Proposal for effective treatment of Shiga toxin-producing Escherichia coli infection in mice

• Stx2d-producing (B2F1) and Stx2c-producing (E32511) Escherichia coli strain were used.
• The Chinese medicine Daio alone inhibited the colonization of B2F1 in the mouse intestine.
• Only azithromycin (AZM) alone did not completely eliminate E32511 in mouse feces.
• We reduced E32511 in mouse feces by treatment with the combination of AZM and Daio.
• We developed a new therapy using a combination of AZM and Daio.

Previously, we reported that minocycline, kanamycin and norfloxacin improved the survival rate in the E32511 model that we developed (FEMS Immunol Med Microbiol 26, 101–108, 1999), but fosfomycin did not. In this study, we investigated the effectiveness of azithromycin (AZM) against Stx2d-producing EHEC O91:H21 strain B2F1 or Stx2c-producing Escherichia coli strain E32511 treated with mitomycin C in vivo. Recently, we reported the effectiveness of AZM in our model and AZM strongly inhibited the release of Stx2c from E32511 in vitro (PLOS ONE e58959, 2013). However, it was very difficult to completely eliminate E32511 in the mouse feces by treatment with AZM alone. In this report, only AZM or Daio effectively promoted survival of mice infected with B2F1 compared to untreated mice. Furthermore, Daio inhibited the colonization of GFP-expressing B2F1 in the mouse intestine. Similarly, a combination of AZM and Daio in the E32511-infected mice reduced E32511 in the mouse feces and significantly improved survival.