Institute for Food Laws and Regulations

Scott Haskell is a PhD/DVM and food safety expert who teaches the online course “Global Animal Health, Food Safety, and International Trade” each fall semester, and "The Law of the Preventive Controls for Human Food Rule" each spring semester. Kris DeAngelo is an attorney, and teaches several courses with MSU's Institute for Food Laws and Regulations.

Right now, the world’s attention is focused on COVID-19 and its devastating effects. But another pandemic is eagerly awaiting and is relatively unchecked, and equally as bad if not worse: antimicrobial resistance (AMR). Antimicrobials refer to a group of substances that can destroy or slow the growth of microorganisms (e.g., antibiotics, antivirals, antifungals and antiparasitics). It should be noted that all antibiotics are antimicrobials but not all antimicrobials are antibiotics. 

AMR is reflective of ‘super bugs’ that do not respond to current antimicrobial agents. This AMR pandemic is already claiming 700,000 lives globally each year. Domestically, one person dies every 15 minutes due to antibiotic resistant organisms. In the United States alone, it is responsible for more than 35,000 preventable deaths every year. It is currently estimated that by the year 2050, on a global basis as many as ten million people per year could die from these infections (WHO, 2019). Antimicrobial resistance is a global crisis that risks reversing a century of progress in human and animal health. This should be scary news.

AMR has been declared by the World Health Organization (WHO) as one of the top ten global public health threats facing humanity in 2021. Antimicrobics used in both animals and humans are of importance to global food safety. The agriculture community and their production environments, as well as food supply sectors play a pivotal role when it comes to AMR. Sadly, in many regions of the world, animal agriculture antimicrobial use is far greater than in humans. This allows poor animal husbandry practices to flourish. AMR is threatening global food systems, food safety, food security, the environment, our public health systems, and food economics. 

The U.S. Center for Disease Control and Prevention (CDC) has noted that within animal slaughter and processing facilities, antimicrobial resistant species found on animals can contaminate meat and other animal products. Animal feces can contaminate meat from farm to slaughter and processing. Additionally, vegetables and fruit can become contaminated in any number of ways. Soil and water from contaminated domestic animal and wildlife waste or bird droppings can affect this produce.

According to a CDC report, of the 18 drug-resistant organisms highlighted as “alarming,” four are potentially fatal foodborne bacteria: E. coli, Campylobacter sp., Salmonella sp. and Shigella sp. This report also emphasizes that animals can serve as carriers or reservoirs of AMR species. Resistant species can contaminate our foods and those consuming these products can develop AMR infections.

Multiple factors can lead to AMR: overuse of antibiotics and antimicrobials (e.g., antimicrobial use or AMU), inappropriate use of specific products for the wrong infection and treatment, inappropriate drug use duration and dose, antimicrobials in wastewater and runoff where the agents may accumulate from manufacturing, disposal of expired products in landfills and sewerage, animal and human waste; utilizing antibiotics in food producing animals to mask poor production techniques.

A ‘One Health’ approach to address these shared antimicrobial health threats by recognizing the interconnection between people, animals, and our environment is the key concept to managing this issue. These bacteria, parasites and viruses are zoonotic, which implies that they can spread between people and animals or the reverse. The One Health approach to managing these issues is crucial to address new adverse disease threats that affect both people and animals. 

So, what accelerates the emergence and spread of antimicrobial resistance? AMR generally occurs naturally over time with many species of microbes, usually through genetic changes and mutations. AMR organisms are found in food, humans, animals, the environment (e.g., water, soil, and the atmosphere) and plants. They spread easily through food and contact. Important issues promoting the development of AMR include a lack of awareness and understanding of these drugs; the overuse and/or misuse of antimicrobials in medicine; lack of regulations for use and enforcement of legislation; general poor access to quality, affordable medicines, antiviral agents, diagnostic testing and vaccines in developing nations; poor disease prevention and high infection rates in humans and animals; and lack of access to clean water, and sanitation for food production facilities.

Legislation is a key component in trying to stop the abuse in global antimicrobial use. It also is important in regulating international antimicrobial use (AMU) and minimizing AMR. Within human antibiotic use, the FDA has defined medically important antibiotics in their Guidance for Industry (GFI) #152. All antibiotics in the classes listed in Appendix A of the FDA's GFI #152  are considered medically important in human medicine and should be utilized sparingly in animal species. This information is used in the Code of Federal Regulations (CFR) § 530.21 Prohibitions for food-producing animals.

In 2014 an executive order 3 CFR 13676 was enacted Combatting Antibiotic Resistant Bacteria. The development of a National Action Plan “was organized around five goals for collaborative action by the U.S. Government, in partnership with foreign governments, individuals, and organizations. The Plan takes a One Health approach, aiming to strengthen healthcare, public health, veterinary medicine, agriculture, food safety, and research and manufacturing. CDC addresses its role through its Antibiotic Resistance Solutions Initiative.” (CDC)

These executive goals are:

• Slow the Emergence of Resistant Bacteria and Prevent the Spread of Resistant Infections. 
• Strengthen National One Health Surveillance Efforts to Combat Resistance,
• Advance Development and Use of Rapid and Innovative Diagnostic Tests for Identification and Characterization of Resistant Bacteria.
• Accelerate Basic and Applied Research and Development for New Antibiotics, Other Therapeutics, and Vaccines.
• Improve International Collaboration and Capacities for Antibiotic Resistance Prevention, Surveillance, Control, and Antibiotic Research and Development.

What needs to be done legislatively NOW? Immediate action should occur within the federal government to combat AMR and resistant infections. Our government has made substantial headway with AMR and AMU both domestically and globally, but it is not enough. Policies and regulations need to be developed and enacted that are functional and powerful actions to deter AMR development. The United States needs to get involved.

• The United States as a nation must develop an agreed upon action plan to incentivize new research and development plans and assess the market sustainability of new antimicrobials. Industry, and the medical, veterinary, and pharmaceutical communities must buy into this action plan. Other countermeasures need immediate development as well.
• The federal government needs to budget funding to include AMR/AMU mitigation to support research and development, countermeasure development and implementation, and diagnostic services.
• Congress must streamline the ability for Medicare reimbursements for AMR related issues. Long term medical value must be placed on the enhancement of AMR mitigation. Immediate changes must take place.
• The federal and state governments must work diligently to promote the responsible and appropriate use of antimicrobials.
• A One Health (human, animal, and environmental spectrum) approach to surveillance must occur immediately. This One Health approach to disease surveillance for animal and human pathogens is extremely important to combat AMR.  Improved detection methods as well as the control of AMR in human and animal populations can only be achieved through a One Health approach to integrate data from multiple monitoring systems and diverse disease surveillance programs.  
• Funding should be made available to support AMR monitoring policies and enact reduction activities. CDC recommendations must be developed and put in place related to health policies, environmental monitoring, and laboratory diagnostics.
• As proposed in executive order 3 CFR 13676 establish State Antibiotic Resistance (AR) Prevention (“Protect Programs”) in all 50 states to monitor regionally important multi-drug resistant organisms and provide feedback and technical assistance to health care facilities for improved drug use.
• Elimination of the use of medically important antibiotics for growth promotion in food-producing animals. Again, all antibiotics in the classes listed in Appendix A of the FDA's GFI #152 are considered medically important to human medicine.
• There is an immediate need to develop research to support the development of alternatives to antimicrobials for use in food-producing animals. See the FDA call for proposals for research to support the development of alternatives to antimicrobials for use in food-producing animals.
• Adequate funding should be provided to develop antimicrobial alternatives, vaccine development and state of the art diagnostic testing.
• As a world leader, stepping up to a role to help combat AMR in lesser developed nations is essential for the US.
• Advocating for a joint effort to monitor for AMR within national health care and food industries.
• Enhance global surveillance and stewardship of drug use and environmental deposition.
• Work to develop a harmonized global database to collect quantitative and qualitative data on the use of antimicrobial agents in animals and humans.
• Improve antibiotic stewardship in agriculture.
• Strengthened regulatory and supply chain systems for quality global antimicrobial production. Transparency in the safety, quality, and product efficacy used in low- and middle-income countries is a must.

Antibiotic resistance is a global problem that will require a global solution. Learning to ‘play well with others’ is essential. Improved legislation and regulations are key to a successful confrontation to AMR and AMU. Antimicrobial pandemic planning and preparedness is key to correcting this foremost priority. We must invest in antimicrobial use and resistance patterns. Our government must listen.

Disclaimer.

References

CDC. Importance of One Health for COVID-19 and Future Pandemics. https://www.cdc.gov/media/releases/2021/s1103-one-health.html

CDC. U.S. Action & Events to Combat Antibiotic Resistance. https://www.cdc.gov/drugresistance/us-activities.html

CDC. U.S. National Action Plan. https://www.cdc.gov/drugresistance/us-activities/national-action-plan.html

FAO. Antimicrobial resistance- legislation  https://www.fao.org/antimicrobial-resistance/key-sectors/legislation/en/

FDA. Animal Products FDA Regulates. https://www.fda.gov/animal-veterinary/resources-you/animal-products-fda-regulates

FDA. Antibiotic resistance threats in the United States. 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf

FDA. Antimicrobial resistance. https://www.fda.gov/animal-veterinary/safety-health/antimicrobial-resistance

FDA. Antimicrobial Resistance Information from FDA. https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/antimicrobial-resistance-information-fda

FDA. Center for Veterinary Medicine (CVM). Supporting antimicrobial stewardship in veterinary settings goals for fiscal years 2019-2023 https://www.fda.gov/media/115776/download

FDA. GFI #152 Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to Their Microbiological Effects on Bacteria of Human Health Concern. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/cvm-gfi-152-evaluating-safety-antimicrobial-new-animal-drugs-regard-their-microbiological-effects

Jacobs, TG, et al. Assessing the impact of law enforcement to reduce over-the-counter (OTC) sales of antibiotics in low- and middle-income countries; a systematic literature review. BMC Health Serv Res 19, 536 (2019). https://doi.org/10.1186/s12913-019-4359-8

Landers, TF, et al. 2012 A Review of Antibiotic Use in Food Animals: Perspective, Policy, and Potential. Public Health Rep. 2012 Jan-Feb; 127(1): 4–22.

USDA. Antimicrobial resistance action plan. https://www.usda.gov/sites/default/files/documents/usda-antimicrobial-resistance-action-plan.pdf

WHO 2019 No Time to Wait: Securing the Future from Drug-Resistant Infections. https://www.who.int/docs/default-source/documents/no-time-to-wait-securing-the-future-from-drug-resistant-infections-en.pdfsfvrsn=5b424d7_6