Antimicrobials in Animal Production

Antimicrobials for Controlling Infectious Disorders

• Antimicrobial use in animal production is common practice to minimize microbial stressors. Antimicrobials are categorized as antibiotics, antifungals, antivirals, and antiparasitics.
• Antibiotics are most commonly used historically. In 2015, two-thirds of global antibiotic production was used in animal husbandry.
• Global livestock antibiotic use (cattle, sheep, chickens, and pigs) in 2020 was 99,502 tonnes, projected to increase by 8% by 2030.
• Top 5 user countries are China, Brazil, India, USA, and Australia.
• Global aquaculture antibiotic use in 2017 was 11,308 tonnes, projected to increase by 33% by 2030.
• Top user countries include China, India, Indonesia, and Vietnam.
• Antibiotics excreted in animal waste (feces and urine) can impact the environment, at rates of 30-90%.

Driving Forces Behind Antimicrobial Usage

• Producer-driven increasing livestock productivity
• Consumer-driven increasing product quality
• Consumer and food processor-driven improvements in product uniformity
• Consumer and producer-driven improvements in animal welfare through reduced disease
• Society-driven reducing risks of zoonosis

Increasing Livestock Productivity with Antimicrobials

• Antimicrobials boost productivity via growth promotion and reduced disease-related losses.
• Sub-therapeutic concentrations (2.5-125 ppm) of antimicrobials in animal feed/water are considered antimicrobial growth promoters (AGPs).
• AGPs were first used in 1946, and approved in 1951 by the US FDA.
• AGPs are most effective in improving growth of pigs and poultry under poor hygiene early in life, crucial for neuroendocrine immune system development.
• Effectiveness of AGPs is less certain with improved housing, feed, and water quality; usage may reduce producer profits.

Summary of AGP Usage in Canadian Livestock

• Summary of AGPs previously used in Canadian livestock production is provided. (Slide 4)

AGP Mechanisms of Action

• Exact mechanisms of antimicrobial action on animal growth are yet to be determined, but vary among antimicrobials.

Interactions of Antimicrobials with Gut Microbiota

• Antimicrobial effects can induce subtle changes in gut microbial populations, which optimise nutrient availability, control pathogens, and support a healthy immune response without becoming overwhelming.
• Reduction in microbial competition for nutrients or reduction in microbial metabolite production that inhibit growth is also a possible outcome.
• Therapeutic levels of certain antimicrobials can manage gut inflammation, regulate host immune response, (especially T cell sub-populations), and improve innate immune response.
• Inflammation may be triggered or made worse by some pathogens (e.g., viruses) as a strategy to avoid immune detection.
• The body directing energy towards immune-related processes results in reduction in growth, loss of appetite, and muscle breakdowns.

2016 US Antimicrobials Usage

• Tetracyclines (70%), penicillins (10%), macrolides (7%), sulfas (4%), and aminoglycosides (4%) were the medically important antimicrobials used in food-producing animals in the US between 2015-2016.
• Tetracyclines (42%) and ionophores (33%) are the most commonly used antimicrobials in the US.
• Usage by species (cattle, swine, turkey, chicken) is provided. (Slide 8)
• Poultry antibiotic use has been declining, while the use of ionophores has been increasing.

Antimicrobials, Tolerance Levels, Withdrawal Times

• US and EU approved antimicrobials, corresponding tolerance levels and withdrawal times for drug residues in different tissues are available. (Slide 9)

Consequences of Antimicrobial Usage

• Antimicrobial usage in livestock leads to exposure of consumers to bioactive drug residues (i.e., allergies, gut microbiota), negatively affect environment (algae, invertebrates, and fish), and potentially lead to antimicrobial resistant (AMR) pathogens, which can be transferred between species.
• AMR in microbes refers to the ability to be unaffected by the antimicrobial growth inhibitors.

Mcr-1 and Resistance to Colistin

• The mcr-1 gene, discovered in 2015, confers resistance to colistin, a last-resort antibiotic.
• Colistin usage in animals has been banned in parts of China, despite mcr-1 presence in livestock and pets worldwide.
• Horizontal transfer of plasmids containing mcr-1 has occurred, and is found in other species such as Salmonella.

Aquaculture and Antimicrobial Resistance

• AMR levels in fish bacterial pathogens correlate with those in humans.

Factors Contributing to Antimicrobial Resistance Development

• The misuse of antimicrobials (higher doses than needed, use for prevention, use in sub-therapeutic levels) leads to human exposure and development of AMR in environmental microbes, including pathogens for human or animal health.
• Poor quality or expired antimicrobials reduce therapeutic dosing and promote resistance.
• Antimicrobial residues in animal waste and contaminated environments (e.g., soil, water, and aquatic environments in aquaculture) can spread AMR.
• Heavy metals and biocides (e.g., disinfectants, solvents) can promote AMR.
• Use of nitrogen fertilizers can contribute to the growth of AMR microbes.

Strategies to Reduce Antimicrobial Resistance

• Limiting/stopping antibiotics for growth promotion
• Reducing overuse of antibiotics
• Providing access to non-medicated feed options
• Implementing strategies for stricter regulations and monitoring
• Developing new antimicrobial treatment strategies
• Developing new alternative approaches (e.g., bacteriophage, gene editing, microbiome modification, etc.)