The Debate Over Antibiotic Use in Animal Agriculture
In the News
September 23, 2012
Earlier this year, a federal judge ordered the FDA to reconsider two petitions seeking restrictions on the use of antibiotics in animal agriculture. The order comes amidst longstanding concerns about usage trends for antibiotics in animal agriculture and how those trends relate to antimicrobial resistance in both animals and humans. While antibiotic use in humans is closely monitored by our nation’s health care system, there is no equivalent monitoring for animals.
The FDA announced back in 1977 that they would begin banning some agricultural uses of antibiotics but eventually retreated. Now, the organization is calling on livestock producers to voluntarily reduce the use of antibiotics in their herds – even as producers say that antibiotics are necessary for ensuring animal health. Almost 29 million pounds of antibiotics are sold for use in food animals in the United States, according to the FDA.
To learn more, we talked to Dr. Meghan F. Davis, Postdoctoral Fellow with the Department of Environmental Health Sciences at Johns Hopkins Bloomberg School of Public Health, and Dr. Randall Singer, Associate Professor of Epidemiology at The University of Minnesota, about what this debate means for both animal producers, veterinarians and consumers.
How are antibiotics used in animal agriculture?
Davis: Antimicrobial drugs, which include antibiotics designed to kill or inhibit the growth of bacteria, may be used in variety of ways in animal agriculture. Some drugs are used to treat sick animals. I support this use when it is under the direction of a veterinarian who has diagnosed the disease condition. Similarly, when a veterinarian has been on a farm treating ongoing, chronic disease conditions in a herd or flock, sometimes that veterinarian will need to treat the entire group of animals to manage the disease condition. Typically, the veterinarian will also diagnose and address underlying factors on the farm that may foster the disease outbreak, spread, or persistence. This kind of ongoing relationship between a veterinarian, a farmer, and the animals on the farm is critical to good antimicrobial drug stewardship.
Some food animal producers feed antimicrobial drugs for economic gain (for example, to make animals grow faster), and they may do so without the oversight of a veterinarian. Many antibiotics are available to farmers over-the-counter (without a veterinarian prescription). In a recent survey by the United States Department of Agriculture, dairy producers reported giving antimicrobial drugs over 50% of the time without consulting a veterinarian.1 This may result in unnecessary – and potentially risky – use of antimicrobial drugs.
Singer: Antibiotics are used in animal agriculture in four FDA-approved ways: disease treatment, disease control, disease prevention, and feed efficiency (growth promotion). Briefly, disease treatment refers to the use of the antibiotic in an ill animal. Disease control refers to the use of the antibiotic in a population of animals during a time of diagnosed illness. Not all of the animals receiving the antibiotic are necessarily ill at the time of antibiotic administration. Disease prevention refers to the use of the antibiotic in an animal or in a population of animals at a time when it is known that the animals are susceptible to disease and a disease risk is present. Finally, growth promotion refers to the use of the antibiotic in a low-dose fashion to improve the weight gain and feed efficiency of the animal. This type of use has been termed “production use” in recent FDA documents.
All four of these use categories result in an improved health of the animal receiving the antibiotic, and to reiterate, all four of these use categories have been approved by the U.S. FDA, although not all categories are approved for all antibiotics. While some might say that growth promotion antibiotics are used only for the economic gain of the producer, this statement is completely misleading and unfair, as animals receiving antibiotics for growth promotion are healthier. Producers putting healthier animals into the food supply should be rewarded with higher economic returns. With that said, producers, veterinarians, and agricultural scientists are constantly looking for strategies to maintain this high level of animal health in the absence of antibiotics.
One area of confusion regarding the ways in which antibiotics are given to animals is related to the administration in the feed of the animal. Uses of antibiotics that are “in-feed” are often equated with growth promotion and are assumed to be long-term low-dose regimens of antibiotic administration for the sole purpose of improving animal weight gain. In fact, all four of these antibiotic use categories can be applied via the feed or the water because the only realistic way to administer an antibiotic to populations of animals, such as a flock of chickens, is through the feed or the water. When a flock of chickens is sick, the only way to treat the disease and control its spread is to administer the antibiotic to the entire flock via the feed or the water. In many instances, antibiotics used for disease treatment and disease control will be given via the drinking water because sick animals may stop eating but often continue to consume water.
Finally, the importance of antibiotics for disease prevention should not be underestimated; it should always be preferable to prevent disease than to treat a whole flock or herd of diseased and soon-to-be-diseased animals once an outbreak has begun. In fact, one of the central tenets of medicine is to minimize negative health impacts by maintaining a healthy population in the first place.
What are the benefits of using antibiotics in animal agriculture? What are the risks?
Singer: The main benefit of using antibiotics in animal agriculture is the fact that antibiotics help keep animals healthy. Just as in human medicine, antibiotics used in veterinary medicine can cure disease, diminish the severity of disease, and keep animals healthy at times when they are at risk of getting sick. All four categories of antibiotic use described in the previous section provide the benefit of keeping animals healthy. As will be discussed in a later section, keeping animals healthy also leads to a healthier food supply and therefore healthier people.
The main risk of using antibiotics in animal agriculture is the propagation of antibiotic resistant bacteria. These bacteria can be resistant to antibiotics that are critically important in human medicine. If people get sick with bacteria that are resistant to important antibiotics, they might experience more severe symptoms for longer periods of time. In rare instances, the inability to treat an antibiotic resistant infection in people can lead to severe disease and even death. Everyone involved with animal agriculture has the same ultimate interest: keeping animals healthy and placing healthy animals into the food chain. We are also well-aware of the negative health impacts that antibiotic resistant bacteria can have on human and animal health. Concerns over antibiotic resistance are not new, and consequently, people working in animal agriculture, from the producer to the veterinarian to the animal scientist, have always been looking for comprehensive management strategies for maintaining animal health; antibiotics are only one component to this comprehensive strategy.
Davis: Antibiotics used in any setting (human or animal) may select for bacteria that are resistant to the drugs. If just a few bacteria are resistant to an antibiotic, compared to millions that are susceptible, when you administer the antibiotic, then the susceptible bacteria will die and the resistant bacteria will multiply. This can occur in both pathogens (“bad”) and commensal (“good”) bacteria. Further, bacteria share genes for antimicrobial resistance between them, meaning that a resistant bacterium can enable a susceptible bacterium to become resistant. In some cases, bacteria can obtain multiple genes for resistance to different antimicrobials all at once; hence, using just a single antibiotic might drive selection for resistance to multiple types of antibiotics. An example of an often multidrug-resistant bacterium is methicillin-resistant Staphylococcus aureus (MRSA).
In all settings, doctors and veterinarians have to balance the risks of promoting resistant bacteria with the benefits of treating disease in humans and animals. Limiting uses of antibiotics to those required for disease treatment when disease has been diagnosed by a veterinarian is an appropriate step toward protecting drugs for treatment of disease in both humans and animals.
How do improvements in animal health relate to human health?
Davis: Sick food animals should be treated, not just for good animal health, but also to protect the food chain. Just as with humans, preventative control of disease through good living conditions, vaccination, and disease surveillance is important to maintain healthy food animals. Antibiotics should be used only when medically necessary.
Using antibiotics prophylactically may not always be best for animal health. For example, in one research study, groups of dairy cows were either given antibiotics whenever they had any signs of diarrhea, or were given antibiotics only when they had a fever (the veterinarian recommended treatment).2 The veterinarian-directed treatment was cheaper and actually led to fewer days of diarrhea. Continued diarrhea in animals on antibiotics may be due to the unintended effects of antibiotics to kill off the normal intestinal bacterial flora, which can disrupt gastrointestinal health. When this happens in people who are taking antibiotics, similar effects, such as diarrhea and vomiting, can occur.
Singer: The health of animals, humans and the environment are intricately related. Healthy animals being raised for food tend to have lower levels of harmful bacteria, such as Salmonella and Campylobacter, than animals that have experienced illness during their lives. Furthermore, meat produced from animals that have been healthy their entire lives can have lower levels of potentially harmful bacteria, thereby leading to a reduced risk of foodborne illness in people. Consequently, actions that maintain the health of animal populations can have the effect of improving human health through reduced risk of foodborne illness. These actions can include the judicious use of antibiotics, vaccination programs, and sound management practices. A very recent report by the Council for Agricultural Science and Technology (CAST) entitled “The Direct Relationship between Animal Health and Food Safety Outcomes” addresses this issue in detail.
Does the use of antibiotics in animal agriculture lead to drug resistance?
Singer: ALL uses of antibiotics can lead to antibiotic resistance to some degree in specific bacteria. This includes antibiotics used in human medicine, veterinary medicine and animal agriculture, and crop-based agriculture. When people state that certain approved antibiotic uses are “abuses” or “misuses” they are making an overly simplistic assessment of the situation. The important question that we should be asking is how to ensure that public health and environmental health are maximized while maintaining animal health.
To address this type of holistic question, we must recognize that antibiotics used for disease treatment in animal agriculture are often the same antibiotics that are critically important in human medicine. When animals get sick, these critically important antibiotics are often the only antibiotics that work against bacterial diseases. However, the antibiotics that are used for growth promotion and disease prevention are often older antibiotics that are not considered critically important to human medicine. If these antibiotics are used appropriately, animal disease can be prevented or minimized, thereby eliminating the need for critically important antibiotics to treat the sick animals.
Davis: Any use of antibiotics (old or new) in any setting can lead to selection for drug resistance, but the majority of the 29 million pounds of antimicrobial drugs sold or distributed for use in food animals are administered in medicated feed or water, a practice that may increase selective pressure for resistant bacteria.3
Recent detective work by scientists studying MRSA in pigs and other livestock demonstrated that agricultural practices may promote selection of antimicrobial resistance in bacterial strains that can infect humans.4 By studying the genetic code of one particular S. aureus strain, they found that a susceptible S. aureus (a MSSA, or methicillin-susceptible S. aureus) initially came from humans before it entered the livestock population. As the strain colonized farm animals, it acquired genes for resistance to tetracyclines and for resistance to a group of antibiotics that include methicillin, penicillin, and cephalosporins. In other words, the MSSA became a MRSA strain after it colonized livestock. This MRSA strain, termed CC398, has been able to infect livestock workers, their family members, and sometimes people in the general community. The scientists who studied this strain were concerned that the feeding of tetracycline drugs to livestock may have promoted its spread, since CC398 often is resistant to both tetracycline drugs and methicillin.
Singer: It is easy to cite individual studies that seem to support one’s ideas or agendas. The topic of MRSA in animal agriculture is often used to demonstrate that antibiotics in animal agriculture can lead to an antibiotic-resistant bacteria that can cause human disease. Unfortunately, a thorough reading of the literature will be frustrating for these individuals because there are no studies that will demonstrate an antibiotic used in animal agriculture that has led to the emergence of the MRSA strains associated with animal agriculture. In fact, the MRSA strains associated with animal agriculture emerged AFTER all growth promoting antibiotics were banned in Europe. After the ban, producers began to use other compounds with antimicrobial properties, such as zinc oxide, to treat, control and prevent the high incidence of animal diarrhea they observed after antibiotics were banned. The MRSA strains from animals are actually resistant to zinc while the susceptible strains are not, a fact only mentioned briefly in the paper by Price et al. It appears that it is the use of zinc that has resulted in the emergence of the MRSA strains in animals. Banning the growth promoting antibiotics because of a perceived negative impact on human health resulted in many more sick animals, thus requiring alternative therapies; the use of zinc and other compounds increased. This unfortunate story represents a classic case of an unintended consequence from making policy decisions in the absence of science.
What is the best way to manage antibiotics use in animal agriculture? How do you think they will be used in the future?
Singer: Antibiotics are an integral component of animal health. All uses of antibiotics improve animal health, even if a few individual studies selectively pulled from the literature seem to show no net health improvement in a specific situation on a particular set of farms. These improvements in animal health can substantially improve human health. The “production“ uses of antibiotics, which have the unfortunate, decades-old label claim of improving feed efficiency and average daily weight gain, have the clear and documented effect of improving animal health. All uses of antibiotics may also pose a risk, mainly associated with increases in antibiotic resistance. The best way of managing antibiotic use in animal agriculture is to maximize the benefits and minimize the risks associated with the agricultural use of antibiotics. Simply removing antibiotics from use in animal agriculture may help reduce some of the antibiotic resistance circulating today, but it might also have severe unintended consequences including negative impacts on human health. The best way to manage antibiotic uses in animal agriculture is through sound, rational, science-based policy. Only a handful of peer-reviewed quantitative risk assessments have been conducted on the impacts to human health associated with the use of antibiotics in animal agriculture; this approach needs to be utilized more broadly for deciding on the optimal means for managing antibiotics in animal agriculture. A successful management strategy is one that will optimize human, animal and environmental health, and quantitative risk assessments can identify those strategies. Opinions such as “disease prevention antibiotic uses are bad while disease treatment antibiotic uses are good” should be formally tested in these risk assessment models. The reason why the U.S. has not restricted more antibiotics in animal agriculture is because the risk assessments that have been conducted have shown a negligible risk to human health associated with the antibiotics being evaluated.
In the future, antibiotics should and hopefully will continue to be a key component of the veterinarian’s toolbox for maintaining healthy animal populations. The ways in which antibiotics are used will hopefully be based on a thorough, rigorous assessment of the risks and benefits of each use and not on opinion-based perceptions. For example, although antibiotics given for growth promotion or disease prevention might be unpopular in public opinion polls, a scientific assessment of these uses would demonstrate that they reduce the amount of critically important antibiotics being used in animals and help reduce disease in animal populations. Future assessments of antibiotic uses should be taking a holistic view of the benefits and risks associated with antibiotics, including the unintended consequences of making changes to antibiotic use practices, and should aim toward the design of strategies that result in the greatest net benefit to human, animal and environmental health.
Davis: Not all uses of antibiotics improve animal health, as veterinary research studies demonstrate,5 and some uses drive antimicrobial resistance in human pathogens. The FDA conducted a risk assessment of fluoroquinolone antibiotic use in poultry, linking it to a rise in fluoroquinolone resistance in the human foodborne pathogen Campylobacter. As a result, the FDA banned fluoroquinolone use in poultry in 2005.
Currently under debate are what categories of antimicrobial use the FDA should continue to support. My recommendation is that antibiotic use in food animals should be the same as it is for all other settings: by prescription and in the context of a veterinarian-patient-client relationship. A veterinarian who makes routine farm visits not only can diagnose disease, conduct appropriate testing (such as collection of specimens for bacterial culture and antimicrobial sensitivity analysis) and prescribe appropriate treatment, but also can make recommendations for management practices to help prevent disease spread and address any unintended consequences of antimicrobial use. Growth promotion and other non-therapeutic uses (production uses) should be restricted, antibiotics should be given for short, therapeutic durations instead of chronic use, and where possible, antibiotics should be administered to food animals by injection instead of in medicated feed. Where antibiotics must be administered via feed or water, sick animals should be separated from the flock or school to allow more targeted treatment and supervision to be sure the animals actually consume the medication.
Antibiotic drug use (for humans or animals) should be the same in all settings. Sound scientific (peer-reviewed) evidence identifies rational concerns with the current widespread uses of antimicrobial drugs in animal agriculture.6 A larger effort needed to preserve antibiotics to promote human and animal health requires legitimate restrictions on production uses in animal agriculture. Numerous studies in the peer-reviewed literature do not support continued production uses as a means of addressing the growing crisis of antimicrobial resistance in both humans and animals. The most simple and fair approach to the public, to farmers, and to healthcare providers of all types is to make use of antimicrobials equal in all settings: by prescription to treat disease. Restricting production uses of antibiotics is far from an “individual agenda.” Federal agencies originally considered restrictions in the 1970s, and industry has continued to oppose such measures through legal channels.6 Such restrictions are critical to combat the growing problem of antimicrobial resistance while providing the ability for veterinarians to act as appropriate stewards, working with their farmer clients to safeguard animal and human health.
The opinions expressed herein are from Dr. Davis and Dr. Singer and do not necessarily reflect the views of The Johns Hopkins University or The University of Minnesota.
1USDA, DAIRY 2007—PART III: REFERENCE OF DAIRY CATTLE HEALTH AND MANAGEMENT PRACTICES IN THE UNITED STATES, 2007, p. 141 (Sept. 2008),http://www.aphis.usda.gov/animal_health/nahms/dairy/downloads/dairy07/Dairy07_dr_PartIII_rev.pdf.
2Berge, A. C. B., Moore, D. A., Besser, T. E., & Sischo, W. M. (2009). Targeting therapy to minimize antimicrobial use in preweaned calves: effects on health, growth, and treatment costs. Journal of Dairy Science, 92(9), 4707–4714.
3Love, D. C., Davis, M. F., Bassett, A., Gunther, A., & Nachman, K. E. (2011). Dose imprecision and resistance: free-choice medicated feeds in industrial food animal production in the United States. Environmental Health Perspectives, 119(3), 279–283.
4Price, L. B., Stegger, M., Hasman, H., Aziz, M., Larsen, J., Andersen, P. S., Pearson, T., et al. (2011). Staphylococcus aureus CC398: Host Adaptation and Emergence of Methicillin Resistance in Livestock. mBio, 3(1), e00305–11–e00305–11. doi:10.1128/mBio.00305-11
5Withdrawal of Approval of New Animal Drug Application for Enrofloxacin in Poultry, Docket No. 2000N-1571, at 8 (Dep’t of Health & Human Servs., July 28, 2005)
6Reviewed by the author (MFD) in Davis, M. F., & Rutkow, L. (2012). Regulatory strategies to combat antimicrobial resistance of animal origin: recommendations for a science-based U.S. approach. Tulane Environmental Law Journal, 25, 327. A timeline is provided in this review.