Minimum antibiotic levels for selecting a resistance plasmid in a gnotobiotic animal model

The minimum antibiotic concentrations for selecting an R plasmid in vivo were determined in germfree mice colonized by two isogenic strains of Escherichia coli, one of which carried an R plasmid. Seventy groups of three gnotobiotic mice were given low doses of ampicillin, colistin, flumequin, gentamicin, tetracycline, or streptomycin via drinking water for 2 weeks. The equilibrium between susceptible and resistant populations of bacteria was monitored daily in feces and compared with that of control mice given pure water. This model yielded reproducible data, and dose and response were strongly correlated. The minimum selecting doses ranged from 0.9 to 12.8 micrograms/ml of water, depending on the antibiotic and the R plasmid. The use of mathematical models and complementary in vitro experiments accounted for the effect of the low antibiotic levels.