Poisonous Poultry:

1. Poisonous Poultry: Sub-therapeutic use of antibiotics in meat production and antibiotic-resistant bacteria. By Anandi Ehman and Tyler Jacobson

2. Stance: The sub-therapeutic use of antibiotics in food producing animals is causing an increase in the prevalence of antibiotic-resistant bacteria.

3. The issue: • Food-borne pathogens account for: 76 million diseases, 325,000 hospitalizations and 5,000 deaths annually in the United States

4. This issue and antibiotic resistance: • 25000 patients died due to multi-drug resistant bacteria in 2008 in the EU • Antibiotic-resistant bacteria are one of the leading causes of a recent increase in infectious disease deaths in the United States(HIV is the other) Trend for Penicillin-Resistant (MIC  2 mg/ml) S. pneumoniae in the US (1988-2002) % of Isolates Resistant to Penicillin

5. Antibiotic resistance is widespread:

6. Antibiotic Resistance is Common and Increasing:

7. Antibiotic Resistance is Common and Increasing:

8. Historical Aspects: • 3000 BC- use of molds by Ancient Egyptians to treat infection • 1674- Anton Von Leeuwenhoek creates lens for microscope • 1800’s- Germ Theory of Disease • 1877- Robert Koch discovers how to best grow cells in culture • 1928- Discovery of Penicillin

9. Historical Aspects continued: 1945 - Alexander Flemming claims that the misuse of penicillin could lead to “the selection and propagation of mutant forms of bacteria resistant to the drug,” 1946 - 14% of staphylococci strains resistant to penicillin

10. Historical Aspects continued: • 1950 - use of antibiotics spread to livestock • 1966-1970 - reports showing multi-drug resistant organisms transmissible between humans and animal • 1969 - Swann Report in UK bans many antibiotics • 1972 - FDA releases statement suggesting sub-therapeutic resistance of in food be stopped • 1998 - WHO recommends use of antibiotics as growth promoters be ceased • 1998 - Demark bans use of all antibiotics used in humans from use in food animals

11. What causes antibiotic resistance? • Mutation of bacteria gives rise to resistant forms • Treatment with antibiotics strongly selects for resistant bacteria • Resistant bacteria become more prevalent

12. What causes antibiotic resistance? • Over-prescription/over-availability of antibiotics • Incomplete dosages of antibiotics • Incorrect antibiotics for a particular disease • Prophylactic application • Use of antibiotics in food producing animals

13. Types of resistance mutations:

14. How does resistance spread? • One major danger 0f antibiotic resistance is how quickly it spreads through bacterial populations • Bacteria can transmit resistance between even distantly related species through multiple mechanisms • Genes for antibiotic resistance are often housed on plasmids, smaller rings of DNA not part of the bacterial chromosome

15. How does resistance spread? • Antibiotic resistance can be shared through transformation, transduction, and conjugation.

16. How does resistance spread?

18. How does resistance spread?

19. Why worry about resistance in bacteria that infects animals? • Antibiotics used in animals are not the same as those used in humans • Antibiotics are divided into classes • Antibiotics used in animals often come from the same classes as those used in humans • Resistance to a specific antibiotic often increases resistance against others in same class because they have similar mechanisms of function

21. Who is using sub-therapeutic antibiotics?

22. Why keep using antibiotics? • Meat industry creates 4.4 million jobs directly, 6.2 million indirectly in the US • Meat industry indirectly produces $832 billion per year in the US: 6% of GDP • Antibiotics as growth promoters improve the feed efficiency and growth rate of animals • Their use helps lower food costs and increase supply • Limitations would have “little or no effect” on prevalence of antibiotic resistant bacteria in humans

23. Why keep using antibiotics? • Some farmer advocacy groups claim that it allows chickens to “be the best they can be” • Can help developing nations create steady food supply and prevent shortages • Antibiotic usage in food animals is not the only source of resistance

24. Economic Issues:

25. Economic Issues: • Food production would decrease only slightly • Enough food would still be produced, but total costs would increase • The cost per European consumer is estimated to be between $4.85 and $9.72 per year

26. Economic Issues • Cost per consumer is estimated to increase $.05 per pound of pork for US consumers, about $11 per year • Total costs in the US per year are estimated to be $748 million • Estimated cost of resistance is $4-5 billion per year in 2001 • A 1995 Office of Technology Assessment report to Congress concluded that 6 common resistant bacteria cost about 1.3billion per year

27. Economics: • The economic detriments from sub-therapeutic use of antibiotics are largely externalities • Healthcare and missed work costs due to multi-drug resistant bacteria in the EU was 1.5 billion Euros ($2.25 billion USD) • Total cost of illness and death from Salmonella in US is $2.5 billion per year

28. Economic Costs: • Creating a new antibiotics costs between $500 and $800 million per drug

29. Externalities associated with antibiotic resistance:

31. Scientific Aspects: • E. coli resistant to nourseothricin arose within two years of its introduction as a growth promoter in pigs in Eastern Germany • Prior to introduction, tests showed no resistance was present • E. coli resistant to nourseothricin were found in farmers within 10 years, resulting in higher incidences of urinary tract infections • Nourseothricin resistance found in Salmonella and other strains of E. coli, including shiga-toxin producing E. coli within 12 years • Other studies have found similar increases

33. Political and Cultural Issues: • Antibiotics are banned Denmark and Sweden, and many are limited in the EU compared to their use in the US • Different cultural attitudes as to whether regulation is the government’s job contribute to the differences • Companies present in both Canada and the United States have different policies for farms run in each country • There are differences even among the opinions and practices of US farmers, such as the growing organic movement

35. Moral issues: • Infections from multi-drug resistant bacteria have been shown to cause 25000 deaths per year in the EU • 1.2 million cases of Campylobacter per year in the US are drug resistant • Of these 326,000 are resistant to two or more drugs • Is increased profitability worth the health or lives of citizens?

36. The Precautionary Principle:

37. Potential Solutions: • Stop sub-therapeutic application of antibiotics • Optimized dosing schedules • Monitoring and regulating antibiotic usage • Prebiotics, probiotics and competitive exclusion • Bacteriocins • Exploiting facultative metabolisms of bacteria • Bacteriophage therapy • Vaccines

38. Future Implications: • 90.2% of chicken in America tested positive for E. coli in 2009 • 1.4 million Americans infected with Salmonella per year • 2.4 million Americans infected with Campylobacter per year • “Antimicrobial farms had significantly lower resistance”

39. Future Implications:

41. Our Position: Continued use of sub-therapeutic levels of antibiotics in food producing animals will only increase the prevalence of antibiotic-resistant bacteria in humans.

42. Citations: • ALPHARMA Animal Health. Straight Talk About Antibiotic Use in Food Animal Production. (2010, October). For the Record, 9(4), 1-4. Retrieved February 14, 2011, from http://www.alpharma.com/pdf/For_The_Record_Oct2010.pdf • AMI. (2010, April). AMI Fact Sheet: The Economic Impact of the Meat Industry in the U.S. In American Meat Industry. Retrieved February 13, 2011, from http://www.meatami.com/ • Ancient Egypt. (2011, February 16). In Wikipedia. Retrieved February 21, 2011, from: http://en.wikipedia.org/wiki/Ancient_Egypt. • Antibiotic. (2011, February 16). In Wikipedia. Retrieved February 21, 2011, from: http://en.wikipedia.org/wiki/Antibiotic. • Bacteria. (2011, February 16). In Wikipedia. Retrieved February 21, 2011, from: http://en.wikipedia.org/wiki/Bacteria. • Banerjee, M. R., & Yesmin, L. (2001). Biotechnology. Encyclopedia of Biotechnology in Agriculture and Food, 116-119. • Bischoff, K. M., Callaway, T. R., Edrington, T. S., Genovese, K. J., Crippen, T. L., & Nisbet, D. J. (2005). Antimicrobial Use in Food Animals: Potential Alternatives. Encyclopedia of Animal Science, 45-47.

43. Burch, D. (2005, January). Problems of antibiotic resistance in pigs in the UK. In The Pig Site. Retrieved February 13, 2011, from http://www.thepigsite.com/articles/?Display=1266 • Cassanova, L.; Sobsey, M.D. Human And Environmental Health Risks from Antimicrobially Resistant Bacteria in Food Animal Production Systems. 2006. 667-720. From: Animal Agriculture and the Environment. Edited by: Rice, J.M.; Caldwell, D.F.; Humenik, F.J. ASABE Press, St. Joseph, MI. 2006. • CDC. (2003, August 14). Infectious Disease Mortality in U.S. 1900-1996. In CDC: National Center for Infectious Diseases. Retrieved February 13, 2011, from http://www.cdc.gov/ncidod/osr/site/about/graph.htm. • DiMasi, J. A., Hansen, R. W., & Grabowski, H. G. (2003). The price of innovation: new estimates of drug development costs. Journal of Health Economics, 22, 151-185. Retrieved February 14, 2011, from http://www.ncbi.nlm.nih.gov/pubmed/12606142 • Dufresne, M. (2007). Truth Be Told. In Canadian Poultry Magazine. Retrieved February 13, 2011, from http://www.canadianpoultrymag.com/content/view/1947/38/ • Germ Theory of Disease. (2011, February 16). In Wikipedia. Retrieved February 21, 2011, from: http://en.wikipedia.org/wiki/Germ_theory_of_disease. • Grave, K.; Jensen, V.F.; McEwen, S.; Kruse, H. Monitoring of Antimicrobial Drug Usage in Animals: Methods and Applications. 2006. 375-395. From: Antimicrobial Resistance in Bacteria of Animal Origin. Edited by: Aarestrup, F.M. ASM Press, Washington, D.C. 2006.

44. Hayes, D.J.; Jensen, H.H.; Fabiosa, J.F. What would happen if Over-the-Counter Antibiotics were Banned( in Swine Rations)? CARD: Center for Agricultural and Rural Development. (2000). 6(3). Retrieved: February 20, 2011, from: http://www.card.iastate.edu/iowa_ag_review/summer_00/over_the_counter.aspx. • Keep Antibiotics Working. (2003, December). The Basics: Antibiotic Resistance. In Keep Antibiotics Working. Retrieved February 13, 2011, from http://www.keepantibioticsworking.com/new/basics.cfm. • Lees, P.; Concordet, D.; Aliabadi, F.S; Toutain, P.L. Drug Selection and Optimization of Dosage Schedules To Minimize Antimicrobial Resistance. 2006. 49-71. From: Antimicrobial Resistance in Bacteria of Animal Origin. Edited by: Aarestrup, F.M. ASM Press, Washington, D.C. 2006. • Levy, S. B. (2002). The Antibiotic Paradox (2nd ed.). Cambridge, MA: Perseus Publishing. • Louis Pasteur. (2011, February 16). In Wikipedia. Retrieved February 21, 2011, from: http://en.wikipedia.org/wiki/Louis_Pasteur#Germ_theory_of_disease. • McGowan, J.E. Economic Impact of Antimicrobial Resistance. CDC: Emerging Infectious Diseases. (March 2001). 7(2). Retrieved: February 11, 2011, from: http://www.cdc.gov/ncidod/eid/vol7no2/mcgowan.htm. • Mead, P. S., Slutsker, L., Deitz, V., McCraig, L. F., Bresee, J. S., Shapiro, C., & Griffin, P. M. (1999, September). Food-Related Illness and Death in the United States. Emerging Infectious Diseases. Retrieved February 13, 2011, from http://www.cdc.gov/ncidod/eid/vol5no5/mead.htm.

45. "NOAH: The Present." National Office of Animal Health. NOAH, n.d. Web. 20 Feb. 2011. http://www.noah.co.uk/focus/present.htm. • Prescott, J. F. "History of Antimicrobial Usage in Agriculture: an Overview." Antimicrobial Resistance in Bacteria of Animal Origin. Copenhagen: Danish Institute for Food and Veterinary Research, 2006. 19-27. Print. • Reyes-Herrera, I.; Donoghus, A.M. Novel Strategies for the Preharvest Control of Campylobacter in Poultry. 2010. 11-26. From: Perspective on Food-Safety Issues of Animal-Derived Foods. Edited by: Ricke, S. C. and Jones, F.T. The University of Arkansas Press, Fayetteville, A.K. 2010. • Roberts, M.C. The Evolution of Antibiotic Resistant Microbes in Foods and Host Ecosystems. 2009. 231-229. From: Food Borne Microbes-Shaping the Hose Ecosystem. Edited by: Jaykus, LA.; Wang, H.H.; Schlesinger, L.S. ASM Press, Washington DC. 2009. • Rogers, L. "The Denmark Experience." Save Antibiotics. The PEW Chartiable Trusts, n.d. Web. 20 Feb. 2011. http://www.saveantibiotics.org/resources/DenmarkExperience.pdf. • Rollo, S. N., Norby, B., Bartlett, P. C., Scott, H. M., Wilson, D. L., Fajit, V. R., & Linz, J. E. (2010, January 15). Prevalence and patterns of antimicrobial resistance in Campylobacter spp isolated from pigs reared under antimicrobial-free and conventional production methods in eight states in the Midwestern United. Journal of the American Veterinary Medical Association, 236(2). Retrieved February 12, 2011, from http://www.ncbi.nlm.nih.gov/pubmed/20074013.

46. Union of Concerned Scientists. (2009, September 12). Antibiotic Resistance and Food Safety. In Union of Concerned Scientists: Citizens and Scientists for Environmental Sollution. Retrieved February 14, 2011, from http://www.ucsusa.org/food_and_agriculture/solutions/wise_antibiotics/food-safety-antibiotics.html. • Union of Concerned Scientists. (2009, September 12). Myths and Realities about Antibiotic Resistance: FAQ’s. In Union of Concerned Scientists: Citizens and Scientists for Environmental Sollution. Retrieved February 14, 2011, from http://www.ucsusa.org/food_and_agriculture/solutions/wise_antibiotics/food-safety-antibiotics.html. • U.S. Congress, Office of Technology Assessment, Impacts of Antibiotic-Resistant Bacteria, OTA-H-629 (Washington, DC: U.S. Government Printing Office, September 1995). • White, D.G.; McDermott, P.F. Antimicrobial Resistance in Food-Borne Pathogens. 2009. 231-265. From: Food Borne Microbes-Shaping the Hose Ecosystem. Edited by: Jaykus, LA.; Wang, H.H.; Schlesinger, L.S. ASM Press, Washington DC. 2009. • World Health Organization. (2011, February). Race against time to develop new antibiotics. In World Health Organization. Retrieved February 13, 2011, from http://www.who.int/bulletin/volumes/89/2/11-030211/en/index.html

47. Image Citations: • Figure 1: • CDC. (2003, August 14). Infectious Disease Mortality in U.S. 1900-1996. In CDC: National Center for Infectious Diseases. Retrieved February 13, 2011, from http://www.cdc.gov/ncidod/osr/site/about/graph.htm • Figure 2: • Weber, D.J. (n.d.) Trend for Penicillin-Resistant (MIC  2 mg/ml) S. pneumoniae in the US (1988-2002). [Bar Graph retrieved from Slideshow]. University of North Carolina at Chapel Hill. NC, USA. Retrieved from: www.unc.edu/depts/spice/AntibioticResistant-DJW20041112.ppt. • Figure 3: • Edens, F. W. (2003, August). Antibiotics sensitivity of E. coli and Salmonellae isolated from poults suffering from poult enteritis and mortality syndrome. [Chart] Retrieved from: Edens, F. W. (2003, August). An alternative for antibiotic use in poultry: probiotics. RevistaBrasileira de CiênciaAvícola, 5(2). doi:10.1590/S1516-635X2003000200001 • Figure 4: • M.R.S.A. (n.d.). [Image] In Cartoon Stock. Retrieved February 14, 2011, from http://www.cartoonstock.com/directory/s/superbug.asp

48. Figure 5: • Burch, D. (2005, January). Development of fluoroquinolone (enrofloxacin) resistance in Escherichia coli from pigs. [Line Graph] Retrieved from: Burch, D. (2005, January). Problems of antibiotic resistance in pigs in the UK. In The Pig Site. Retrieved February 13, 2011, from http://www.thepigsite.com/articles/?Display=1266 • Figure 6: • Percentage of E. coli Isolates from retail meats resistant to selected antibiotics (Reproduced from NARMS, 2002). (2006). [Table of resistance]. From: Cassanova, L.; Sobsey, M.D. Human And Environmental Health Risks from Antimicrobially Resistant Bacteria in Food Animal Production Systems. 2006. 667-720. From: Animal Agriculture and the Environment. Edited by: Rice, J.M.; Caldwell, D.F.; Humenik, F.J. ASABE Press, St. Joseph, MI. 2006. • Figure 7: • Increase in Antibiotic Resistance. (March 1, 2011). [Line graph of resistance]. From: Vollmer, S. RTP panels address rogues gallery of multi-drug resistant bacteria. Science in the Triangle. March 1, 2011. Retrieved March 13, 2011, from: http://scienceinthetriangle.org/2011/03/rtp-panels-address-rogues-gallery-of-multidrug-resistant-bacteria/.

49. Figure 8: • Percentage of isolates from retail meats resistant to selected antibiotics (reproduced from NARMS, 2002). (2006). [Chart of resistance]. From: Cassanova, L.; Sobsey, M.D. Human And Environmental Health Risks from Antimicrobially Resistant Bacteria in Food Animal Production Systems. 2006. 667-720. From: Animal Agriculture and the Environment. Edited by: Rice, J.M.; Caldwell, D.F.; Humenik, F.J. ASABE Press, St. Joseph, MI. 2006. • Figure 9: • Percentage of E. faecium isolates from retail meats resistant to selected antibiotics (reproduced from NARMS, 2002). (2006). [Chart detailing percentages of resistance]. From: Cassanova, L.; Sobsey, M.D. Human And Environmental Health Risks from Antimicrobially Resistant Bacteria in Food Animal Production Systems. 2006. 667-720. From: Animal Agriculture and the Environment. Edited by: Rice, J.M.; Caldwell, D.F.; Humenik, F.J. ASABE Press, St. Joseph, MI. 2006. • Figure 10: • Thanks to Penicillin... He will come home. (1944). [Image]. From: Explore PA History. Retrieved February 14, 2011, from: http://explorepahistory.com/displayimage.php?imgId=4243.

50. Figure 11: • How antibiotic resistance evolves. (2007). [Diagram]. From: Science Blogs. Retrieved February 13, 2011, from: http://scienceblogs.com/mikethemadbiologist/2007/03/a_good_diagram_of_how_antibiot_1.php. • Figure 12: • Untitled. (January 3, 2008). [Diagram of antibiotic resistance]. From: Answers to Genesis. Retrieved March 12, 2011, from: http://www.answersingenesis.org/articles/nab/is-natural-selection-evolution. • Figure 13: • Unfortunately, no amount of antibiotics will get rid of your cold. (December 15, 2008). [Image]. From: Microbiology Bytes: The latest news about microbiology. Retrieved February 13, 2011, from: http://www.microbiologybytes.com/blog/category/bacteria/page/4/. • Figure 14: • Untitled. (2008). [Image of prescription symbol]. From: Smart Now. Retrieved February 23, 2011, from: http://www.smartnow.com/page/4777. • Figure 15: • Weber, D.J. (n.d.) Mechanisms of resistance. [Diagram retrieved from slideshow]. University of North Carolina at Chapel Hill. NC, USA. Retrieved from: www.unc.edu/depts/spice/AntibioticResistant-DJW20041112.ppt.