Therapeutic Effects of Antibiotics against Enterohemorrhagic Escherichia coli (EHEC) O157: H7 (O157)

Infection: In Vivo Analysis Using Germfree Mice

Abstract

Though O157 can cause a life-threatening diseases, the therapeutic protocol using antibiotics for the infection is still controversial. Main reasons for hesitating the uses of antibiotics for the infection is their possibility to enhance the release of verotoxins (VT). We have recently established the mouse model of O157 infection using germfree mice. Using this animal model of O157 infection, weexamined therapeutic efficacy of antibiotics. Fosfomycin (FOM) and norfloxacin (NFLX) were selected for in vivo examination, because of their lower MIC under anaerobic condition (MIC: FOM=0.78; NFLX=0.10μg/ml) than those of the other antibiotics including kanamycin, doxycycline, minocycline, choramphenicol, cefaclor and ampicilin. When germfree BALB/c mice were orally infected with 1×10⁵CFU of O157 (clinically-isolated strain, TI001) at day 0, all mice died at 8 to 9 d after the infection. Oral treatment of the mice with FOM (500mg/kg/d, twice a day) or NFLX (50 mg/kg/d, twice a day) everyday for 5 days starting at 3 hr after the infection significantly improved the survival rate from 0% to 83.3%, and 100%, respectively. VT could not be detected in the feces of the mice in either groups, suggesting that neither of these antibiotics enhanced the release of VT . Interestingly, when FOM treatment was started at 3, 6, 12 or 24 hr after the infection, the survival rate was 100%, 100%, 0% and 0%, respectively. Thus, in conclusion, FOM and NFLX are both useful as the therapeutic agents for 0157 infection. However, the treatment should be started in the early phase after the infection.