Antimicrobial resistance is a global problem that affects to a greater or lesser degree all inhabitants of the planet. The World Health Organization (WHO) has stated that it is the most serious problem confronted by humanity. Since all antibiotic uses -- whether in human medicine or veterinary medicine -- have the potential to generate resistance, the WHO has called upon physicians and veterinarians worldwide to work jointly to solve this crisis under the “One Health” initiative1.

Likewise, the World Organization for Animal Health (OIE) published in November 2016 its strategy on antimicrobial resistance and the prudent use of antimicrobials in veterinary medicine and food-animal production2.

Definition of antibiotic stewardship

In January 2018, the American Veterinary Medical Association (AVMA) defined antibiotic stewardship as “the actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through conscientious oversight and responsible medical decision- making while safeguarding animal, public, and environmental health.” (AVMA, 2018)3.

Definition of use

As of today, the United States, the European Union (EU), Australia, Canada, Japan and many other countries have banned or restricted severely the use of medically important antimicrobials for the purpose of improving performance parameters such as weight gain and feed conversion. In general, in these countries the use of medically important antimicrobials is approved only for the prevention, control or treatment of diseases for which antibiotics are indicated.

Consequently, it is important to define each of these uses in the practice of population veterinary medicine. Recently the AVMA has approved the following definitions:

  1. Prevention/Prophylaxis: Prevention is the administration of an antimicrobial to a group of animals, none of which have evidence of disease or infection, when transmission of existing undiagnosed infections, or the introduction of pathogens, is anticipated based on history, clinical judgement or epidemiological knowledge.
  2. Control/Metaphylaxis: Control is the use of antimicrobials to reduce the incidence of infectious disease in a group of animals that already has some individuals with evidence of disease or infection.
  3. Treatment: Is the administration of an antimicrobial to those animals within the group with evidence of disease.

For treatment, the assumption is made that sick animals can be identified and segregated from the group although in the case of poultry, fish and honeybees for example, this is not feasible.

Antibiotic stewardship

Currently, programs sponsored by the WHO, OIE and local government agencies have started in many countries to ensure that medically important antibiotics are used judiciously and responsibly by the human and veterinary medical professions with the final goal of preserving their efficacy for the treatment of bacterial infections in humans and animals.

Many veterinary medical associations like the AVMA and specialty groups like the American Association of Avian Pathologists (AAAP) have produced their own guidelines and core principles for the judicious and responsible use of antibiotics in veterinary practice. In the case of poultry, the AAAP developed in collaboration with the AVMA the following core principles for the judicious and responsible use of antibiotics in poultry production4:

Commit to stewardship.

  • Engage all poultry practitioners and relevant stakeholders in the stewardship effort.
  • Develop stewardship plans to incorporate commitment and accountability for disease prevention, control and treatment while optimizing the prescribing, administration and oversight of antimicrobial drugs.
  • Identify high-priority conditions that are commonly treated with antimicrobial drugs on which to focus stewardship efforts.
  • Demonstrate commitment to systemically assessing the outcomes of antimicrobial drug therapy.
  • Within your organization, form a committee with oversight on antimicrobial stewardship and judicious use.

Commit to the judicious management, use and administration of antimicrobial drugs.

Advocate for a system of care to prevent, treat and control poultry diseases.

  • Promote improvements in the areas of farm management, biosecurity and vaccination strategies.
  • Work with farmers, allied partners and stakeholders to adopt preventive and management strategies to minimize the need for antimicrobial drugs. These strategies include animal husbandry and hygiene, biosecurity and infection control, nutrition and vaccination programs.
  • Provide alternative strategies to antimicrobial drugs in the prevention, control and treatment of poultry diseases to optimize outcomes in health, welfare and food safety.

Select and use antimicrobial drugs judiciously. 

  • Use an evidence-based approach for making a diagnosis and determining whether an antimicrobial drug is indicated.
  • Make an informed selection of an antimicrobial therapy using laboratory diagnostics such as culture and sensitivity of pathogens.
  • Follow FDA Guidance for Industry # 209 and 213 and the modernization of the VFD process that outlines directions for water soluble and feed additive administration of antimicrobials in food-producing animals.
  • Refer to the use of “Guidelines for Judicious Therapeutic Use of Antimicrobials in Food-producing Animals” like the ones produced by the AVMA and the AAAP5,6
  • Continually assess outcomes of antimicrobial therapy.

Evaluate antimicrobial drug use practices.

  • The prescription of antimicrobial drugs by the poultry veterinarian must be continuously evaluated.
  • Encourage the analysis and sharing of data on antimicrobial drug use to encourage collaboration between poultry producers, researchers and government agencies to verify actual practices and stimulate innovation in this field.

Educate and build expertise

  • Make resources available and encourage the development of expertise in antimicrobial stewardship.
  • Provide continuing education opportunities for poultry veterinarians related to antimicrobial use and alternatives.
  • Continue to educate our partners and stakeholders on management, biosecurity and production practices to ensure poultry health, welfare and food safety.
  • Continue to evaluate judicious use and stewardship guidelines in the light of new practices and innovations.
  • Support research on antimicrobial drug use and resistance. Advocate for the development and approvals for antimicrobial and alternative therapies not used in human medicine.

Classification of antimicrobials according to their medical importance 

In the USA the Food and Drug Administration (FDA) has ranked antimicrobial drugs used in veterinary medicine in the following categories7:

  1. Critically important (Ex. 3rd generation cephalosporins, fluoroquinolones, macrolides, potentiated sulfonamides).

  2. Highly important (Ex. Natural penicillins, aminopenicillins, aminoglycosides, lincosamides, glycopeptides, streptogramins, tetracyclines, sulfonamides).

  3. Important (Ex. 1st and 2nd generation cephalosporins, cephamycins, monobactams, quinolones).

  4. Not important (Ex. Bambermicins, ionophores, cyclic polypeptides).

Based on this classification is that many poultry companies in the U.S. and other countries have voluntarily ended the practice of injecting hatching eggs “in-ovo” at transfer time with gentamicin (an aminoglycoside) and in the case of ceftiofur (a 3rd generation cephalosporin) the FDA ban on extra-labeldrug use eliminated its use “in-ovo”.

Important differences

The meaning of the labels for poultry raised without antibiotics (in the U.S.: ABF (antibiotic-free); RWA (raised without antibiotics) or NAE (no antibiotics ever) varies among different countries and organizations around the world. For example, in the U.S., ionophore anticoccidials are classed as antibiotics and therefore cannot be used in poultry that claim to have been raised without antibiotics while in the EU ionophore anticoccidials are not considered antibiotics and therefore can be used in poultry and maintain the claim to have been raised without antibiotics.

Unlike the U.S., in the EU, due to animal welfare concerns, flocks raised without antibiotics are permitted to be treated with them when an outbreak of bacterial disease occurs and retain their status.

Final comments 

The use of medically important antibiotics in food-producing animals will be more scrutinized each day to verify that they are only used to prevent, control or treat diseases that will respond favorably to antibiotic therapy and under strict veterinary supervision.

The WHO has launched worldwide programs to compile data on antimicrobial resistance in pathogens and commensals isolated from both, humans and food-producing animals7; one of the objectives is to correlate antibiotic use with the development of antimicrobial resistance and its possible transmission to humans. All countries of the world have been called upon to participate and do their part. Another objective of the WHO stewardship programs is to end the practice of selling medically importantantibiotics without a prescription in both, human and veterinary medicine, under the “One Health” plan1.

In the U.S. as of 1 January 2017, all antibiotics deemed medically important and administered by the oral route can only be used by prescription by a licensed veterinarian if administered by the drinking water or by the submission of a VFD (Veterinary Feed Directive) order by a licensed veterinarian if administered via the feed. Canada is implementing similar requirements starting December 1, 2018.

The responsible handling and judicious use of antibiotics by food-animal veterinarians will become more critical and will require that veterinarians adhere to good principles of administration and responsible use.

References

  1. World Health Organization, 2018. Tackling Antimicrobial Resistance (AMR) Together. Working

    paper 1.0: Multisectoral coordination. Geneva, Switzerland.

  2. OIE, 2016. The OIE Strategy on Antimicrobial Resistance and the Prudent Use of Antimicrobials.

  3. American Veterinary Medical Association, January, 2018. Antimicrobial Stewardship Definition and

    Core Principles. https://www.avma.org/News/JAVMANews/Pages/180301d.aspx

  4. AAAP, Antimicrobial Stewardship for Poultry.

    https://www.aaap.info/assets/Positions/AAAP%20Antimicrobial%20Stewardship.pdf

  5. AVMA. Antimicrobials: Guidelines for Judicious Therapeutic Use.https://www.avma.org/KB/Resources/Reference/Pages/Antimicrobial-use.aspx

  6. AAAP-AVMA. Guidelines for Judicious Use of Therapeutic Antimicrobials in Poultryhttps://www.avma.org/KB/Policies/Pages/AAAP-Guidelines-to-Judicious-Therapeutic-Use-of- Antimicrobials-in-Poultry.aspx

  7. Guidance for Industry # 152. Evaluating the safety of antimicrobial new animal drugs with regard to their microbiological effects on bacteria of human health concern. U.S. Department of Health and Human Services, Food and Drug Administration Center for Veterinary Medicine. October, 2003.

  8. World Health Organization, 2018. Monitoring global progress on addressing antimicrobial resistance. Analysis report of the second round of results of AMR country self-assessment survey.