Animal Model for Determining the No-Effect Level of an Antimicrobial Drug on Drug Resistance in the Lactose-Fermenting Enteric Flora

Abstract

Mature beagles were fed a ground-meal diet containing 0, 2, or 10 μg of oxytetracycline per g for 44 days. The 10-μg/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 μg/g, the level of oxytetracycline that results in increased incidence of antibiotic resistance lies between 2 and 10 μg/g in this dog model. Rats and hamsters fed diets containing oxytetracycline (10 μg/g or greater) or dihydrostreptomycin (10 μg/g), and provided suspensions of drug-susceptible Escherichia coli , did not develop a population of antibiotic-resistant organisms.

Effect of Subtherapeutic Administration of Antibiotics on the Prevalence of Antibiotic-Resistant Escherichia coli Bacteria in Feedlot Cattle

“…Thus, it is possible that 11 ppm was below the selective concentration window required to confer tetracycline resistance (42). Others have proposed that similar concentrations of tetracycline, as applied in the TET treatment, should not select for tetracycline-resistant E. coli (49). In contrast, the concentration of chlortetracycline in the diets supplemented with TET-SUL may have been sufficient to confer tetracycline resistance and promote ampicillin resistance as well.…”

Effect of various oral dose levels of a trimethoprim/sulphadiazine mixture on Bordetella bronchiseptica infection and on the proliferation of trimethoprim-resistant faecal coliforms in pigs

“…Few reports appear to have been made of the relationship between dose level of antibacterial drugs and proliferation of resistant enteric coliforms, but Rollins et al (1975) found that the feeding of 10 lg oxytetracycline/g of dry meal to beagles resulted in the appearance of a high proportion of resistant coliforms, whereas 2 ,ug/g had no such effect. These observations are similar to those reported above for TMP/SDZ, suggesting that high oral doses of an antibacterial drug are more likely to induce resistance in enteric coliforms than lower doses, presumably because of the exertion of greater selective pressure in favour of any resistant organisms present.…”

An evaluation of methods to assess the effect of antimicrobial residues on the human gut flora

“…Attempts were made to provide E. coli cells continuously in the drinking water of rats, or to expose the rats to an environment highly contaminated with E. coli. These rodent models proved to be unsatisfactory for determining the no-effect level of an antimicrobial on the gut flora (Rollins et al, 1975). * The feeding of certain antimicrobial as feed additives to chickens, pigs or calves result in a population of resistant fecal E. coli.…”

“…Therapeutic treatments or inter-group cross contaminations are difficult to avoid in farm animals studies (Linton et al, 1975). Moreover, natural changes in bacterial populations in the gut of chicken and pig interfere with any possible drug effect (Linton et al, 1985) * Rollins et al (1975), and Gaines et al (1978Gaines et al ( , 1980 fed groups of 5-7 beagle dogs for 35-57 d with residue doses of oxytetracycline, dihydrostreptomycin, penicillin or virginiamycin. Total and resistant coliforms were counted in 5 to 10 samples from each animal, and compared to levels in control untreated dogs.…”