Taking on Antimicrobial Resistance

The development of antibiotics is one of the greatest discoveries of humankind, resulting in countless lives saved from the devastation of infectious diseases.

Antimicrobials are important for modern animal agriculture and have been widely used for the prevention and control of animal diseases. Recently, the value of these “wonder drugs” has diminished due to the drastic increase in antimicrobial resistance, threatening public health and raising the specter of multibillion dollar medical costs and economic losses.

Antimicrobial resistance also is an ecosystem problem impacting the health of humans, animals and the environment. Antibiotic-resistant bacteria can develop in the digestive system of humans and livestock receiving antibiotics. There also is concern humans may be exposed to the resistant bacteria from livestock through food, the environment (water, soil, air) or by direct human-animal contact.

To address the challenge, in 2014 the White House issued the “National Strategy for Combating Antibiotic-Resistant Bacteria,” which calls for national efforts to combat antimicrobial resistance pathogens. In 2015, the World Health Organization endorsed a global action plan to mitigate the problem.

Collaborating to combat resistance Iowa State University has a group of diverse, highly experienced scientists working on a broad range of topics related to antimicrobial resistance. In 2015, a university-wide antimicrobial resistance initiative was established involving approximately 60 faculty members across several colleges and USDA National Center for Animal Health scientists.

Additional researchers and health professionals from several other Midwest institutions joined the effort and are helping to develop new interdisciplinary research projects. There are now more than 100 researchers involved in addition to Iowa State University faculty and staff.

“We want to continue to expand our initiative into a larger regional and national consortium, which we propose to call the Antimicrobial Resistance Consortium,” says Paul Plummer, associate professor of veterinary diagnostics and production animal medicine. “The initiative will take a systems-oriented approach so the biology and ecology of organisms are understood within the context of crop and livestock production and social, economic, environmental and other factors.”

Hongwei Xin, assistant dean for research in the College of Agriculture and Life Sciences, says stakeholders must work together to ensure guidelines are followed and emergence of resistance is monitored.

“Antibiotics contribute to antimicrobial resistance and impact people, animals and the environment. Trying to fix the blame for the global antibiotic resistance pandemic on a single source or use is contrary to the broad, systems approach required to make progress,” says Xin. “Critical research is needed on transmission of antimicrobial-resistant organisms through the environment, contact and food.”

Multi-pronged approach to mitigation

Interdisciplinary teams of researchers have numerous projects underway providing valuable information on the transport of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes in the livestock food chain and the effect of manure application timing and management on the presence of antibiotic-resistant bacteria.

In one such project, researchers received a nearly $1 million grant from the U.S. Department of Agriculture’s National Institute of Food and Agriculture (USDA-NIFA) to advance the technological tools used to detect antimicrobial resistance and form strategies to slow its spread.

Led by Adina Howe, an assistant professor of agricultural and biosystems engineering, the three-year project brings together researchers from Iowa State University, the USDA and Grinnell College. The team will improve a new technology called DARTE-QM, which it designed to efficiently sequence the genes of microbes. They will gather manure, soil and water samples from swine operations and use DARTE-QM to sequence genes associated with resistance in the samples.

The team will determine which genes may allow antimicrobial resistance to develop and persist in the environment. The researchers also will look at what production practices and environmental factors, such as drought or flooding, contribute to the propagation of resistant genes.

“We want to identify control points where we see reservoirs of resistance,” says Michelle Soupir, an associate professor of agricultural and biosystems engineering and a contributor to the project. “Once we do that, we can help determine mitigation efforts.”

Reducing resistance on farm

Members of the DARTE-QM research team, including Soupir, Howe and Thomas Moorman, scientist at the USDA National Laboratory for Agriculture and the Environment and affiliate associate professor of agronomy, are working with Dan Andersen to consider practical mitigation efforts for reducing the spread of resistance in agricultural environments.

Andersen is an assistant professor of agricultural and biosystems engineering. In addition to the USDA-NIFA grant, much of their work is funded by National Pork Checkoff dollars. They’re comparing effects of alternative swine manure treatment and storage.

“Manure is a great fertilizer resource on a farm. Livestock production is a critical component of sustainability as the majority of nitrogen, phosphorus and potassium we feed ends up in manure and needs to be recycled,” says Andersen. “Managing microbes for soil health, including the presence of antibiotic-resistant bacteria, is an evolving science.”

Andersen says each method under consideration in their collaborative research shows potential for reducing antibiotic-resistant bacteria in swine manure. Mitigation efforts under consideration include:

• Anaerobic digestion—This system could include capturing the resulting natural gas for energy.
• Two-phase manure storage—Holding manure longer in two different basins allows the natural microbial community more time to reduce the presence of antibiotic-resistant bacteria.
• Addition of Ionophore—Narasin (a brand of the antibacterial agent Ionophore) is an approved feed additive designed to reduce methane in swine manure, and it may hold potential for reducing the presence of resistant bacteria as well.
• Centrifugation—Separating liquid manure from solid has shown antibiotic-resistant bacteria tend to stay in the solids.
• Separating solid manure from liquid as manure is removed from facilities— This is planned for inclusion at Iowa State University’s proposed new facilities.

“Preliminary results show two-phase storage reduces the presence of antibiotic-resistant bacteria, and centrifugation can remove as much as 100 percent under high speeds for an extended time,” Soupir says.

Andersen says some of the strategies are showing promise for an additional benefit: the reduction of odor by 10-15 percent.

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Key Points from ISU Experts on Antibiotic Resistance In Livestock

Iowa State University faculty have broad expertise and experience in the area of antibiotic use and antibiotic resistance in livestock and poultry, and work closely with stakeholders on addressing these issues. The following are key points to consider from the perspective of Iowa State researchers, veterinarians and extension specialists.

• The U.S. meat supply is safe. The USDA Food Safety Inspection Service oversees the safety of meat.
• Veterinarians and livestock producers strive for prudent, judicious use of antibiotics and have established guidelines and training materials to help ensure antimicrobials are only used when necessary and are administered appropriately.
• Antibiotic use remains an important option for reducing animal suffering. Veterinarians carry out proper treatment plans for animal health and animal welfare, including the use of antibiotics to reduce suffering and death from treatable illnesses.
• Approximately 30 percent of animal antibiotics are not used in human medicine. This class of drugs, called ionophores, is used to prevent and control coccidia, a family of disease-causing parasites. Ionophores are not associated with the development of antibiotic resistance that would impact human health.
• Comparing livestock antibiotic use to humans can be misleading. The statement “80 percent of antibiotics are used in animals” often is a common claim cited in news media and by some organizations. That statistic lacks context, and the FDA has cautioned against comparing human and animal numbers. Differences in scale exist between livestock and people in terms of dosing and volume used.
• Antibiotics that are deemed medically important for humans have been restricted for use in animals to treat, prevent or control disease. In 2013, the FDA called on animal drug manufacturers to stop labeling their products for promotion of animal growth and to change the labeling to require veterinary oversight when they are used for therapeutic purposes. No antibiotics that are defined as medically important for use in humans are used for growth promotion; their use is limited to treatment, prevention and control of animal disease under the direct supervision and monitoring of veterinarians.
• The FDA rigorously evaluates new livestock antibiotics. Before final approval, the FDA is required to assess the safety of animal drugs to ensure low risk for antimicrobial resistance transmission to humans. This measure also ensures the continued safety of meat products.
• U.S. poultry farms have monitored antimicrobial resistance since 2014. The poultry industry, in collaboration with the USDA National Antimicrobial Resistance Monitoring System, began collecting on-farm bacteria samples to monitor antimicrobial resistance. The goal of this ongoing study is to monitor antimicrobial use and resistance over time.
• New, research-based alternatives to antibiotics exist. The implementation of research-based technologies—including improvements in the engineering of animal housing, the use of effective vaccinations, improved nutrition and genetic selection—is allowing the livestock and poultry industries to emphasize alternative approaches to improving efficiency that replace the use of antibiotics for growth promotion.

— Paul Plummer, associate professor, veterinary diagnostics and production animal medicine; Qijing Zhang, associate dean for research and graduate studies, College of Veterinary Medicine; Hongwei Xin, assistant dean for research, College of Agriculture

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Learn more:

Iowa State University Antimicrobial Resistance Consortium

American Veterinary Medical Association Resources on Antibiotic Use

Antimicrobial Resistance and Food and Drug Administration Guidance Documents