Pharmacology Consult

Food animal production affects worldwide antibiotic resistance

There is currently a worldwide antibiotic resistance epidemic affecting patients of all ages, from all walks of life and in all areas of medicine. This growing public health concern limits treatment options and makes successful pharmacotherapy much more difficult.

Although hospital use of antimicrobials has been assumed to generate the highest risk of resistance and transmission, it is interesting to note that most antimicrobials are actually found in food animal production: Virtually all animals raised for food in the US today are given antibiotics to stimulate growth, prevent bacterial infections and maintain viability. Furthermore, approximately 70% of the antibiotics used in the US every year are administered to animals raised for food.

The relationship between antibiotics used in agriculture and human consequences is not a new concern, as the significance of antimicrobial use in animals and the development and dissemination of resistance have been debated for many years. In fact, several major health organizations, including WHO and the AMA, have stated that the farm-animal industry is contributing to potential unknown long-term risks for humans.

Kathryn Connor, PharmD, BCPS, BCNSP
Kathryn Connor, PharmD, BCPS, BCNSP

Unfortunately, there is still no consensus on this issue, but there is increased public and scientific interest in the administration of antimicrobials to animals. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including penicillins, expanded-spectrum cephalosporins, aminoglycosides, tetracyclines, sulfonamides and fluoroquinolones, among others.

Mechanisms and implications

The widespread use of sub-therapeutic and therapeutic antibiotics in food animal production has resulted in the emergence of antibiotic-resistant bacteria that can be transmitted to humans through the food chain. The transfer of antibiotic-resistant genes and selection for resistant bacteria in food animals are often multifactorial and can occur through a variety of mechanisms, including chromosomal mutations and the horizontal transfer of resistance determinants from mobile genetic elements.

Furthermore, these concerns extend beyond the agricultural field into the aquaculture environment: Antibiotics introduced into water via feed or that are used for the prevention and treatment of diseases in fish have been found to induce high levels of antibiotic-resistant bacteria in aquatic ecosystems.

The increasing incidence of antimicrobial-resistant pathogens has severe implications in the treatment and prevention of infectious diseases, including the emergence of community-associated methicillin-resistant Staphylococcus aureus with reservoirs of resistance in humans and animals in the community. One study at the University of California, Berkeley also linked eating beef to urinary tract infections in women.

Potential solutions, role of pharmacists

Although research has linked the use of antibiotics in agriculture to the emergence of antibiotic-resistant foodborne pathogens, it is still unclear whether this is significant enough to merit further regulation or restriction. To this end, it is important to accurately assess and evaluate the interactions between the hospital and community environments; improve surveillance for community-acquired resistance, including agriculture; and implement policies that prevent increases in community reservoirs of antibiotic resistance. Furthermore, scientific strategies aimed at inhibiting efflux pumps and eliminating plasmids may help restore therapeutic efficacy to antibiotics and reduce the spread of antibiotic-resistant pathogens through the food chain.

European countries have enacted legislation that mandates strict criteria for monitoring antimicrobial residues; the development of fast, reliable, sensitive testing methods is a priority there. Furthermore, multiple countries outside of the US have enacted or are considering implementing more stringent restrictions or bans on some types of antimicrobials used in food animal production. In some cases, these bans appear to have resulted in decreased prevalence of some drug-resistant bacteria.

Organic farming also deserves due consideration in this discussion, as its restrictions and additional requirements have shown to contribute to further effectiveness of antibiotics.

Infectious disease practitioners play a pivotal role in public health control, research and increased pharmacovigilance, especially in antibiotic stewardship — arguably the most effective tool in staving off antibiotic resistance. Efforts in antibiotic management and on education and risk-management in these areas would likely be invaluable to the issues at hand. Furthermore, opportunities for collaboration between infectious disease practitioners, regulatory agencies, the agricultural industry, etc., should be considered. These may include facilitation of appropriate antibiotic management programs, consistent treatment protocols, communication and outreach efforts that encourage information flow, including education on lack of forthcoming antimicrobials in the pipeline, etc.

As effective strategies for control of antimicrobial resistance are considered, it is crucial that scientific information provide the foundation for optimizing animal and human health and minimizing risks from antibiotic-resistant bacteria. Going forward as we consider these issues, it is likely that a multifactorial approach from many members of the health care community, including the collaboration of infectious disease practitioners helping to manage antimicrobials, will be needed to effectively limit the total amount of antimicrobials to address both animal welfare and public health needs.

For more information:

  • Barlow RS. J Appl Microbiol. 2008;104:651-658.
  • Bezanson GS. Int J Food Microbiol. 2008;127:37-42.
  • Brownlee C. The beef about UTIs. Science News. Jan. 7, 2010. Available at: www.sciencenews.org/view/generic/id/5782/title/The_Beef_about_UTIs. Accessed April 26, 2011.
  • Call DR. Anim Health Res Rev. 2008;9:159-167.
  • Diarra MS. Appl Environ Microbiol. 2007;73:6566-6576.
  • Diarrassouba F. J Food Prot. 2007;70:1316-1327.
  • Fricke WF. Appl Environ Microbiol. 2009;75:5963-5971.
  • Ghidán A. Acta Microbiol Immunol Hung. 2008;55:409-417.
  • Girardi C. Vet Res Commun. 2008;32(Suppl 1):S11-S18.
  • Leatherbarrow AJ. Environ Microbiol. 2007;9:1772-1779.
  • Mathew AG. Foodborne Pathog Dis. 2007;4:115-133.
  • McDermott PF. Anim Biotechnol. 2002;13:71-84.
  • McManus PS. Annu Rev Phytopathol. 2002;40:443-65.
  • Peng Y. J Dairy Res. 2008;75:491-496.
  • Reuters Medical News. Drug-resistant bacteria found in US meat. May 24, 2001. Available at: www.pmac.net/AM/DR_bacteria.pdf. Accessed April 26, 2011.
  • Rezzonico F. Antimicrob Agents Chemother. 2009;53:3173-3177.
  • Schwaiger K. Zoonoses Public Health. 2008;55:331-341.
  • Silbergeld EK. Med Clin North Am. 2008;92:1391-1407.
  • Steinman D. Diet for a Poisoned Planet: How to Choose Safe Foods for You and Your Family. New York: Harmony Books; 1990.
  • Walsh C. Curr Drug Targets. 2008;9:808-815.
  • Webster P. Lancet. 2009;374:773-774.
  • Yu D. Chemosphere. 2009;76:915-920.

Kathryn A. Connor, PharmD, BCPS, BCNSP, is a clinical pharmacy specialist and assistant professor of critical care at the University of Rochester Medical Center. Dr. Connor reports no relevant financial disclosures.

There is currently a worldwide antibiotic resistance epidemic affecting patients of all ages, from all walks of life and in all areas of medicine. This growing public health concern limits treatment options and makes successful pharmacotherapy much more difficult.

Although hospital use of antimicrobials has been assumed to generate the highest risk of resistance and transmission, it is interesting to note that most antimicrobials are actually found in food animal production: Virtually all animals raised for food in the US today are given antibiotics to stimulate growth, prevent bacterial infections and maintain viability. Furthermore, approximately 70% of the antibiotics used in the US every year are administered to animals raised for food.

The relationship between antibiotics used in agriculture and human consequences is not a new concern, as the significance of antimicrobial use in animals and the development and dissemination of resistance have been debated for many years. In fact, several major health organizations, including WHO and the AMA, have stated that the farm-animal industry is contributing to potential unknown long-term risks for humans.

Kathryn Connor, PharmD, BCPS, BCNSP
Kathryn Connor, PharmD, BCPS, BCNSP

Unfortunately, there is still no consensus on this issue, but there is increased public and scientific interest in the administration of antimicrobials to animals. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including penicillins, expanded-spectrum cephalosporins, aminoglycosides, tetracyclines, sulfonamides and fluoroquinolones, among others.

Mechanisms and implications

The widespread use of sub-therapeutic and therapeutic antibiotics in food animal production has resulted in the emergence of antibiotic-resistant bacteria that can be transmitted to humans through the food chain. The transfer of antibiotic-resistant genes and selection for resistant bacteria in food animals are often multifactorial and can occur through a variety of mechanisms, including chromosomal mutations and the horizontal transfer of resistance determinants from mobile genetic elements.

Furthermore, these concerns extend beyond the agricultural field into the aquaculture environment: Antibiotics introduced into water via feed or that are used for the prevention and treatment of diseases in fish have been found to induce high levels of antibiotic-resistant bacteria in aquatic ecosystems.

The increasing incidence of antimicrobial-resistant pathogens has severe implications in the treatment and prevention of infectious diseases, including the emergence of community-associated methicillin-resistant Staphylococcus aureus with reservoirs of resistance in humans and animals in the community. One study at the University of California, Berkeley also linked eating beef to urinary tract infections in women.

Potential solutions, role of pharmacists

Although research has linked the use of antibiotics in agriculture to the emergence of antibiotic-resistant foodborne pathogens, it is still unclear whether this is significant enough to merit further regulation or restriction. To this end, it is important to accurately assess and evaluate the interactions between the hospital and community environments; improve surveillance for community-acquired resistance, including agriculture; and implement policies that prevent increases in community reservoirs of antibiotic resistance. Furthermore, scientific strategies aimed at inhibiting efflux pumps and eliminating plasmids may help restore therapeutic efficacy to antibiotics and reduce the spread of antibiotic-resistant pathogens through the food chain.

European countries have enacted legislation that mandates strict criteria for monitoring antimicrobial residues; the development of fast, reliable, sensitive testing methods is a priority there. Furthermore, multiple countries outside of the US have enacted or are considering implementing more stringent restrictions or bans on some types of antimicrobials used in food animal production. In some cases, these bans appear to have resulted in decreased prevalence of some drug-resistant bacteria.

Organic farming also deserves due consideration in this discussion, as its restrictions and additional requirements have shown to contribute to further effectiveness of antibiotics.

Infectious disease practitioners play a pivotal role in public health control, research and increased pharmacovigilance, especially in antibiotic stewardship — arguably the most effective tool in staving off antibiotic resistance. Efforts in antibiotic management and on education and risk-management in these areas would likely be invaluable to the issues at hand. Furthermore, opportunities for collaboration between infectious disease practitioners, regulatory agencies, the agricultural industry, etc., should be considered. These may include facilitation of appropriate antibiotic management programs, consistent treatment protocols, communication and outreach efforts that encourage information flow, including education on lack of forthcoming antimicrobials in the pipeline, etc.

As effective strategies for control of antimicrobial resistance are considered, it is crucial that scientific information provide the foundation for optimizing animal and human health and minimizing risks from antibiotic-resistant bacteria. Going forward as we consider these issues, it is likely that a multifactorial approach from many members of the health care community, including the collaboration of infectious disease practitioners helping to manage antimicrobials, will be needed to effectively limit the total amount of antimicrobials to address both animal welfare and public health needs.

For more information:

  • Barlow RS. J Appl Microbiol. 2008;104:651-658.
  • Bezanson GS. Int J Food Microbiol. 2008;127:37-42.
  • Brownlee C. The beef about UTIs. Science News. Jan. 7, 2010. Available at: www.sciencenews.org/view/generic/id/5782/title/The_Beef_about_UTIs. Accessed April 26, 2011.
  • Call DR. Anim Health Res Rev. 2008;9:159-167.
  • Diarra MS. Appl Environ Microbiol. 2007;73:6566-6576.
  • Diarrassouba F. J Food Prot. 2007;70:1316-1327.
  • Fricke WF. Appl Environ Microbiol. 2009;75:5963-5971.
  • Ghidán A. Acta Microbiol Immunol Hung. 2008;55:409-417.
  • Girardi C. Vet Res Commun. 2008;32(Suppl 1):S11-S18.
  • Leatherbarrow AJ. Environ Microbiol. 2007;9:1772-1779.
  • Mathew AG. Foodborne Pathog Dis. 2007;4:115-133.
  • McDermott PF. Anim Biotechnol. 2002;13:71-84.
  • McManus PS. Annu Rev Phytopathol. 2002;40:443-65.
  • Peng Y. J Dairy Res. 2008;75:491-496.
  • Reuters Medical News. Drug-resistant bacteria found in US meat. May 24, 2001. Available at: www.pmac.net/AM/DR_bacteria.pdf. Accessed April 26, 2011.
  • Rezzonico F. Antimicrob Agents Chemother. 2009;53:3173-3177.
  • Schwaiger K. Zoonoses Public Health. 2008;55:331-341.
  • Silbergeld EK. Med Clin North Am. 2008;92:1391-1407.
  • Steinman D. Diet for a Poisoned Planet: How to Choose Safe Foods for You and Your Family. New York: Harmony Books; 1990.
  • Walsh C. Curr Drug Targets. 2008;9:808-815.
  • Webster P. Lancet. 2009;374:773-774.
  • Yu D. Chemosphere. 2009;76:915-920.

Kathryn A. Connor, PharmD, BCPS, BCNSP, is a clinical pharmacy specialist and assistant professor of critical care at the University of Rochester Medical Center. Dr. Connor reports no relevant financial disclosures.