The New York Academy of Sciences
Antibiotics in Food: Can Less Do More?
Posted January 18, 2017
Veterinarians treat animal diseases with many of the same antibiotics that physicians use to treat human diseases. Decades ago, though, farmers discovered that antimicrobial drugs can also cause animals to gain weight faster, increasing farms' efficiency and boosting profits. In theory, the chronic administration of antibiotics to billions of farm animals worldwide could increase bacterial resistance to these drugs. But does it, and if so, what should we do about it?
On June 3, 2016, the New York Academy of Sciences' Sackler Institute for Nutrition Science hosted Antibiotics in Food: Can Less Do More?, a day-long conference on the use of antimicrobial drugs in agriculture. The meeting's first session featured presentations about the use of antibiotics on farms around the world, both historically and today, and the measures policymakers have taken to address public concerns about these drugs. The second session explored the molecular biology of antibiotic resistance, the potential economic effects of restricting these drugs on farms, and the challenges of monitoring antimicrobial stewardship across diverse segments of the food industry.
Though scientists are still debating the relationship between veterinary antibiotic use and the rise of resistant human infections, attendees agreed that the available data, plus increasing public awareness of the issue, are giving scientists a unique opportunity to work with policymakers to improve both animal and human health.
Use the tabs above to find a meeting report and multimedia from this event.
Presentations available from:
H. Morgan Scott, Texas A&M University
Delia Grace, International Livestock Research Institute
Jaap A. Wagenaar, Utrecht University
Seamus Fanning, University College Dublin
Alan G. Mathew, Purdue University
David R. Wolfgang, Pennsylvania State University
Agnes C. Agunos, Public Health Agency of Canada
Stacy E. Sneeringer, USDA
William J. Hall, Wellcome Trust, United Kingdom Antimicrobial Resistance Review
How to cite this eBriefing
The New York Academy of Sciences. Antibiotics in Food: Can Less Do More?. Academy eBriefings. 2016. Available at: www.nyas.org/Antibiotics2016-eB
- 00:011. Introduction
- 2:412. Consumer knowledge and using research effectively
- 7:503. Aquaculture and antibiotics
- 12:054. Higher doses of antibiotics
- 18:475. Global investment in developing countries
- 24:166. Sustainable alternatives and solutions
- 28:527. Discussion of impacts of targets and success in the Netherland
- 00:011. Introduction
- 04:252. We need comprehensive action to re-invigorate the supply of new antimicrobials
- 8:513. We need to significantly reduce unnecessary demand for antimicrobials
- 12:004. Reducing demand and cutting inappropriate use must extend to animals too
- 16:435. Three priority areas for action this year and next step
- 00:011. Introduction: alternatives to antibiotics
- 9:122. Panel discussion: alternative approaches overview
- 16:083. Providing accurate and beneficial information to consumers
- 20:124. Animal husbandry best practices
- 25:255. Balancing economic consequences with environmental concerns
- 30:586. Drivers for new innovatio
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Agunos A, Léger D, Avery BP, et al. Ciprofloxacin-resistant Campylobacter spp. in retail chicken, western Canada. Emerging Infect Dis. 2013;19(7):1121–1124.
Agunos A, Waddell L, Léger D, Taboada E. A systematic review characterizing on-farm sources of Campylobacter spp. for broiler chickens. PLoS ONE. 2014;9(8):e104905.
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Fox EM, Wall PG, Fanning S. Control of Listeria species food safety at a poultry food production facility. Food Microbiol. 2015;51:81–86.
Herrero M, Havlík P, Valin H, et al. Biomass use, production, feed efficiencies, and greenhouse gas emissions from global livestock systems. Proc Natl Acad Sci USA. 2013;110(52):20888–20893.
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Mathew AG, Rattanatabtimtong S, Nyachoti CM, Fang L. Effects of in-feed egg yolk antibodies on Salmonella shedding, bacterial antibiotic resistance, and health of pigs. J Food Prot. 2009;72(2):267–273.
Stacy Sneeringer, James M MacDonald, Nigel Key, et al. Economics of antibiotic use in U.S. livestock production. USDA Economic Research Service—ERR200. November 2015.
Murphy CP, Fajt VR, Scott HM, et al. Scoping review to identify potential non-antimicrobial interventions to mitigate antimicrobial resistance in commensal enteric bacteria in North American cattle production systems. Epidemiol Infect. 2016;144(1):1–18.
Phongpaichit S, Liamthong S, Mathew AG, Chethanond U. Prevalence of class 1 integrons in commensal Escherichia coli from pigs and pig farmers in Thailand. J Food Prot. 2007;70(2):292–299.
Power K, Wang J, Karczmarczyk M, et al. Molecular analysis of OXA-48-carrying conjugative IncL/M-like plasmids in clinical isolates of Klebsiella pneumoniae in Ireland. Microb Drug Resist. 2014;20(4):270–274.
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Soehnlen MK, Kunze ME, Karunathilake KE, et al. In vitro antimicrobial inhibition of Mycoplasma bovis isolates submitted to the Pennsylvania Animal Diagnostic Laboratory using flow cytometry and a broth microdilution method. J Vet Diagn Invest. 2011;23(3):547–551.
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Speksnijder DC, Jaarsma DAC, Verheij TJM, Wagenaar JA. Attitudes and perceptions of Dutch veterinarians on their role in the reduction of antimicrobial use in farm animals. Prev Vet Med. 2015;121(3–4):365–373.
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Gary R. Acuff, PhD
Gary R. Acuff is currently a professor of food microbiology and director of the Texas A&M Center for Food Safety, where in 2001 he was designated a Texas AgriLife Research Faculty Fellow for research leadership. Acuff served as head of A&M's Animal Science department from 2004–2010. President of the International Association for Food Protection (IAFP) from 2007–2008, he was inducted as an IAFP Fellow in 2013 and named a fellow in the American Academy of Microbiology in 2014. Acuff obtained his BS in biology from Abilene Christian University and his MS and PhD in food science and technology from Texas A&M University. His research has focused on improving the microbiological quality and safety of red meat in all areas of production and utilization. Recent activities have centered on the effective use of surrogate bacteria for validation of process control in Hazard Analysis Critical Control Point systems.
Robert E. Brackett, PhD
Robert Brackett serves as Illinois Institute of Technology (IIT) vice president and director of the Institute for Food Safety and Health. Prior to joining IIT, Brackett served as senior vice president and chief science and regulatory officer for the Grocery Manufacturers Association, and at the FDA's Center for Food Safety and Applied Nutrition (CFSAN), where ultimately Brackett was appointed director. Brackett is a fellow in the International Association for Food Protection and American Academy of Microbiology and a member of the International Association for Food Protection, Institute of Food Technologists, the American Society for Microbiology, and the Food and Drug Law Institute. He has received the FDA Award of Merit, the FDA Distinguished Alumni Award, the Department of Health and Human Services Secretary's Award for Distinguished Service, and the William C. Frazier Food Microbiology Award. Brackett received his doctorate in food microbiology from the University of Wisconsin–Madison.
Sarah Marie Cahill, PhD
Food and Agriculture Organization of the United Nations
Sarah Cahill received her PhD in food microbiology from University College Dublin, Ireland. She subsequently joined the Food and Agriculture Organization of the United Nations in Rome, Italy where she currently works in the Office of Food Safety in FAOs Agriculture and Consumer Protection Department. Currently the FAO Secretariat, she is responsible for overseeing the provision of scientific advice on microbiological hazards in a wide range of foods, from fresh produce to meat and fish. She is an active participant in the Codex standard setting processes. Additionally, she has worked on the provision of scientific advice to other UN agencies (WFP, UNICEF) on the safety of specific foods destined for food insecure and vulnerable populations. Her work also focuses on increasing the accessibility of risk assessment and scientific advice to the FAO and Codex Membership.
Bruce Cogill, PhD
Bruce Cogill is a consultant in nutrition, food security and sustainable food systems. He was formerly research program leader for Nutrition and Marketing of Diversity, Bioversity International. He holds a PhD and Master's degrees from Cornell University, where he studied International Nutrition and Agricultural Economics. His experience includes appointments as chief of nutrition at USAID Washington, where he led the nutrition effort for the Feed the Future and the Global Health Initiative. He has contributed to strategy developments for large donors and served on technical committees and recently was on the Board of the Micronutrient Initiative, GAIN Alliance, and the Chair of the Steering Committee for the Health and Nutrition Tracking Service at WHO. He has appeared on television news programs and in print as an authority on international nutrition and sustainable diets and is the associate editor for nutrition for the Journal for Global Health: Science and Practice.
Jeffrey Farber, PhD
Jeff Farber is a professor in the department of food science at the University of Guelph, where he heads the master's in food safety and quality assurance program and is also director of the Canadian Research Institute for Food Safety. A past director of the Bureau of Microbial Hazards, in the Food Directorate of Health Canada, Farber has published over 150 papers and numerous book chapters, and edited four books. A long-time associate editor of the International Journal of Food Microbiology, he has served on numerous journal editorial boards. A past-president of the International Association for Food Protection, he is also a member and treasurer of the International Commission on Microbiological Specifications for Foods, as well as a member of the Agriculture, Food and Nutrition Working Group of the New York Academy of Sciences. He serves on the board of directors of the US-based Center for Produce Safety and was recently appointed to the USFDA Food Advisory Committee.
Gilles Bergeron, PhD
Gilles Bergeron has worked in international nutrition for more than 25 years. He has extensive experience in nutrition in the life cycle, food security, agriculture/nutrition linkages and monitoring and evaluation. A founding member and deputy director of the Food and Nutrition Technical Assistance (FANTA) project, he spent 18 years overseeing FANTA's work in policies and programs; nutrition and infectious diseases; maternal and child nutrition; agriculture/nutrition linkages and emergency nutrition response. Prior to joining FANTA, he spent six years as Research Fellow with the International Food Policy Research Institute (IFPRI) and three years with the Institute of Nutrition for Central America and Panama (INCAP) in Guatemala. He has operated in Africa, Latin America and Asia, and his work has been published in leading scientific journals such as The Lancet, Advances in Nutrition, World Development, the Journal of Development Studies, and Food and Nutrition Bulletin. He received his PhD in development sociology from Cornell University.
Mireille Mclean, MA, MPH
Mireille Mclean joined the Sackler Institute for Nutrition Science at the New York Academy of Sciences in 2011 as a Program Manager, and was later promoted to director. Her activities include managing the growing pool of research grants issued through the Sackler Institute's Research Funds, organizing multi-disciplinary workshops and symposia in the field of nutrition, and supporting the dissemination of research. Prior to this, she spent over 10 years doing fieldwork for several international NGOs intervening in crisis situations. In that role, Mclean defined and directed the implementation of programs in nutrition, health, food security and sanitation for vulnerable population groups in South East Asia, Africa and the Middle East; managed large grant programs for displaced populations and conducted a number of participatory research assessments and nutritional surveys. She holds an MA in Development Economics and International Development from the University of Sussex and a Master of Public Health from the Liverpool Faculty of Medicine.
Agnes C. Agunos, DVM, MSc
Public Health Agency of Canada
Agnes Agunos received her doctorate of veterinary medicine from the University of the Philippines and an MSc from the University of Guelph, Ontario. She is a diplomate of the American College of Poultry Veterinarians and core member of the Epidemiology and Diseases of Public Health Significance committees of the American Association of Avian Pathologists. Formerly, she served as the lead veterinarian for poultry at the Ontario Ministry of Agriculture, Food and Rural Affairs, and is a past president of the Ontario Association of Poultry Practitioners. In 2009, she joined the Public Health Agency of Canada as co-lead of the poultry farm components of the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) and FoodNet Canada, voluntary national surveillance programs monitoring antimicrobial use/resistance and pathogen prevalence. She collaborates with various poultry researchers across Canada and has published primary research and review articles on antimicrobial use and resistance in poultry.
Séamus Fanning, PhD
Séamus Fanning was appointed to the chair of Food Safety & Zoonoses at University College Dublin in 2002. He holds a PhD degree in molecular microbiology, and currently his research interests include the application of molecular methods to food safety, applied to the control of zoonotic food-borne bacteria and the protection of public health. A significant part of his work is related to the characterization of the genetic mechanisms contributing to multi-drug resistance emerging in bacteria of food-producing animal and human origin. Fanning is the Director of the UCD-Centre for Food Safety (UCD-CFS) and has also served as a member of a number of WHO/FAO expert groups. Fanning is a member of the editorial boards of Applied & Environmental Microbiology, Foodborne Pathogens & Disease, Journal of Food Protection, and Microbial Drug Resistance and is an editor for Research in Microbiology and FEMS Microbiology Letters.
Delia Grace, PhD
Delia Grace is an epidemiologist and veterinarian with 20 years of experience in developing countries. Currently, she leads research on zoonoses and foodborne disease at the International Livestock Research Institute in Kenya. Her research interests include emerging diseases, participatory epidemiology, gender studies and animal welfare. Her career has spanned the private sector, field-level community development and aid management, as well as research. She has lived and worked in Asia, west and east Africa and authored or co-authored more than 100 peer-reviewed publications as well as training courses, briefs, films, articles, and blog posts.
William J. Hall
Wellcome Trust, United Kingdom Antimicrobial Resistance Review (AMR)
William Hall is on secondment as a senior policy advisor to AMR from the UK Treasury, where he has worked as an advisor on government taxation and spending, advised on structural reforms to the UK banking system, and most recently led the work on the Scottish Referendum in the office of Danny Alexander, chief secretary of the Treasury. Through AMR, he is heavily involved in efforts to build an international consensus, as well as leading on a number of policy areas, including diagnostics, agriculture and vaccines. He is also a science policy fellow at the University of Cambridge.
François Malouin, PhD
François Malouin is a professor of microbiology at the Département de biologie at the Faculté des sciences of Université de Sherbrooke. He was recently appointed to the Comité d'experts scientifiques sur la résistance aux antibiotiques de l'Institut national de santé publique du Québec (2011–2015), a committee providing recommendations to the provincial government on the matter of antibiotic resistance. Malouin obtained his bachelor degree at Université de Sherbrooke, a masters in microbiology and immunology at Université de Montréal, a doctoral degree in medical microbiology at University of Calgary, and did postdoctoral training in the anti-infective research group at Lilly Research Laboratories. He was later recruited by Microcide Pharmaceuticals, Inc., and Iconix Pharmaceuticals, Inc. and co-founded Ulysses Pharmaceuticals. Currently at Université de Sherbrooke, his research projects aim at exploiting virulence genes for the development of new antibiotics, vaccines and non-antibiotic alternatives for applications in human and animal health.
James L. Marsden, PhD
James Marsden has over forty years' experience in the food industry with a strong background working with government officials, regulators, and for food companies, trade associations and in academia. He has advised the White House on food safety and nutrition and testified on numerous occasions to the US Congress, the US Food and Drug Administration and the US Department of Agriculture. After working for several food companies and technology providers, he served as vice president for scientific affairs at the American Meat Institute and president of the AMI Foundation. The author of numerous scientific publications, books, book chapters and articles on food safety, he also writes the popular blog Safety Zone. Marsden joined Chipotle in 2016 as the company's executive director of food safety, where he is responsible for directing the food safety programs at Chipotle Mexican Grills, Shop House restaurants and Pizzeria Locale. He was elected into the Meat Industry Hall of Fame in 2014.
Alan G. Mathew, PhD
Alan Mathew grew up on a grain and livestock farm in Indiana. He earned his BS in biology, MS and PhD in animal sciences, all at Purdue. During his graduate years and between earning his MS and PhD, Mathew co-managed the family's swine and grain operations. In 1993, Mathew joined the animal science faculty at the University of Tennessee, Knoxville, where he was ultimately promoted head in 2003. While at Tennessee, Mathew taught courses in animal science and the College of Veterinary Medicine and conducted research on foodborne pathogens and antibiotic resistance. In 2011, Mathew transitioned back to Purdue as head of animal sciences, for which he provides leadership to the department's research, teaching, and extension missions. He has served on the FDA's Center for Veterinary Medicine Advisory Committee, as president of the American Association of Animal Sciences Midwest Section, and is on the board of the US Pork Center of Excellence, among other advisory boards.
H. Morgan Scott, DVM, PhD
H. Morgan Scott is a graduate veterinarian holding a PhD in epidemiology and post-doctoral training in public health. A professor of epidemiology in the Department of Veterinary Pathobiology at Texas A&M University, he is interested in applying both epidemiological and ecological 'One Health' approaches to characterize and quantify the emergence, propagation, dissemination, and persistence of resistant enteric bacterial strains in integrated populations of animals, their food products, and humans in response to different antimicrobial management and treatment options.
Stacy E. Sneeringer, PhD
United States Department of Agriculture
Stacy Sneeringer is an economist in the Technology, Structure, and Productivity Branch, Resource and Rural Economics Division at the Economic Research Service in the USDA. She received a PhD in economics and a master's in demography from the University of California, Berkeley, and a BA in economics from Wesleyan University. Her research predominantly uses econometric methods to evaluate environmental and public health aspects of livestock agriculture in the U.S. She has published numerous articles in agricultural economics journals and delivered talks to academic departments, think tanks, and government agencies across the world.
Jaap A. Wagenaar, DVM, PhD
Jaap Wagenaar completed his PhD study at Utrecht University and the USDA-National Animal Diseases Center. In 1996, he started his research group at the Central Veterinary Institute in Lelystad, the Netherlands. From 2004–2006, he worked with WHO, the Centers for Disease Control and Prevention, and the USDA Western Regional Research Center. In 2006, he was appointed chair of clinical infectious diseases of veterinary medicine at Utrecht University. His research group focuses on Campylobacter and antimicrobial resistance. Currently, he is coordinating a large EU-project on antimicrobial resistance. He is member of the WHO Advisory Group on Integrated Surveillance of Antimicrobial Resistance group, WHO Global Foodborne Infections Network, and the scientific panel of the Netherlands Veterinary Medicines Authority, as well as involved in a major reduction of antimicrobial use in livestock. He is director of the WHO Collaborating Center for Campylobacter and of the OIE-reference laboratory for Campylobacteriosis, and acts frequently as an expert for WHO, FAO and OIE.
David R. Wolfgang, VMD, MPH
Pennsylvania State University
David Wolfgang is a graduate of the University of Pennsylvania School of Veterinary Medicine. He was in private veterinary practice, with an emphasis on food animals, from 1982 –1995. Since 1995, he has been director of field investigations and an extension veterinarian in the department of Veterinary and Biomedical Sciences at Penn State. He has been active in local and state veterinary organizations. He was president of the Pennsylvania State Veterinary Medical Association 2006, served as chair of the National Mastitis Council-Residue Avoidance Committee (2005–2009), and currently serves as chair of the Pennsylvania State Board of Veterinary Medicine. Recently, he returned to graduate school to earned his masters in public health from the Penn State College of Medicine–Hershey. His primary areas of professional emphasis include cost effective preventative health and diagnostic programs for livestock species, on farm food safety and quality, animal well-being, and continuing education programs for veterinarians.
Alan DoveAlan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism and blogs at http://dovdox.com.
H. Morgan Scott
Texas A&M University
Jaap A. Wagenaar
International Livestock Research Institute
Detailed information on global antibiotic use in animal agriculture, and its effect on human health, is hard to find.
Despite limited data, high-income countries are now moving to ban certain agricultural uses of antibiotics.
Rising global demand for meat drives increases in antibiotic use in low-income countries.
Tracking and publishing farm-level data led to reductions in antibiotic usage in the Netherlands.
The meat section of an American supermarket typically includes packages of beef, chicken, and pork, some proclaiming that the animals were "raised without antibiotics." What does that mean, and why does it matter? Those questions are at the center of a thorny, nuanced problem in the global food supply.
Antibiotics can be used therapeutically to treat bacterial infections in farm animals just as they are in humans, but decades ago farmers discovered that low doses of these drugs in an animal's regular feed can make it grow larger more quickly, boosting profits. However, several countries have banned the use of antimicrobials as growth promoters because of concerns that this regimen could be contributing to the rise in antimicrobial resistance that now threatens human health. As speakers at the Sackler Institute for Nutrition Science's conference Antibiotics in Food: Can Less Do More? showed, however, that hypothetical link—and many of the other scientific and policymaking questions around agricultural antibiotic use—remain unresolved.
Down on the farm
H. Morgan Scott started the conference with an overview of the history and current use of antibiotics in animal production. Between the 1930s and the 1960s, each new class of antimicrobial drug developed for humans soon found its way into animal agriculture, with only a few exceptions. Starting in the 1970s, however, new drug classes for humans have generally been kept off the farm.
Each new antimicrobial drug restarts a predictable cycle, beginning with regulatory approval and initial marketing, followed by the expiration of the drug's patent, a concomitant drop in price, increasing popularity, and inevitable microbial resistance that renders the drug less effective. "So long as there's a new antibiotic appearing every now and then, this is not necessarily a problem, but when the antibiotics stop appearing ... we have meetings such as the one we're having today," Scott said.
Regulators can approve animal antibiotics for curing or preventing a disease or reducing its severity, or for growth promotion. Because growth promotion involves feeding relatively low doses of medicines to animals over long periods of time, microbiologists and public health experts worry that this use could accelerate the rise of antibiotic-resistant bacteria. The European Union banned the use of antimicrobials for growth promotion in 2006, and the US is set to ban this use at the end of 2016. In much of the rest of the world, agricultural antibiotic regulation is inconsistent or nonexistent.
As policymakers push ahead, the data lag behind. "Generally speaking we don't know a lot about how antibiotics are used in animal agriculture," Scott said. In the US, the Animal Drug User Fee Act requires farmers to report their antibiotic use, and classifies the drugs based on their importance in human medicine. Those reports provide an overview of the quantities of antimicrobials used in agriculture, but don't detail why they were used. Meanwhile, regulators have focused on limiting the use of "critical" antibiotics, meaning those deemed most important in the clinic, but different regulatory bodies identify different drugs as critical.
Scott argues that the field needs help from social scientists to examine producers' motivations and behaviors around antibiotic use. Surveys of the animal agriculture industry reveal, for example, that veterinarians and farmers generally feel a moral obligation to treat ill animals. However, the two groups part ways on prevention, with most farmers saying that giving antibiotics to healthy animals to prevent disease is appropriate, and most veterinarians disagreeing. "We need to understand what some consider sacred and some consider profane in avoiding protracted conflict," said Scott.
Rich farm, poor farm
Delia Grace discussed the role of antimicrobials in agriculture in developing countries, which are by far the biggest—and most poorly studied—consumers of these drugs. Grace began with an overview of trends in the livestock industry worldwide, where skyrocketing demand for meat is driving huge increases in animal production. "Demand-driven things are much harder to change than supply-driven things," Grace said.
Indeed, the momentum of meat demand seems unstoppable. A staggering 98% of Earth's mammalian biomass now consists of humans and domesticated animals. People are moving out of poverty at accelerating rates, correlating perfectly with rising demand for animal protein. The richer people get, the more meat they want.
To feed this expanding appetite, farmers are turning to progressively more intensive animal husbandry and raising genetically inbred herds and flocks selected for maximum yields. "When you get animals which are very genetically similar, infection spreads very, very rapidly through them," Grace said. Big outbreaks and chronic infections in enormous animal facilities inevitably call for large amounts of antibiotics.
Most developing countries keep poor or no records of animal antibiotic use. To better understand the trends, Grace and her colleagues constructed a mathematical model based on countries' gross domestic products, which track closely with meat demand and the proportion of intensively kept animals, a term that covers all types of large-scale feeding and rearing operations. Assuming that intensive farms in low-income countries use antibiotics at rates similar to those in high-income countries, the investigators estimated a global demand of about 65,000 tons of antibiotics annually for animals. That compares to a global demand of about 100,000 tons for humans.
Looking at actual drug use in specific countries, however, reveals the model's limitations, suggesting that different antimicrobials are used in low-income countries. In Uganda, farmers observed that AIDS led to weight loss, and reasoned that the drugs prescribed to treat HIV would therefore cause weight gain. When the government began giving away antiretrovirals for free, farmers started feeding the compounds to their pigs. Meanwhile, Vietnam imports 6,000 kilograms of the asthma medication clenbuterol annually, but only 10 kilograms of it is used medically; the rest is fed to farm animals to increase lean meat production. In contrast, smallholder farms that support single or small groups of families in some parts of Africa suffer extensive animal losses from preventable and treatable diseases, because farmers can't get necessary antimicrobials. Depending on the country, farmers are likely using either too little medication or too much in their animals.
Grace cautioned that a single solution, such as a ban on antibiotics as growth promoters, won't fit all parts of the world: "It's a Goldilocks challenge if you like, it's not a linear problem, we need to address the 'too little' problem as well as the 'too much,' and our normal policy is very bad at that."
Jaap A. Wagenaar began his presentation by asking the audience one of the central questions behind the conference: to what extent does antimicrobial use in animal agriculture drive resistance in medically important bacteria? Wagenaar then explained that the answer probably varies dramatically for different antibiotics and bacteria. For example, Campylobacter infections in humans that are resistant to fluoroquinolone antibiotics are quite likely to have originated on a farm, while resistant Neisseria gonorrhoeae infections are highly unlikely to be related to antibiotic use in agriculture.
The effects of policy changes are similarly hard to pin down. The Netherlands banned the use of antibiotics as growth promoters in 2006, but Wagenaar explained that therapeutic use of the drugs on farms shot up immediately afterward. That led to an overall increase in animal antimicrobial use in the years following the ban.
A survey by the European Union in 2009 and 2010 revealed that the Netherlands had unusually high rates of animal antibiotic use, prompting widespread public concern. The news dovetailed with earlier reports of livestock-associated methicillin-resistant Staphylococcus aureus (MRSA) and an outbreak of Q fever that prompted the nation to slaughter all of its pregnant goats. "It was a clear signal that we had to do something on the veterinary side," Wagenaar said.
In 2010, the Netherlands established the Veterinary Medicines Authority agency, which tracks, analyzes, and publishes data from all 72,000 farms in the country, and defines benchmarks for antibiotic use by species. The Authority calculates the amount of antibiotics farmers are using in proportion to their herd sizes, and publishes the numbers. When a farm exceeds the benchmark for drug usage, purchasers voluntarily stop buying its products because they fear public rejection of them. "That economic driver works extremely well," Wagenaar said.
Looking at the results of the new system reveals that veterinary antimicrobial sales have declined by over 58% since 2009; importantly, fluoroquinolones and third and fourth generation cephalosporins—often considered among the most critical antibiotics in humans—are now reduced to minimal use in animals. At the same time, rates of antimicrobial resistance have declined somewhat in broiler chickens, pigs, veal, and dairy cows. A report released in March 2016 by the Veterinary Medicines Authority concluded that the new system has not harmed animal welfare.
Wagenaar credits the availability of good farm-level tracking systems for the country's success in reducing antimicrobial use. "When you do not have data, you have no idea what you're working with, but we had data on resistance and usage," because of the 2010 policy change, said Wagenaar.
Known knowns and known unknowns
After the first three presentations of the conference, the speakers returned to the stage for an extended Q&A with the audience. The group talked about the current public pressure for policy changes, especially in rich countries with comparatively minor food safety and antibiotic stewardship concerns. Grace reiterated her concern that these "worried well" nations might try to impose policies with unintended consequences on poor countries.
But regardless of what wealthy countries such as the Netherlands and the US do, speakers agreed that it will make little difference in the global use of antimicrobials. Developing countries already consume the bulk of antibiotics, and that proportion is rising as they eat more meat.
Responding to a question about the rates of clinical antimicrobial resistance, Wagenaar conceded that his group has not yet seen evidence that reducing the use of these drugs in animals has had an effect in humans.
Audience members also asked about research priorities in agriculture, such as developing vaccines, testing alternative husbandry practices, and identifying non-antimicrobial compounds that might have the same growth-promoting effects without driving antibiotic resistance. While the speakers generally supported such efforts, they pointed out that funding for research in general has not kept up with the need for new innovations.
University College Dublin
Alan G. Mathew
David R. Wolfgang
Pennsylvania State University
Agnes C. Agunos
Public Health Agency of Canada
Stacy E. Sneeringer
William J. Hall
Wellcome Trust, United Kingdom Antimicrobial Resistance Review
Antibiotic use in animals could promote the emergence of drug resistant bacteria that infect humans directly, or transfer resistance genes to bacteria that then infect humans.
The link between agricultural antimicrobial use and resistant human infections varies between bacterial species and geographical locations.
The US ban on animal antibiotic use for growth promotion might bankrupt small farms and worsen food safety problems.
The antibiotic resistance patterns in dairy cattle differ from those in beef cattle and defy simple explanations.
Canadian studies have found a small but noticeable correlation between antibiotic use on chicken farms and antibiotic-resistant human infections.
Many chicken farmers are contracted by large corporations and may not know whether their animals' feed contains antibiotics.
In the last several decades, antimicrobials have become less effective as growth promoters.
Pharmaceutical companies have little motivation to invest in developing new antibiotics.
Seamus Fanning started the meeting's second session with a discussion of the molecular biology of antibiotic resistance, and ongoing work to determine whether antimicrobial use in animals leads to treatment-resistant human clinical infections. At least in developed countries, rules requiring that animals not receive antimicrobials for a period of time before slaughter ensure that the compounds themselves are not in the meat. However, use of these drugs creates a selective pressure that could favor resistant strains, which could then contaminate meat and infect consumers. "The more selective pressure we put [on bacteria], the greater is going to be the risk that we're going to get an emergence of something [drug resistant]," Fanning said.
There's no doubt that antibiotic resistance is rising globally. Researchers project that by 2050, tens of millions of people could be dying annually from drug-resistant versions of currently treatable bacteria. There are two ways agricultural antibiotic use might augment that trend. In addition to the possibility that it could promote the emergence of drug-resistant bacteria that infect people directly through contaminated meat, antibiotic use could select for bacteria in animals with resistance genes that could then be transferred into other bacterial species that infect humans.
Bacteria routinely exchange genes on plasmids, circular pieces of DNA that remain independent of the host genome. Though researchers have hypothesized that resistance genes could be passed between bacteria in animals and humans, Fanning and his colleagues found that strains of the ubiquitous gut microbe E. coli in animals and humans carry distinct extended-spectrum beta-lactamase (ESBL) resistance genes. "So there appears to be a separation between what's happening in animals based on these genotypes and what's happening in humans," Fanning said. In both species, however, the ESBL resistance genes are on large plasmids that can move between bacteria, making the trait highly mobile.
Plasmids often carry multiple resistance genes. Fanning described the case of colistin resistance, which was originally found encoded by a chromosomal gene in bacteria. Looking at gene sequence databases, however, revealed that the gene also appears on large plasmids that carry genes for resistance to heavy metals, revealing a potential link between colistin and heavy metal resistance. "We use [heavy metals] in animal feed, we use them in organic agriculture, and heavy metals could co-select for not just [colistin resistance] but for several other antibiotic resistance genes, and nobody looks at it," said Fanning.
These and other results suggest that agricultural antimicrobial use may contribute to certain cases of resistance in human infections, but that the extent of the link varies widely between different bacterial species, types of clinical infections, and geographical locations.
Bringing home the bacon
Alan G. Mathew shifted the focus to the impact that reducing antimicrobial use could have on farmers. When the European Union banned the use of antibiotics for prophylaxis and growth promotion in 2006, the change had a particularly strong effect on pig farms. Young pigs got sick more often, production costs went up, and the price of pork rose temporarily. Similar problems may occur as the US ban on antimicrobial growth promotion goes into effect at the end of the year. "We can probably expect there's going to be some bumps in the road as we move that way, but they may be different kinds of bumps based on the way we produce pigs here," Mathew said.
To put the issue into context, Mathew described the finances of a typical American hog farm. These farms tend to operate at very small profit margins that make them highly sensitive to price fluctuations. Meanwhile, meatpackers base their payments on hog size, with pigs that are too small or too large bringing significantly lower prices than the ideal size. In this setting, even a slight change in the efficiency of animal growth could destroy a farm's profits.
Eliminating routine antibiotic use could also affect food safety. Mathew described a study comparing conventional and drug-free production of broiler chickens, young chickens that are raised for meat. The drug-free regimen substituted antimicrobials with essential oils, vaccines, and optimized animal husbandry. At the end of the growth cycle, the drug-free chickens were smaller, and were more likely to have Clostridium perfringens, a cause of serious foodborne illness, in their barns. "So we may have a food safety risk here to deal with [when] we take some of these promoters out of the feed," Mathew said.
Farmers who've eliminated antibiotics as growth promoters often rely on selling their products at a higher profit to distributors willing to pay a premium for "antibiotic-free" meats, eggs, or milk. In the case of a disease outbreak, these farmers might treat an entire herd with drugs, then sell that batch of products to a less choosy distributor at a lower price. Mathew argues that this may create an incentive to either withhold treatment from sick animals or not be fully truthful about the farm’s drug use. On a national scale, the farms most able to adopt drug-free practices will likely be the larger ones, perhaps forcing many smaller operations out of business.
David R. Wolfgang described the current, and coming changes to, applications of antibiotics on dairy farms. Unlike broiler chickens or beef cattle, which follow short, linear paths from birth to slaughter, dairy cows tend to remain on a farm for years, producing milk and consuming feed and antibiotics. Besides milk, one of the major byproducts is manure. Wolfgang explained that "in that [manure] are lots of antibiotics" and bacteria. The impact of that steady stream of antibiotics, however, is unclear.
On dairy farms, 60% of antibiotics are used to treat mastitis, usually by intramammary injection. Because dairy cattle enter milking parlors daily, they're relatively easy to medicate with high concentrations of short-acting antibiotics. In contrast, beef cattle spend much of their lives grazing on range land before being captured and moved to a finishing lot, so medication regimens for beeves tend to be longer-acting, with the active compounds present in the animal at lower doses. The two different protocols apply different selective pressures for antimicrobial resistance.
Studying a single dairy herd for several years, Wolfgang and his colleagues found a few bacterial clones that tended to dominate and persist in milk and mastitis-afflicted udders. The clones possessed some resistance genes for antibiotics that were never used on the farms, possibly highlighting the co-selection of resistance genes on plasmids or other mobile genetic elements.
Efforts to eradicate Salmonella spp. from the herd that Wolfgang's group studied failed consistently. "Some cows have Salmonella almost all the time, and there's a small group ... that never seems to have a positive [Salmonella test]," Wolfgang said. Drug resistance profiles showed a similarly broad distribution, with some resistance genes showing up commonly while others were completely absent; the resistance genes didn't correlate strongly with the antibiotics used on the farm.
Looking at a larger group of farms around Pennsylvania, Wolfgang and his colleagues found diverse bacterial colonization and antibiotic resistance patterns. "One of the challenges I think is when we take samples on farms, if you pick the right day and the wrong group of animals, you may get a completely different image of the resistance problems on that farm," Wolfgang said.
When a dairy cow stops producing milk, it usually gets sold to a beef packing plant. These cull dairy cows arrive at the slaughterhouse in small groups from across the country, and their diverse bacteria spread freely to other cattle at the plant. Wolfgang argues that changes in antibiotic stewardship at the farm level will mean little if they're not accompanied by more careful monitoring of the rest of the food supply chain.
Agnes C. Agunos presented data on Canada's efforts to reduce cephalosporin antibiotic use in broiler chickens. Third-generation cephalosporins are particularly important antibiotics in humans. Chicken farmers have also used similar drugs such as ceftiofurto treat infections in young chicks, but a 2003 study revealed that cephalosporin-resistant bacteria can persist and contaminate meat sold in supermarkets and butcher shops. A follow-up study in chicken hatcheries in Québec, a province recognized with high agricultural usage rates of these antibiotics, found all of the flocks carried at least one strain of cephalosporin-resistant bacteria. In Ontario, where farmers used these drugs much less, resistance was far less common.
The studies were among the first projects by the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS), within the Public Health Agency of Canada. CIPARS collects data on antibiotic resistance from farms, food processors, and retail food markets as well as medical clinics and hospitals. The integrated information allows scientists and regulators to identify trends in resistance among people and food animals.
With the baseline rates of cephalosporin resistance in chickens in Québec and Ontario established, CIPARS investigators next turned their attention to human data. Comparing the rates of cephalosporin resistance in Salmonella Heidelberg from chicken hatcheries and medical clinics over time revealed a troubling correlation: "Resistant isolates in chickens and humans are moving toward the same direction, however the association is much more pronounced or stronger in Québec," Agunos said. A voluntary withdrawal of the drugs from Québécois chicken farms correlated with a small but noticeable decline in drug resistance rates in bacteria from both chickens and humans.
In response to public pressure, the Canadian poultry industry voluntarily changed its animal husbandry guidelines in 2014, banning prophylactic use of antimicrobials identified as critical for humans. That group of compounds includes cephalosporins. The change prompted an immediate reduction in the use of cephalosporins, and CIPARS has found a decrease in cephalosporin resistance among bacterial isolates from some farms and retail stores. However, overall cephalosporin resistance in human Salmonella infections in Québec and Ontario has held steady. "This intervention has highlighted that in certain situations, reduction in resistance can happen quickly after the introduction of a use-reduction policy, and there are multiple impacts to measure," including rates of clinical infection with resistant bacteria, said Agunos.
Stacy E. Sneeringer and her colleagues study the economic effects of antibiotics in agriculture, with an eye toward predicting the financial impact of changing US regulations. While all meats, eggs, and dairy products sold in the US should already be free of antibiotic compounds, regulators are now focusing on the antibiotic-resistant bacteria that can persist on animal products after livestock have been treated. To combat this persistence, regulators and producers in the US are now phasing out the use of medically important antimicrobials for growth promotion and, in certain states, routine disease prevention.
The structure of modern American farming makes it hard to measure the extent of antibiotic use. In the broiler chicken industry, for example, big producers typically maintain contracts with independent farmers; the producer provides young animals and feed, and the farmer raises the animals. "What that means is that the contractor knows what's in the feed, but the farmer may not," Sneeringer said. As a result, surveys of farmers yield ambiguous data, with large proportions of respondents indicating they don't know whether they use antibiotics, and if so, whether they are used for growth promotion or disease prevention.
Nonetheless, the survey found that a large percentage of both chicken and hog producers already restrict their antimicrobial use to treatment. That may be because the growth-promoting effects of antibiotics have faded over time. Before the 1980s, adding antimicrobials to feed routinely yielded double-digit percentage increases in animal weight gain and feed efficiency, but over the last twenty years that figure has dropped to as low as one percent in some operations. Sneeringer hypothesizes that this decrease reflects improvements in animal husbandry, such that the antibiotics are no longer necessary for the animals to maintain peak health. "The industry has evolved. To the extent that the growth-promoting antibiotics were serving in a disease-preventing [role], that's no longer having the same effect as it used to," she explained.
Combining the survey results with the latest data on the impact of antimicrobial growth promotion, Sneeringer's team built a model to predict the effects of phasing out routine antibiotic use on chicken and hog farms. The results are reassuring, suggesting that if the underlying data are correct, withdrawing antibiotics from the feed supply should have little or no effect on the overall revenues and meat prices. "What we see is ... very limited impacts on prices and quantities," said Sneeringer. Because these are overall effects, they mask what may happen to individual farmers, like those of concern to Mathew.
Pushing and pulling against resistance
William J. Hall continued the economic theme with a look at the broader impact of antimicrobial resistance. Hall and a team of other economists and policy experts analyzed current trends, and determined that by 2050 antimicrobial-resistant infections could be a bigger cause of global deaths than cancer is today. Through this massive loss of life, plus medical costs and lost productivity, treatment-resistant microbes could drain as many as 100 trillion dollars from the global economy over the next 35 years. "The economic cost is huge, and we think this presents a stark case for action," Hall said.
To find ways to avoid that terrible cost, Hall and his colleagues looked at the underlying causes of antimicrobial resistance. Overuse of antibiotics in both humans and agriculture, and releases of drugs into the environment from sewage and pharmaceutical plants all appear to contribute to the problem, but researchers are still trying to determine which of those categories poses the biggest threat.
Meanwhile, the pharmaceutical industry's development of new antibiotics has faltered in recent years. "There's a clear market failure here, where in a very basic sense companies can make more money by investing in other areas" besides antimicrobials, Hall explained. To address the need for more antibiotic drug development, he recommends a combination of "push" and "pull" interventions by governments.
Push subsidies would help fund early-stage drug development, getting more antimicrobials into the drug approval pipeline. Pull funding would guarantee large payments or purchases to companies that bring new drugs to market. To cover the cost of the new interventions, Hall suggests one option would be charging a fee to pharmaceutical companies based on whether they invest in antibiotic development; those that are putting sufficient money into new antimicrobials might be exempt from such a fee, with the revenues used to finance the new subsidies.
New antibiotics will suffer the same fates as older ones unless companies and policymakers also work harder on antibiotic stewardship. It's often cheaper and easier for physicians to simply prescribe antibiotics without checking whether a patient's infection is susceptible to them. That increases the risk of promoting resistance. To break this pattern, Hall's team advocates mandatory diagnostic testing, in high income countries that can afford it, to reduce inappropriate antibiotic use.
Returning to the meeting's main topic, Hall concedes that the evidence for the impact of agricultural antimicrobial use remains unsettled. "There's obviously going to be a debate for many years to come about the extent of the threat to human health from antibiotic use in agriculture, but we feel that there is enough evidence now to start making steps," he said. In particular, he advocates setting targets for reducing the use of antimicrobials in agriculture, agreed in principle internationally, but set transparently by individual governments for thier own country. This would allow countries to develop their own policies to meet those targets.
After Hall's presentation, all of the speakers from the second session returned to the stage for an extended question session. The discussion began with a question about rising consumer demand for "antibiotic-free" foods. Sneeringer explained that it is still hard to pinpoint how much more people are willing to pay for such claims, though her group is now collaborating with supermarkets to collect data on that.
The lack of data on other aspects of antimicrobial resistance clearly frustrated other speakers and many members of the audience, and the group talked about the difficulties of reaching international agreements on drug use when many nations don't even track their current usage rates. Nonetheless, Hall expressed optimism that if the global community can agree on reduction targets, many nations could implement monitoring programs relatively easily.
An even bigger mystery is what effect the huge quantities of antibiotics in agricultural waste have on the soil microbiomes around farms. Fanning pointed to one recent study that did a preliminary analysis of the changes, but added that, "we don't understand what causes that adaptive mechanism within bacteria to cause some [antibiotic resistance] to be really problematic and others that are more transient."
H. Morgan Scott
Texas A&M University
James L. Marsden
Chipotle Mexican Grill
Francois Malouin introduced the meeting's final discussion session with a brief overview of alternatives to antimicrobials in agriculture. Researchers are now exploring the use of natural extracts from plants as growth promoters, immunomodulators and vaccines for disease prevention, and probiotics to help animals adapt to new feed regimens. However, all of these approaches are either in early developmental stages or showing relatively modest effects.
Malouin then turned the floor over to the audience and his two co-panelists, James L. Marsden and H. Morgan Scott. Marsden explained the difficulties the Chipotle restaurant chain had in finding pork raised without antibiotics, and talked about the growing consumer demand for such products.
All three speakers discussed the challenge of keeping industry marketing claims grounded in reality, especially when many prominent commentators in the food business promote dubious ideas. Marsden recommended that scientific organizations take a more active role in public discussions of food safety and nutrition.
Despite their diverse backgrounds, speakers and members of the audience largely agreed that antimicrobial stewardship in agriculture is at a crossroads. As Hall said in his presentation, "there's a lot of momentum at the moment, but if we don't have some sort of [regulatory] agreements this year it really feels like we might lose that momentum."
To what extent does agricultural antibiotic use drive resistance in human infections?
What effect will new antimicrobial stewardship rules have on farmers?
How much more are consumers willing to pay for meats raised without antibiotic growth promoters?
Can improvements in animal husbandry replicate the effects of growth-promoting drugs?
Will restricting antibiotics in agriculture improve human health?
What would motivate developing countries' farmers to reduce their use of antimicrobials?