Effective Interventions to Prevent Emergence and Dissemination of Antimicrobial Resistance at the Population, Animal, and Microbial Levels

<p>NON-TECHNICAL SUMMARY:<br/> The emergence and dissemination of antimicrobial-resistant zoonotic pathogens in livestock populations is driven by complex interactions of production systems management, antimicrobial use in individual animals, and the animal's enteric flora. This suggests that effective interventions may be applied at various levels of organization including the production system, the individual animal, and the bacterial flora of food animals. We propose to investigate mitigation strategies to prevent the emergence and dissemination of antimicrobial resistant enteric bacteria and resistance genes of animal and public health concern. We will focus on extended-spectrum cephalosporin and fluoroquinolone resistance because of the critical importance of these antimicrobials in both veterinary and human medicine. Our central hypothesis is that effective
interventions to mitigate the dissemination of pathogens resistant to critically important antimicrobial drugs in livestock populations can be identified at the levels of the production system, individual animal, and the bacterial flora present in animals. Our objectives are to 1. Establish the effectiveness of specific animal-level mitigation strategies that can be applied to herds of food animals that impact the emergence, maintenance, and dissemination of antimicrobial resistant pathogens and resistance genes, 2. Estimate the effectiveness of population-level mitigation strategies by measuring the impact of regulatory restrictions on the emergence and dissemination of antimicrobial resistance, 3. Identify potential bacterial flora-level mitigation strategies by describing and understanding the competition of multiple bacterial strains for the same ecological niche in the microbial
flora, and 4. Disseminate knowledge of specific antimicrobial resistance mitigation strategies to veterinarians and their clients that produce food animals. We expect to identify effective new strategies for mitigation of antimicrobial resistance in livestock populations which in turn will protect animal health and agricultural productivity while improving food safety and the public health.
<p>APPROACH:<br/> Our overall approach will be to generate scientifically valid data to evaluate interventions applied at various levels of organization including the animal (herd), the population (regulatory), and the microbial flora (bacteria). We will accomplish our first objective by testing the impact of replacing ceftiofur antimicrobial therapy for metritis in dairy cows with a non-antimicrobial treatment on the presence and quantity of extended-spectrum cephalosporin resistance genes in the enteric commensal flora. In addition, we will test the impact of removing exposure to antimicrobials present in waste milk fed to dairy calves on resistance genes in their enteric flora. We will accomplish our second objective to test population-level regulatory interventions by comparing the evolution of extended-spectrum cephalosporin and fluoroquinolone resistance in Salmonella
recovered from finishing swine barns and dairy herds since the relatively recent approval of enrofloxicin for use in these production systems with very restrictive label applications compared to the much less restrictive label for ceftiofur use. We will accomplish our third objective to identify potential microbial-level interventions by describing the competition of multiple bacterial strains for the same ecological niche in the microbial flora in order to identify candidate susceptible strains that may be able to fully displace resistant strains and replace them in their ecological niche. We will also develop and integrated outreach extension program to educate food animal veterinarians and their livestock producer clients regarding appropriate antimicrobial use and effective mitigation strategies to prevent the emergence and dissemination of antimicrobial resistance.