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Effect of long-term tetracycline exposure (drinking water additive) on antibiotic-resistance of aerobic gram-negative intestinal flora of rats.

A study was undertaken to determine the effect of 2 years of intermittent administration of tetracycline in drinking water on antibiotic resistance in the aerobic gram-negative enterobacteria of rats in a closed colony. The bacterial isolates examined were resistant to tetracycline and streptomycin. Minimal inhibitory concentrations of tetracycline and streptomycin for intestinal organisms were similar in all of the animals, regardless of whether the animals were sampled while they were given drinking water with added tetracycline or at intervals of 3, 8, and 9 months after the antibiotic was no longer added to the drinking water. Biochemical examination of the isolates from each principal showed that Escherichia coli was the predominant enteric organism. In conjugation experiments, all E coli and Klebsiella pneumoniae isolated transferred tetracycline and streptomycin resistance to an E coli K-12 recipient. Four different strains of rats that had not been treated with tetracycline (controls) were examined for tetracycline resistance. Tetracycline-resistant Proteus mirabilis was isolated from the intestines of these animals. Plasmid-mediated resistance could not be demonstrated. The E coli and P vulgaris isolates from these control animals were susceptible to tetracycline.