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Antimicrobial fact sheet for veterinarians

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The judicious use of antimicrobials in food animals keeps them healthy, and healthy animals mean healthy food products for humans. Judicious use means that veterinarians and producers use good judgment to decide when and how an antimicrobial is to be used to maximize public and animal health benefits while minimizing risks.1,2

  • Antimicrobials and other medications given to food animals have specific FDA-regulated withdrawal times to ensure that no harmful drug residues are present in milk or meat. Withdrawal times indicate the time required after administration of a drug to a food-producing animal to assure that drug residues in milk or meat are below the residue limit determined by the FDA.
  • Animal food products found at the grocery store are from animals that are harvested only after FDA-regulated withdrawal times have been observed (if a drug was administered to the animals). When withdrawal times are observed, no antimicrobial residues that can cause harm to people who consume them should be present in milk or meat products.

It is crucial that safe and effective antimicrobials remain available for use in veterinary medicine to ensure the health and welfare of animals, and consequently the health of humans. The Preservation of Antibiotics for Medical Treatment Act (PAMTA) is a bill that seeks to eliminate many of the beneficial uses of antimicrobials, but the rationale for its enactment is not supported by scientific data.

  • Bans or restrictions such as those proposed in PAMTA are likely to negatively affect animal health and potentially negatively impact food safety. Specifically, PAMTA would prohibit veterinarians from implementing disease prevention and possibly disease control measures using antimicrobials. Only therapeutic antimicrobial administration would be allowed. Clearly, this could result in greater numbers of clinically and subclinically infected animals. As a result of increased handling and difficulty in processing, subclinically infected food animals pose an increased risk of carcass contamination with enteric pathogens.3,4
  • Delaying antimicrobial therapy until clinical signs are evident throughout the herd or flock can increase the potential for the development and spread of resistant pathogens. Clinical infections require treatment with higher doses (and therefore increased quantities) of antimicrobials and the drugs used for treatment are more often in the same classes as highly important human antimicrobials.

Multiple governmental organizations including the USDA and FDA, as well as veterinarians in practice, strive to ensure that America's food supply is safe. Animals, and thus our food supply, are kept healthy with judicious use of antimicrobials, vaccinations, parasiticides, good nutrition and good management practices.

  • Veterinarians are committed to protecting and preserving animal welfare, which includes all aspects of the animal's well-being: proper housing, management, nutrition, disease prevention and treatment, responsible care, humane handling, and, when necessary, humane euthanasia.5

The U.S. Food and Drug Administration has approved the use of antimicrobials for four purposes: growth promotion/feed efficiency, prevention of disease, control of disease, and treatment of disease.1

  • Although some groups have estimated antimicrobials used for growth promotion to be as high as 70%, others have estimated the use to be much lower (5-30%) depending upon the year and types of antimicrobials included in the estimate.6,7

Several types of antimicrobials are used for production or enhancing growth, to alter the animal's gut microflora, and to decrease the level of pathologic bacteria present. These are often referred to as growth promoters. Antimicrobials should not be confused with growth hormones or performance-enhancing drugs, such as steroids.

  • Some groups believe that antimicrobials should only be used when an animal shows obvious clinical signs of disease.
  • Antimicrobials for production enhancement purposes are administered at low doses in the feed. Some groups are concerned that feeding antimicrobials at low levels over time could enhance bacterial abilities to develop resistance, Other groups believe high-level uses are potentially stronger drivers for the development of resistance.
  • The Netherlands and Denmark have instituted bans on the use of antimicrobial growth promoters and neither ban resulted in a significant decrease of antimicrobial resistance in humans. There is evidence that animal morbidity and mortality initially increased following the bans, yet recent information indicates that morbidity and mortality rates have stabilized to levels present before the ban. However, the therapeutic use of antimicrobials, at higher doses and often involving antimicrobials used more widely in human medicine, continues to increase.8,9,10 Reports from the Netherlands indicate a 100% increase in therapeutic uses that is attributed to the ban on growth promotants. 10

Animal illness can be predictable and occur with some regularity even in well-managed conditions, thereby requiring interventions (including antimicrobial therapy) as a preventive course of action. Veterinarians have the education, skills, and expertise to be able to predict the regularities in which these disease conditions occur and be able to prevent them when the tools (including antimicrobials) are available.

  • Strategic use for disease prevention (where predictable disease exposures occur but where the exposure may not yet have been documented) and control (where disease is present in a portion of the herd or flock and will likely spread) is essential for animal health and welfare.
  • FDA believes that some prevention indications are necessary and judicious.
  • Studies show that reductions in animal disease can reduce bacterial contamination on meat, thereby improving food safety and potentially reducing human foodborne illness.3,4

There are only a limited number of antimicrobials for human and animal use. Therefore, veterinarians are just as concerned about resistance as human health professionals.

  • Although some drugs (e.g., ionophores, arsenicals) used in food animals are technically antimicrobials, they have no relevance to human resistance trends.
  • The vast majority of antimicrobials available are used in both human and veterinary medicine. To restrict the uses of drugs important to human medicine would severely limit drugs available to veterinarians and therefore compromise animal health.
  • On a per capita basis, human and companion animal antimicrobial use is 10 times greater than that of food producing animals.12

Although over-the-counter (OTC) antimicrobials are available, they are well regulated. In fact, there are greater restrictions on the use of antimicrobials in animals than there are for use in humans.

  • Individuals using OTC products who deviate from the label instructions in any manner are also committing an illegal act, unless there is veterinary supervision AND compliance with extralabel drug use (ELDU) regulations.
  • All FDA-approved drug products for feeding to animals are restricted to a very specific use, dose, and duration and can be used ONLY as indicated on the label.
  • Both FDA and AVMA agree that veterinarians should be involved in the decision-making process for the use of antimicrobials regardless of the distribution channel through which the antimicrobial was obtained13, and therefore it is unlikely that any further antimicrobials with OTC status will be approved.

All uses of drugs in food-producing animals is subject to federal regulation

  • Any use that deviates from the label is illegal unless under the supervision of a veterinarian and in accordance with ELDU regulations.
  • Veterinarians (and under veterinary supervision, producers) are strictly prohibited from using certain drugs extralabelly (including specific antimicrobials) in food animals because the FDA has determined there is a public health risk with treating animals with these drugs in an extralabel fashion.

Veterinary Feed Directive (VFD) is a category of drugs intended for use only in or on animal feed, must be used exactly as prescribed, and require the direct supervision of the veterinarian as well as a valid veterinarian-client-patient-relationship. The extralabel use of a VFD drug is not permitted under any circumstances because the drug goes into animal feed.

  • Some suggest that OTC antimicrobials should not be available without prescription or VFD to ensure that animals being treated with antimicrobials are being treated only under a veterinarian's direction and to facilitate judicious use. However, changing a drug's approval category from OTC to prescription or VFD is complex and would require numerous changes to the FDA's processes; currently, the FDA has no mechanism for changing approval categories. Moreover, extensive coordination and communication between the FDA, producers, and veterinarians would be necessary to ensure wide understanding of any revised FDA rules.

There are 3 theorized mechanisms for the spread of resistance from food animals to humans predicated on the assumption that antimicrobial use in food animals affects human resistance through the consumption of animal products:

  • Directly – when a human consumes resistant bacterium in a food product;
  • Indirectly – when a person acquires a resistance determinant (such as a plasmid) from the food source and an effective gene transfer occurs, which results in the person acquiring a resistant infection;
  • Via residues – when residues remain at a level that can impact the development of resistance. This risk only exists if there are a series of flaws in the system that has been designed to protect the public from potentially harmful drug residues in food products.
  • All of these mechanisms need to be further researched to determine their significance in the overall issue of antimicrobial resistance.14

Antimicrobial resistance is most commonly seen when a pathogen is transmitted from human to human. Several cases have been reported that show direct transmission of a resistant organism from animal to human; however, Based on peer-reviewed risk assessment to date, the risk to people of becoming infected with resistant organisms by consuming animal products (meat, milk, eggs) is extremely low.15,16,17,18,19,20,21,22,23 The indirect foodborne route of transmission has never been demonstrated.

  • Bacterial foodborne infections are rarely resistant. Furthermore antimicrobial treatment for foodborne infections is often contraindicated. For example, antimicrobial therapy for non-typhi Salmonella is generally not indicated because it has no effect on clinical illness and prolongs carriage and excretion of the organism. Treatment of enterohemorrhagic E. coli (E. Coli O157) may increase the risk of developing hemolytic uremic syndrome.24
  • Antimicrobial resistant strains can have more, less, or the same level of virulence when compared to the antimicrobial-sensitive form of the same strain.25

Based on available science, the likelihood that human consumption of animal products (meat, eggs, milk) will lead to an infection with resistant organisms is negligible.1

  • There are multiple mechanisms in place to ensure the safety of animal products, such as inspections to continually test animal products for bacterial contamination and drug residues throughout their production. Some confusion regarding residues stems from labels indicating that a product is "antibiotic free" or "hormone free." This can be misleading because all food products are required by FDA and USDA to be free from unsafe antimicrobial and hormone residues.
  • Primary risk factors for foodborne illness include improper handling, preparation and cooking of animal products. It is still critical to properly handle and cook all animal products before consumption to minimize the human health risks including those associated with potential resistance. Routine good food hygiene is essential for the prevention of bacterial foodborne resistant bacterial infections.

Each drug must be considered individually because of relative risks, benefits, and differing abilities to select for resistance. The benefits of some uses for animal health and welfare may outweigh the risks.

  • Increased doses and stronger drugs are used for treatment versus prevention and control. Therefore, delaying antimicrobial therapy until clinical signs are evident could mean that more animals will need treatment, which could, in turn, increase the potential for the development and spread of resistance.
  • Prevention and control of disease can minimize animal suffering associated with disease conditions.
  • Although bacteria can transfer genetic material that encode for resistance, the recipient may not have the appropriate mechanisms for expressing the resistance gene and therefore does not automatically become resistant. For example, methicillin resistant Staphylococcus aureus (MRSA) is defined by the presence of the mecA gene. However, MRSA is sensitive to methicillin in the absence of the fem gene activation.

More research and risk-based analyses are needed to determine the risks associated with antimicrobial use and to formulate a strategy to maximize the benefits while minimizing the risks before we institute stringent legislation that could negatively affect not only the health of animals, but also human health.

  • The development and transmission of resistance is extremely complex, and many of the details of how and why these events occur remain unclear.
  • Risk analysis includes risk assessment, risk communication, and risk management actions that are commensurate with the level of risk determined through risk assessment. Risk analysis should continue to evaluate the risks and benefits to animal health and welfare in addition to the risks and benefits to human health attributed to uses in animals.26
  • Some antimicrobial uses in animals pose a risk to human health, yet it is most important to consider the level of risk. Risk assessments on antimicrobial resistance in animals thus far have shown very low risk to human health. However, to say there should be zero risk would be unrealistic, even with bans on antimicrobial use.

The AVMA would like to thank Dr. Scott Hurd, Professor, Iowa State University College of Veterinary Medicine and member of AVMA Council on Biologic and Therapeutic Agents (COBTA) representing epidemiology; and Jessica Green, University of Illinois College of Veterinary Medicine Class of 2012; for their contributions to this document.

REFERENCES
1. Frequently Asked Questions about Antimicrobial Use and Antimicrobial Resistance, AVMA (Available at http://www.avma.org/public_health/antimicrobial_use.asp)
2. Judicious Therapeutic Use of Antimicrobials (Available at http://www.avma.org/issues/policy/jtua.asp)
3. Hurd, H.S., Brudvig, J., Dickson, J., Mirceta, J., Polovinski, M., Matthews. J., Griffith. R. 2008. Swine health impact on carcass contamination and human foodborne risk. Public Health Reports. 143 pp 343:351.
4. Singer, R.S., Cox, L.A., Dickson, J.S., Hurd, H.S., Phillips, I., Miller, G.Y. 2007. A model of the relationship between food animal health and human foodborne illness. Prev Vet Med. 79 pp 186-203.
5. Animal Welfare Overview. (Available at http://www.avma.org/issues/animal_welfare/default.asp)
6. Preservation of Antibiotics for Medical Treatment Act http://thomas.loc.gov/cgi-bin/bdquery/z?d111:H.R.1549:
7. [AHI] Animal Health Institute. 2005. Antibiotic use in animals rises in 2004. News release. Washington, D.C.: AHI.
8. Political Bans on Antibiotics are Counterproductive,European Test Case: Increased Animal Disease, Mixed Human Health Benefit. (Available at http://www.ahi.org/files/Antibiotics%20in%20Livestock/H.%20Danish%20experience.pdf )
9. DANMAP 2008. Use of antimicrobial agents and occurence of antimicrobial resistance in bacteria from food animals, foods and humans in Denmark. ISSN 1600-2032. (Available at www.danmap.org)
10. MARAN 2008. Monitoring of antimicrobial resistance and antibiotic usage in animals in the Netherlands in 2008. (Available at: www.cvi.wur.nl.)
11. FDA Draft Guidance #209 The Judicious Use of Medically Important Antimicrobial Drugs in Food-Producing Animals. U.S Department of Health and Human Services, Food and Drug Administration, Center for Veterinary Medicine. June 28, 2010.
12. Barber DA. New perspectives on transmission of foodborne pathogens and antimicrobial resistance. J Am Vet Med Assoc 2001;218:1559-1561.
13. Discussions of the Antimicrobial Use Task Force. (Available at www.avma.org/AUTFreport)
14. Hoang, C. "It has been proven... or Has it?" International Conference on the Use of Antimicrobials in Cattle Production. May 2009.
15. Swartz, Morton. Report of a Study; Human Health Risks with the Subtherapeutic Use of Penicillin or Tetracyclines in animal feed. Washington, DC: Institute of Medicine, 1988.
16. FDA Center for Veterinary Medicine. The human health impact of fluoroquinolone resistant campylobacter attributed to the consumption of chicken. Silver Spring, MD: FDA Center for Veterinary Medicine, 2001. Available at: www.fda.gov/downloads/AnimalVeterinary/SafetyHealth/RecallsWithdrawals/UCM042038.pdf. Accessed Jul 7, 2010.
17. Hurd S. et al. Public Health Consequences of Macrolide Use in Food Animals: A Deterministic Risk Assessment. J Food Protection 2004; 67:980-992.
18. Cox LA. et al. Human Health Risk Assessment of Penicillin/Aminopenicillin Resistance in Enterococci Due to Penicillin Use in Food Animals. 2008. In Press.
19. Alban, L. et al. A human health risk assessment for macrolide-resistant Campylobacter associated with the use of macrolides in Danish pig production. Prev Vet Med 2008; 83:115-129.
20. Cox LA. Potential human health benefits of antibiotics used in food animals: a case study of virginiamycin. Environ Int 2005; 31:549-63.
21. Cox LA, Popken DA. Quantifying Potential Human Health Impacts of Animal Antibiotic Use: Enrofloxacin and Macrolides in Chickens. Risk Analysis 2006; 26:135-146.
22. Phillips I. et al. Does the use of antibiotics in food animals pose a risk to human health? A critical review of published data. J of Antimicrobial Chemotherapy 2004: Vol 53, pp 28-52.
23. Cox LA. et al. Quantifying Human Health Risks from Animal Antimicrobials. Interfaces. 2007; 37:22-38.
24. M. Bennish and W. Khan. Therapy Guidelines for Enteric Infections – A 12-Year Update. 2007. In APUA Newsletter, Vol. 25, No. 3, pp. 1-4.
25. Holmberg, S.D. J.G. Well, and M.L. Cohen, "animal to Man Transmission of Antimicrobial Resistant Salmonella: Investigations of U.S. Outbreaks, 1971-1983,"Science,225:833-835,1984
26. Antimicrobials in Livestock Feeds. (Available at http://www.avma.org/issues/policy/jtua_feeds.asp)

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