Antibiotic Therapy in the Treatment of E. coli O157:H7

Escherichia coli O157:H7 causes an estimated 73,000 of food borne illness annually. Varying levels of disease severity exist and include diarrhea, bloody diarrhea, and hemolytic uremic syndrome which can result in kidney damage or death. E. coli O157:H7 produces Shiga toxins 1 and/or 2, although it is Shiga toxin 2 that is linked to severe disease. Currently, a Shiga toxin-producing isolate will yield a positive diagnostic result, regardless of which Shiga toxin variant is produced. We have developed an ELISA that can differentiate between Shiga toxin 1 and Shiga toxin 2 in the presence of fecal material, and if used in the clinical setting, can increase the accuracy of prognosis for a patient infected with E. coli O157:H7. Epidemiological studies have suggested that antibiotics may be linked to HUS development. As such, we have completed an extensive study to determine which, if any, antibiotics are safe for the treatment of E. coli O157:H7. The data suggest that antibiotic-mediated Shiga toxin induction or reduction is based on the mechanism. Antibiotics that target DNA increase Shiga toxin production while protein synthesis inhibitors decrease Shiga toxin production. Human intestinal E. coli have been shown to amplify Shiga toxin. Our data suggest that protein synthesis inhibitors may be effective, even if the patient harbors a Shiga toxin-amplifying isolate, provided that the commensal isolate is susceptible to the antibiotic. Conversely, antibiotics would likely be of no benefit if the Shiga toxin-amplifier is resistant to the antibiotic. Future studies should focus on characterizing the flora of HUS patients, and examining antibiotic treatments within the context of these strains.