Antibiotics that do not cause Shiga-toxin mediated disease in C. rodentium φstx2d-infected mice and their effect on the intestinal microbiota

Enterohaemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes disease ranging from watery diarrhoea to acute renal failure. Disease progression is attributed to the production of Shiga toxins (Stx). Treatment of EHEC infections remains supportive, and the use of antibiotics is highly controversial as they can induce Shiga toxin expression and may, therefore, increase the risk of haemolytic-uraemic syndrome development. While Stx induction has been assessed in vitro, the in vivo confirmation was hampered by the lack of an adequate mouse model. Introduction of a lysogenic phage encoding stx2d into the mouse pathogen C. rodentium, however, created a strain that mimics a human EHEC infection in mice.

Infecting mice with C. rodentium φstx2d, we investigated the effects of antibiotic treatment on host pathology. Using the fluoroquinolone enrofloxacin known to induce Shiga toxin production, we observed that the mice showed rapid weight loss after treatment onset even though the infection was cleared. Furthermore, the kidney damage in these mice was comparable to that observed for infected but untreated mice. Several tested antibiotics, however, could clear the infection without resulting in kidney damage. These included ampicillin, rifampicin, and tetracycline. Unfortunately, the antibiotics that most efficiently cleared the C. rodentium φstx2d infection also had the most detrimental effect on the faecal microbiota, causing a severe decrease in microbiota diversity.

Our data suggest that while some antibiotics increase Stx production and release, others may well be used as treatment options, especially during outbreaks. However, great care needs to be taken when using these antibiotics, as one has to weigh the harmful effects of both the infection and the antibiosis.