VT2 (40,000 ng/g) were also found in the feces for 15 hours after dosing on the second day. Although a marked decrease in the viable cell count was found in the feces of the mice given norfloxacin, all the mice died within 4-5 days after onset. On the other hand, when fosfomycin was given to the infected mice at a dose of 25 mg/kg twice/day for 6 days, no verotoxins were found in any feces of the mice and no mice died of infection with either E. coli O157: H7 NK2 or R29. Very high concentrations of VT2 were found in the contents of the lower intestines of mice which died after norfloxacin dosing. Bleeding was detected in the intestines of 4 of the 6 dead mice, and a positive occult reaction was observed in feces of the other 2 mice. No such changes were observed in the mice given fosfomycin.This intestinal infection model in mice infected with E. coli O157: H7 may be useful for evaluating the in vivo production or liberation of verotoxins by antibacterial drugs and their toxic effects on mice infected with this bacterial strain.