Research »   Antimicrobial Resistance

Antimicrobial Resistance

Antimicrobial resistance occurs naturally when the genetic make-up of microbes is altered in a manner that makes them no longer susceptible to antimicrobials designed to kill them or prevent their growth. In Canada, surveillance indicates that resistance levels in cattle are extremely low and have not increased over time. Research and surveillance evidence suggests that eliminating antimicrobial use in beef production will have clear negative health consequences for cattle with no obvious benefit for human health.


Definitions

Antibiotic: an antimicrobial substance produced by a microorganism (or a synthetic version) that can kill or prevent the growth of another microorganism. In human and veterinary medicine, antibiotics are used to treat bacterial infections.

Antimicrobial: a substance that can destroy or prevent the growth of microorganisms. There are many different types of antimicrobial substances, including antibiotics, anti-protozoals (e.g. ionophores for coccidiosis), alcohol, soap and bleach.

All antibiotics are antimicrobials, but not all antimicrobials are antibiotics. The two terms are often used interchangeably.

Function of Antimicrobials

Some antimicrobials are naturally produced by microorganisms. Imagine that two types of microbes share the same environment and rely on the same nutrient source to exist. Microbe A will have a competitive advantage if it can produce and excrete an antimicrobial that inhibits or kills microbe B.

Antimicrobials are used in human and veterinary medicine for the same reasons. Using an antimicrobial to target specific microbial pathogens is an effective way to combat infectious disease, especially when effective vaccines are not available.

Antimicrobials harm or kill their target microbe by damaging or blocking specific structural features (e.g. the cell wall or a cell surface receptor) or metabolic functions. A genetic mutation or the acquisition of gene by the target microbe can change structural features or metabolic processes to resulting in the microbe and its offspring being no longer susceptible to that antimicrobial, or other antimicrobials that kill or prevent growth in the same manner.

Mutation of Microbes

Antimicrobial resistance occurs naturally and is not caused by antimicrobial use. If the antimicrobial is used when an antimicrobial resistant disease-causing microbe (pathogen) is present, the antimicrobial resistant pathogen will have a competitive advantage over its susceptible cousins.

It is important to recognize that mutation is not caused by the presence of an antimicrobial

Natural antimicrobial resistance

If the antimicrobial continues to be used, the resistant pathogens will survive, reproduce and become more common, while the susceptible pathogens will gradually become scarcer. In this case, the antimicrobial will become less effective, and the animal will not respond to continued treatment with the same antimicrobial, even if the dose is increased. In this case, the veterinarian or doctor may switch to an antimicrobial from a different class.

Classes of Antimicrobials

Antimicrobials are divided into four classes based on their importance in human medicine.

  • Antimicrobial use humans vs animals vs feedlot cattleAntimicrobials classified as ‘Very High Importance’ are used to treat very serious human infections.
  • ‘High Importance’ antimicrobials are of intermediate concern in human medicine.
  • ‘Medium Importance’ drugs are rarely used to treat serious human health issues. For example, tetracycline used to treat acne is classified as Medium Importance.
  • Antimicrobials of ‘Low Importance’, like ionophores, are not used in human medicine at all.

Antimicrobials from each category are approved for use in beef cattle, but drugs classified as Very High Importance are very seldom used.

 

Concerns in Cattle Production

Antimicrobial resistance is a concern in livestock production for two reasons:

  1. If pathogens develop resistance, the antimicrobials will stop working, animals will not respond to treatment, performance will suffer and death losses may increase.
  2. Antimicrobial resistant livestock pathogens may be able to pass their resistance on to human pathogens. This would result in antimicrobial drugs not being as effective in treating human infections as well.

Concerns in Public Health

The greatest concern is with antimicrobials that are of Very High Importance in human medicine, but that are also used in livestock. These are drugs of last resort in human medicine; they are used for infections that are not responding to lesser drugs, and for which there are no other alternatives. If the Very High Importance drugs fail to work, doctors have no other options.

The use of all antimicrobials in veterinary medicine are approved and regulated by Health Canada.

The Canadian beef industry has supported a number of research projects studying this issue since the late 1990’s. One such study funded through the Beef Cattle Research Council (BCRC) found that drugs that are most important for human health are rarely used by the Canadian beef industry. Conversely, the drugs that are used most widely by the Canadian beef industry are never used in human medicine. These results are summarized in the Table below.

Ionophores (classified as 'low importance' in human medicine) are often erroneously included in discussions about the concern of antimicrobial use in livestock and the potential link to antimicrobial resistance in humans. Ionophores are not used in human medicine, and have a very different mode of action than other antibiotics. This leads to the conclusion that ionophores do not lead to cross-resistance to antibiotics of importance in human medicine.

Surveillance of Antimicrobial Resistance in Beef Cattle

The Public Health Agency of Canada has developed the Canadian Integrated Program for Antimicrobial Resistance Surveillance(CIPARS) to monitor antimicrobial resistance in humans and livestock, and retail meat. To date, the CIPARS has seen that resistance to drugs of Very High Importance is below 2% in bacteria isolated from Canadian cattle or retail beef, and has remained stable for 10 years.

This low level of resistance is probably because drugs of Very High Importance are very rarely used; drugs of last resort in human medicine are also drugs of last resort in bovine medicine.

Research and surveillance evidence suggests that eliminating antimicrobial use in beef production will have clear negative health consequences for cattle with no obvious benefit for human health.

The potential link between antimicrobial use in cattle production and antimicrobial resistance in human medicine has been very difficult to prove or disprove. One study funded by the Canada-Alberta Beef Industry Development Fund found that bacteria isolated from feedlot staff who worked both with sick cattle and the drugs themselves had antimicrobial resistance levels that were no higher (and were lower in many cases) than in bacteria collected from human health labs.

Misconceptions in Antimicrobial Use and Resistance in Livestock

Livestock industries are also often criticized due to misinformation and misunderstanding around the use of antimicrobials to promote growth.

Antimicrobials in cattle feed

In some cases, the method of drug delivery is confused with why it is being used. For example, when a drug is fed to an animal, rather than injected, an incorrect assumption may be made that the purpose of the fed medication is to promote growth. In fact, if a large number of animals need to be treated on a daily basis for a period of time, it is much safer and less stressful to deliver the drug through feed or water than to handle each animal individually and repeatedly for daily drug injections.

Water or feed may be used to deliver oxytetracycline and chlortetracycline to feeder calves at high risk of respiratory disease. Similarly, oral tetracycline may be delivered to teenagers to treat acne, not to make them grow faster.

A poor appetite is a common sign of respiratory disease in cattle. Keeping animals healthy keeps them eating and growing, which may also contribute to the confusion between antimicrobial use for health purposes and growth promotion.

Using metaphylactics in cattle

Metaphylaxis may be used to prevent respiratory disease in high-risk (lightweight, freshly-weaned, auction mart derived) calves. Newly arrived feedlot calves may be stressed, depending on whether they have been recently weaned, how far they’ve been transported, and whether they have been adapted to dry feed. Stress can impair immune function. Since effective vaccines are not available for all of the respiratory pathogens that cause illness in feedlot cattle, metaphylactic antimicrobial treatment may be used to prevent disease for the first few weeks in the feedlot until the calves have adapted and overcome the stresses that predispose them to respiratory diseases.

Metaphylactic treatments that use drugs of Low or Medium Importance in human medicine to effectively prevent disease in cattle reduce the need to use more powerful antimicrobial drugs of Very High Importance to treat and cure disease once the disease has progressed and become more serious.

Using antibiotics on animals with viral infections

An antibiotic will not be effective against calf scours caused by rotavirus or coronavirus, or respiratory diseases caused by viruses (e.g. BVD, IBR, PI-3, BRSV). However, these conditions may be treated with antibiotics to reduce the risk of secondary bacterial infections that can result in pneumonia.

Viruses are not susceptible to antibiotics.

Monitoring the amount administered

Modern cattle feeding operations and feed mills are equipped with highly sophisticated feed processing, mixing and delivering equipment that help to ensure that each animal receives the amount of antimicrobial needed, if delivered through the feed. Injectable antibiotics are delivered even more precisely, with a specific volume given to an animal depending on its individual body weight.

Commercial and on-farm feed mills are under the regulation of the Canadian Food Inspection Agency.

Prevention of Antimicrobial Resistance

The development of antimicrobial resistant microbes can be discouraged through management practices that reduce the need for antimicrobial use, and prudent use when antimicrobials are necessary:

  • Follow label and/or veterinary instructions
  • Choose the right product to treat the condition
  • Use the proper route of delivery (oral, subcutaneous, intramuscular, or intravenous)
  • Deliver the drug in the proper dose
  • Administer the drug for the proper number of days
  • Properly dispose of expired product, empty containers and used needles
  • Follow biosecurity practices to reduce spread of infection among animals
  • Prevent stress on animals, which can weaken immune systems and increase the reliance on antimicrobials

Producers who participate in Canada’s Verified Beef ProductionTM on-farm food safety program demonstrate that they follow industry-sanctioned practices which select, use, store and dispose of antimicrobials in a responsible manner.

What if...?

Eliminating antimicrobial growth promotants, including ionophores, in cattle production would substantially reduce the overall use of antimicrobials, but would that reduce concerns about antimicrobial resistance?

Cattle drug sales in Denmark since 2001 beefresearch.caDenmark phased out the use of those products in livestock production between 1994 and 1999.  Since 2001, we can see a clear trend of increased use of prescribed veterinary antimicrobials. The decrease in antimicrobial use has happened in the “medium importance” category, antimicrobials rarely used in human medicine anymore.  Without the use of growth promoting antimicrobials, the need for antimicrobials that are important to human health increased. In addition, there has been no clear trend towards decreased antimicrobial resistance in Danish cattle or beef.

Canadian research has repeatedly shown that antimicrobials are used responsibly by Canadian beef producers, and resistance to the most important classes of antibiotics in human medicine remains extremely rare in beef cattle. Antimicrobial resistance will continue to be a research priority in Canada’s beef industry to maintain or improve current prudence. 

Continued use of antimicrobials of no importance to human health in Canadian beef production will be critical to the future competitiveness of and reduced environmental impacts by Canada’s beef sector due to improved feed efficiency and reduced animal disease.  Furthermore, the consequences of a ban on ionophores in Denmark suggest that discontinuing the use of such products would not lead to lower antimicrobial resistance, and may increase the use of antimicrobials that are important in human medicine.

Learn More

To learn more about research on this topic, see the fact sheets posted on the right side of this page.

Antimicrobial resistance: does Canadian beef production contribute?
BCRC Blog | BeefResearch.ca
http://www.beefresearch.ca/blog/antimicrobial-resistance-beef-cattle-contribution/

Latest results from antimicrobial resistance surveillance
BCRC Blog | BeefResearch.ca
http://www.beefresearch.ca/blog/antimicrobial-resistance-surveillance/

Explaining growth promotants used in feedlot cattle
BCRC Blog | BeefResearch.ca
http://www.beefresearch.ca/blog/growth-promotants/

Guidelines on "The Prudent use of Antimicrobial Drugs in Animals"
Verified Beef Production
http://www.verifiedbeef.org/downloads/responsible_antimicrobial_drug_use.pdf

Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) Annual Reports
Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS)
http://www.phac-aspc.gc.ca/cipars-picra/pubs-eng.php

Antimicrobial Resistance (AMR)
Health Canada
The use of antimicrobials in veterinary medicine are approved and regulated by Health Canada. This website explains the Government of Canada’s involvement with the issue of antimicrobial resistance related to livestock production, including Health Canada's Veterinary Drugs Directorate (VDD).
http://www.hc-sc.gc.ca

Canadian Antibiotic Resistance Alliance (CARA)
Health Canada
CARA is a research group dedicated to the study of medical microbiology/infectious diseases issues with special interest in infections caused by antimicrobial resistant pathogens as well as antimicrobial usage in Canada..
http://www.canr.info

Drug resistance
World Health Organization
http://www.who.int/drugresistance/en/

About Antimicrobial Resistance: A Brief Overview
Centers for Disease Control and Prevention
http://www.cdc.gov/drugresistance/about.html

Metaphylaxis for incoming cattle
Bovine Veterinarian
This article discusses considerations when determining if use of metaphylaxis is appropriate for a particular group of cattle.
http://www.bovinevetonline.com

Video: Antibiotics and Your Food
U.S. Farmers & Ranchers Alliance Food Dialogues
http://www.fooddialogues.com

White Paper: A One Health Approach to Antimicrobial Use & Resistance: A Dialogue for a Common Purpose
National Institute for Animal Agri culture
http://www.animalagriculture.org/Solutions/Symposia/2012_antibiotics/Antimicrobial_Use_Resistance_White_Paper_final.pdf

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Acknowledgements

Thanks to Dr. Tim McAllister, Agriculture and Agri-Food Canada Principal Research Scientist, for contributing his time and expertise to writing this page.

This topic was last revised on November 11, 2013 at 06:11 AM.

Fact Sheets

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