Animal model for determining the no-effect level of an antimicrobial drug on drug resistance in the lactose-fermenting enteric flora.

Mature beagles were fed a ground-meal diet containing 0, 2, or 10 mug of oxytetracycline per g for 44 days. The 10-mug/g diet resulted in a shift from a predominantly drug-susceptible population of enteric lactose-fermenting organisms to a multiply antibiotic-resistant population which peaked at 78% resistant organisms. Since a shift to drug-resistant organisms did not occur in the group fed 2 mug/g, the level of oxytetracycline that results in increased incidence of antibiotic resistance lies between 2 and 10 mug/g in this dog model. Rats and hamsters fed diets containing oxytetracycline (10 mug/g or greater) or dihydrostreptomycin (10 mug/g), and provided suspensions of drug-susceptible Escherichia coli, did not develop a population of antibiotic-resistant organisms.