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 and beef are extremely low and have not increased over time. Research and surveillance evidence suggests that eliminating antimicrobial use in beef production would have clear negative health consequences for cattle with no obvious benefit for human health.


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.

Uses of antimicrobials include aquaculture, fruit production, beekeeping, livestock production, pets, wildlife, vegetation, industrial and household chemicals and human medicine. In livestock, various categories of antimicrobials are used for therapeutic (i.e. treat illness), prophylactic (i.e. control or prevent illness) and production purposes (i.e. improve feed efficiency). Canada is completely phasing out the use of antibiotics for production purposes in livestock. Other tools used for therapeutic, prophylactic and production purposes in beef production include nutrition, hygiene, vaccines, housing, anti-parasitics and enzymes.

Function of Antimicrobials

Nearly all antimicrobials are derived from those naturally produced by soil 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

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

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.

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 or category.

Categories of Antimicrobials

Antimicrobials are divided into four categories based on their importance in human medicine. Each category of importance contains antimicrobial drugs of different classes. Classes of drugs are based on their chemical makeup.

  • 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 all four categories (Low, Medium, High or Very High importance) are registered for use in beef cattle in Canada. The majority of antimicrobials that are used in Canadian beef production are of Low importance in human health (category IV), which are not used in human medicine.

Antimicrobials of Low importance include ionophores, which are used in beef cattle to prevent diseases such as coccidiosis and to improve feed efficiency.  Generally category II and III antimicrobials are used for prevention of bacterial infections in high risk groups of cattle, and treatment. Category I antimicrobials (Very High importance) are seldom used in beef cattle production and treat severe bacterial infections in overtly sick animals.

Category of Importance
in Human Medicine
Antimicrobial Class Brand Names of Antimicrobial Products
Registered for Use in Beef Cattle in Canada
I: Very High e.g. fluoroquinolones e.g. Baytil, A180
e.g. 3rd/4th generation cephalosporins e.g. Excenel, Excede
II: High e.g. macrolides e.g. Tylan, Micotil, Draxxin, Zuprevo, Zactran
III: Medium e.g. tetracyclines e.g. Liquamycin, Aureomycin
IV: Low e.g. ionophores e.g. Rumensin, Bovatec, Posistec

 

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

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 (and in veterinary 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 (and veterinarians) have no other options.

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.

Producers work with their veterinarians to develop protocols on when it's appropriate to use various antimicrobials, and adhere to withdrawal times to ensure treated animals do not enter the food system until it's safe to do so.

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. There is no evidence that ionophores 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. Multidrug resistance is similarly low, and is not increasing.

This low level of resistance is probably because drugs of Very High Importance are very rarely used in beef cattle in Canada; 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.

Click here for a summary of an ongoing Canadian study into antimicrobial use and resistance in beef cattle and the environment.

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 have 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

Viruses are not susceptible to antibiotics.

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.

Monitoring the amount administered

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

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.

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.

Avoiding Illness to Reduce the Need to Use Antimicrobials

  • Reduce stress on animals. Stress can weaken the immune system, increase the risk of disease, and increase the reliance on antimicrobials. Consider practices such as:
  • Implement vaccination programs
    • A veterinarian will help develop a feasible vaccination program, based on the level of risk in the herd, that is less costly than the expense of the disease outbreak(s) prevented
  • Ensure adequate nutrition through water and feed quality testing
  • Maintain clean, dry pens with protection from the elements
  • Use biosecurity practices to reduce spread of infection among animals
    • Minimize commingling of animals from different sources when possible
    • Isolate sick animals
    • Avoid overcrowding
  • Maintain an ongoing relationship with a veterinarian to develop and maintain a suitable herd health management program and biosecurity protocols to help prevent and contain diseases. Gather and share as much knowledge and records with your veterinarian as possible including the:
    • history of incoming cattle to help determine what is necessary for effective routine disease prevention routines with cattle on arrival
    • temperature of a sick animals
    • observed responses to treatment


Responsible Treatment When Necessary

  • Monitor cattle health on an ongoing basis to ensure prompt treatment or care.
    • Prompt treatment will usually give a better response rate and require fewer treatments. 
    • Delayed treatment can be responsible for treatment failure and then prolonged therapy as a result
    • Delayed treatment will increase the risk of spread of infection
    • Monitor effectiveness of treatment so that ineffective treatments are remedied quickly
  • Have an accurate diagnosis before using antimicrobials.
    • For example, not all lameness is footrot (a bacterial infection).
    • Viruses are not susceptible to antibiotics.
    • Antimicrobials that specifically target the pathogen should be selected over broader-spectrum agents and local therapy should be selected over systemic therapy when appropriate.
  • Choose the right product to treat the condition
    • Have a conversation with your veterinarian to help determine whether the health benefit of treatment from a particular antimicrobial drug outweighs the potential risk and burden on resistance
  • Follow veterinary and/or label instructions
    • 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
      • Treatment should not be stopped earlier than veterinary and/or label instructions indicate as reduced symptoms may be confused with a cure.
      • Provided veterinary and/or label instructions are followed, antimicrobials should be used for the shortest time period required to reliably achieve a cure. This minimizes exposure of other bacterial populations to the antimicrobial.
  • Properly dispose of expired product, empty containers and used needles
  • Know when to euthanize. It is irresponsible to give antimicrobials to an animal that has a poor prognosis rather than euthanizing. (Use acceptable procedures and equipment for euthanizing cattle as stated in the Beef Cattle Code of Practice)

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

Click to download the Canadian Veterinary Medical Association Antimicrobial Prudent Use Guidelines 2008.

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 2001there has been a clear trend of increased use of prescribed veterinary antimicrobials. There has been a drop in the use of Medium Importance antimicrobials that are rarely used in humans anymore. However, the use of High Importance antimicrobials has increased. 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 categories 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.

The Canadian beef industry strongly advocates and supports a science-based approach to the use and monitoring of antimicrobials and resistance.

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

Feedback

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Acknowledgements

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

This topic was last revised on March 23, 2015 at 02:03 AM.

Fact Sheets

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