Impact of disease in dairy cows on ceftiofur pharmacokinetics, withdrawal times and emergence of antimicrobial resistance

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Gorden, Patrick
Major Professor
Johann F. Coetzee
Ronald W. Griffith
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Veterinary Microbiology and Preventive Medicine
Our faculty promote the understanding of causes of infectious disease in animals and the mechanisms by which diseases develop at the organismal, cellular and molecular levels. Veterinary microbiology also includes research on the interaction of pathogenic and symbiotic microbes with their hosts and the host response to infection.
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Producing safe and wholesome food is a priority of animal agriculture in order to maintain consumer confidence in the products produced by the animal agriculture industries. Antimicrobial residues and antimicrobial resistant organisms are two of the most important concerns of consumers regarding food safety. Withholding periods are in place to minimize the risk of antimicrobial residues being present in food. However, these withholding periods are established on healthy animals, not clinically ill animals. Additionally, there is no such withholding period in place to minimize the risk of transporting antimicrobial resistant organisms through food following treatment, although it has been proposed. The first objective of this dissertation was to investigate the impact of clinical disease on the pharmacokinetics of ceftiofur. The second objective was to investigate changes in the fecal microbiota following drug therapy. The results of this work demonstrate the volume of distribution is increased in diseased animals and area under the concentration curve is decreased. Additionally, the mean elimination half-life can be significantly different. In both studies involving clinical disease, at least one animal in each group had an elimination half-life that was nearly twice as long as the mean of the control group. No animals were found to have violative drug residues present in tissues following observation of the labeled withholding time. Fecal Escherichia coli populations transiently decreased following therapy with ceftiofur and ceftiofur resistant populations were significantly different than untreated controls. There was a tendency towards a significantly higher ceftiofur resistant E. coli population in diseased animals treated with ceftiofur versus healthy animals treated controls. By 14 days following therapy, total and resistant E. coli populations returned to pre-treatment levels. E. coli isolates that were resistant to ceftiofur were also cross-resistant to ampicillin and ceftriaxone. Additionally, 64.3% of the resistant isolates were also resistant to tetracycline. The à  -lactamase gene blaCTX-M was most commonly found in ceftiofur resistant isolates but mechanism for ceftiofur resistance was not identified in 55.8% of the ceftiofur resistant isolates. Isolates that were determined to be phenotypically ceftiofur cross-resistant were resistant to 4.72 while isolates that were ceftiofur sensitive were cross-resistant to 1.1 antimicrobials. The current study suggests that changes in bacterial populations following clinical disease are not different from those of healthy cows treated with ceftiofur. Observation of the established drug withholding period following treatment with ceftiofur crystalline free acid minimizes the risk of transferring fecal isolates harboring antimicrobial resistance to the public.

Sun Jan 01 00:00:00 UTC 2017