Influence of Antibiotics Administered in Therapeutic Doses on Colonisation Resistance Against Enteric Pathogens in Mice

Colonisation resistance against oral challenge with Salmonella typhimurium, Shigella flexneri and enterotoxigenic Escherichia coli (ETEC) was determined using untreated mice and mice pre-treated with therapeutic doses of either amoxicillin, chloramphenicol, erythromycin, penicillin or trimethoprim-sulfamethoxazole (TMS), or with streptomycin, administered in high dose. The effects of these antibiotics on the pH levels and volatile fatty acid (VFA) concentrations of caecal contents were also determined. Only streptomycin treatment altered colonisation resistance. The incidence of caecal colonisation by all three pathogens and their populations were significantly greater in streptomycin treated than untreated mice. Except for an increase in the incidence of colonisation by ETEC after erythromycin treatment, none of the antibiotics, administered in therapeutic doses, produced significant effects on colonisation resistance. Relative to untreated mice, streptomycin treatment caused a statistically significant decrease in total caecal VFA's, from 60.80 μeq/g to 21.63 μeq/g, and a significant increase in pH from 6.75 to 7.04. Treatment with TMS caused an increase in total caecal VFA to 91.18 μeq/g. Treatment with the other antibiotics failed to produce significant changes in total caecal VFA's and, with the exception of chloramphenicol treatment resulting in a pH of 7, in caecal pH levels. All of the pathogens were sensitive to the presence of VFA in nutrient broth. In every case, their populations, after 12 h incubation, were greatest in broth containing 21.63 μeq/ml VFA adjusted to pH 7.04, simulating conditions in the caecum of streptomycin treated mice, and were smallest in broth containing 91.18 μeq/ml VFA adjusted to pH 6.74, simulating conditions in the caecum of TMS treated mice. Despite the suppressive effects of conditions simulating TMS treatment in vitro , mice treated with this combination of antibiotics were no more resistant to colonisation with the pathogens than were untreated mice. The results demonstrate that antibiotics, administered in therapeutic doses, have little effect on colonisation resistance against enteric pathogens in mice and suggest that a similar situation may exist in humans. Keywords: Antibiotics; Colonisation resistance; Mice.