Antibiotics Overuse: Why Healthcare Should Care about Agriculture Use

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Antibiotics Overuse: Why Healthcare Should Care about Agriculture Use October 7, 2010 Webinar sponsored by the American Medical Association, in partnership with Health Care Without Harm and Kaiser Permanente Moderator: Preston Maring, M.D., Associate Physician-in-Chief, Kaiser Permanente Medical Center Oakland Presenter: David Wallinga, MD. MPA directs www.healthyfoodaction.org, a project of the Institute for Agriculture and Trade Policy, and serves on the steering committee of www.keepantibioticsworking.org. He also is a Wm. T. Grant Foundation Distinguished Fellow in Food Systems and Public Health, University of MN. In his work, Dr. Wallinga uses a systems lens to shed light on the health impacts our food and agriculture practices and policies, including the Farm Bill. For a decade, his work has focused on antibiotics fed to healthy animals, arsenic used to grow chickens faster and mercury contamination of HFCS, among other topics. He has degrees from Dartmouth College, Princeton University and the University of MN Medical School. Presenter: Diane Imrie, MBA, RD is the Director of Nutrition Services at Fletcher Allen Health Care. A Registered Dietitian, with 20 years in the field of nutrition and health care food service, Diane has facilitated the purchase and incorporation of local foods into the menu at Fletcher Allen. Those efforts resulted in Fletcher Allen receiving an honorable mention on the 2006 list of top ten Green Hospitals in America. Diane has spoken on the topic of sustainability at several national teleconferences, and Fletcher Allen has been recognized in many diverse publications, from Food Service Director magazine to the Maine Organic Farmer. She holds a Bachelor of Nutrition from McGill University, and an MBA from the University of Vermont. Presenter: Robert Martin is a senior officer at the Pew Environment Group and previously was the Executive Director of the Pew Commission on Industrial Farm Animal Production, a two year study funded by The Pew Charitable Trusts by a grant to Johns Hopkins Bloomberg School of Public. The charge to the Commission was to recommend solutions to the problems caused by concentrated animal feeding operations in the areas of public health, the environment, rural communities, and animal welfare. The Commission s final report, Putting Meat on the Table: Industrial Farm Animal Production in America, was release on April 28, 2008.

October 7, 2010 David Wallinga, MD, MPA HealthyFoodAction@iatp.org Wm. T Grant Foundation Distinguished Fellow, Food Systems and Public Health

The imperative No New FDA Drug Approvals 16 14 12 10 8 6 4 2 0 1983-1987 1988-1992 1993-1997 1998-2002 2003-2007 2008-2009 Spellberg, CID 2004; Boucher, CID 2009 (modified)

The imperative Running out of antibiotics that work Without effective action, treatments for common infections will become increasingly limited and expensive and, in some cases, nonexistent. Source: www.cdc.gov/ drugresistance/actionplan/ No pipeline!

The imperative Bacteria that cause food poisoning, like Campylobacter & Salmonella, are increasingly resistant to multiple antibiotics sometimes used to treat them Rising FQ-resistance among C. jejuni in human isolates MN data NARMS data Sources: Data on MN quinolone resistant C. jejuni from Smith KE et al. 1999. Other data on FQ-resistant C jejuni from NARMS. See Gupta A et al. 2004.

The imperative Emerging infections.mrsa, VRE, FQ-res infections Methicillin-resistant S. aureus Methicillin resistant signals resistance to other clinically important β-lactam antibiotics (penicillins,( cephalosporins, and carbepenems) Leading cause of hospital-associated associated infections ~1.5% colonized with MRSA. J Infect Dis 2006, 193, (2), 172-9. 18,000 deaths, 94,000 infections from MRSA in 2005. J Infect Dis 2008;197:1226-34. Image: http://trouble.philadelphiaweekly.com/archives/mrsa220207_400x379%5b1%5d.jpg

Fundamentals Resistance Antibiotic use + Reservoirs Extent of antibiotic use Prevalence ( reservoirs( reservoirs ) ) of resistance genes Levy S. Scientific American. March 1998 Darwin Natural selection

Fundamentals Resistance genes make the proteins that protect bacteria from antibiotics Physically-linked linked resistance genes

Fundamentals Ecological reservoirs of resistance The exchange of genes is so pervasive the entire bacterial world can be thought of as one huge multicellular organism in which the cells interchange their genes with ease. Levy S. 1998. Scientific American

Fundamentals Ecological reservoirs of resistance Hospitals Livestock farms The human gut The exchange of genes is so pervasive the entire bacterial world can be thought of as one huge multicellular organism in which the cells interchange their genes with ease. Levy S. 1998. Scientific American Fish ponds Communities Food supply

What we know about animal antibiotics Widespread antibiotic use is integral to much (but not all) of the industrial-style food animal production that predominates, worldwide. = Aarestrup FM, Wegener HC, Collignon P. Resistance in bacteria of the food chain: epidemiology and control strategies. Expert Rev. Anti Infect. Ther. 2008, 6(5):733-750.

What we know Science consensus August 30th Dr. Hugh Auchincloss, NIAID Principal Deputy Director,, Letter to Keeve Nachman, PhD, Johns Hopkins University Bloomberg School of Public Health: NIAID NIAID does find that the overall weight of evidence to date links antibiotic use in food animals with antibiotic resistance in humans. July 13 th CDC Director Thomas Frieden, MD, MPH, Letter to Chairman Frank Pallone, Subcommittee on Health, House Energy and Commerce Committee: To be clear, the Centers for Disease Control and Prevention (CDC) finds that there is a compelling body of evidence to establish a clear link between antibiotic use in animals and antibiotic resistance in humans.

What we know Science consensus Antibiotic use in animal agriculture DOES contribute to rising resistance transmitted to humans www.keepantibioticsworking.com/new/indepth_keyevid.cfm

What we know Science consensus Aarestrup FM et al. Expert Rev. Anti Infect. Ther. 2008, 6(5):733-750. Price L et al. Env Health Perspect. 2007 Smith DL et al. PLoS Medicine 2005 Shea KM. Pediatrics 2004 Angulo FJ et al. 2004. J. Vet. Med Anderson AD. Microb. Drug Resist 2003 Wegener H. Current Opinion in Microbiology 2003 Joint FAO/OIE/WHO Expert Workshop on Non-Human Antimicrobial Usage & Antimicrobial Resistance, 2003 NAS/IOM. Microbial Threats to Health.. 2003. Including MRSA! www.keepantibioticsworking.com/new/indepth_keyevid.cfm

What we know Aarestrup FM, Wegener HC, Collignon P. Resistance in bacteria of the food chain: epidemiology and control strategies. Expert Rev. Anti Infect. Ther. 2008, 6(5):733-750. Very large quantities of antibiotics are used in industrialized livestock. Industry, IOM, NGO estimates 1,2,3 agree: 20 to 30 million lbs per year Darwin 1. Institute of Medicine (1998), Antimicrobial Resistance: Issues & Options, Forum on Emerging Infections. www.nap.edu 2. Animal Health Institute (2002), Press Release dated September 30, 2002, accessed at http://www.ahi.org. 3. Union of Concerned Scientists. (2001). Hogging It! Estimates of Antimicrobial Abuse in Livestock. www.ucsusa.org

What we know Therapeutic Use : Example: Cephalosporins Extended spectrum antibiotics (ceftriaxone, cefepime) Important last lines of defense against severe, systemic Salmonella or E coli infections, other resistant infections. Widely used in food animals Ceftiofur = 3 rd gen ceph widely used in cattle, poultry wordlwide Cefquinome = 4 th gen ceph, used in Europe

U.S. Department of Health and Human Services, National Antimicrobial Resistance Monitoring System/Enteric Bacteria (NARMS/EB) Salmonella Annual Veterinary Isolates Data, U.S. Department of Agriculture, www.ars.usda.gov/main/docs.htm?docid=6750&page=4, 2006. Therapeutic Use : Ceftiofur-resistant resistant Salmonella in animals

What we know Therapeutic Use Non therapeutic Growth promotion / feed efficiency Prophylaxis / disease control Non-rx Healthy, non- exposed animals Just in case cover

What we know Abx. use by country can vary 10-fold

Best estimates 71% of all U.S. antimicrobials are fed routinely to beef cattle, poultry & swine Percentage of Total US Antibiotic Use 71% 8% 15% 6% Source: Union of Concerned Scientists, Hoggin It, 2001

What we know Very large quantities of antibiotics are used in industrialized livestock. These antibiotics are often identical or belong to the same classes as human antibiotics.

Aarestrup et al. 2008; FDA Green Book 2006 About ½ of antimicrobials added to feed FDA previously approved many feed additives without considering the potential for resistance are of medical importance Human antibiotic class Penicillins Tetracyclines Amingoglycosides Streptogramins Macrolides Clindamycin (lincosamides) Polypeptides Sulfonamides Arsenicals U.S.-approved feed-additive antibiotic(s) Penicillin G procaine Chlortetracycline, Oxytetracycline Spectinomycin Virginiamycin Tylosin, Erythromycin, Tilmicosin, Oleandomycin Lincomycin, apramycin Bacitracin Sulfanitran, Sulfadimethoxine, Sulfamethazine, Sulfaquinoxaline, Sulfathiazole, Neomycin sulfate Roxarsone, arsanilic acid, nitrarsone

Aarestrup et al. 2008; FDA Green Book 2006 About ½ of antimicrobials added to feed are of medical importance Human antibiotic class Penicillins Tetracyclines Amingoglycosides Streptogramins Macrolides Clindamycin (lincosamides) Polypeptides Sulfonamides Arsenicals U.S.-approved feed-additive antibiotic(s) Penicillin G procaine Chlortetracycline, Oxytetracycline Spectinomycin Virginiamycin Tylosin, Erythromycin, Tilmicosin, Oleandomycin Lincomycin, apramycin Bacitracin Sulfanitran, Sulfadimethoxine, Sulfamethazine, Sulfaquinoxaline, Sulfathiazole, Neomycin sulfate Roxarsone, arsanilic acid, nitrarsone

Aarestrup et al. 2008; FDA Green Book 2006 FDA previously approved many feed additives without considering the potential for resistance Human antibiotic class Penicillins Tetracyclines Amingoglycosides Streptogramins Macrolides Clindamycin (lincosamides) Polypeptides Sulfonamides Arsenicals U.S.-approved feed-additive antibiotic(s) Penicillin G procaine Chlortetracycline, Oxytetracycline Spectinomycin Virginiamycin Tylosin, Erythromycin, Tilmicosin, Oleandomycin Lincomycin, apramycin Bacitracin Sulfanitran, Sulfadimethoxine, Sulfamethazine, Sulfaquinoxaline, Sulfathiazole, Neomycin sulfate Roxarsone, arsanilic acid, nitrarsone

What we know Very large quantities of antibiotics are used in industrialized livestock. These antibiotics are often identical or belong to the same classes as human antibiotics. Darwin These conditions favor selection, persistence and spread of antibiotic-resistant bacteria capable of causing infections in both animals and people.

Antibiotic use in food animals transmits resistance to people via contaminated food, other routes Antibiotics Animals Via FOOD White et al., 2001. NEJM 345(16): 1147-54 (salmonella in ground meat); Molbak et al., 1999, NEJM (fatal salmonella in Denmark); Johnson JR et al. J Infect Dis. 2006;194[1]:71-78) (food-linked UTI) HUMANS (General Populace) Bacteria

Antibiotic use in food animals transmits resistance to people via contaminated food, other routes Antibiotics Animals Bacteria Via FOOD White et al., 2001. NEJM 345(16): 1147-54 (salmonella in ground meat); Molbak et al., 1999, NEJM (fatal salmonella in Denmark); Johnson JR et al. J Infect Dis. 2006;194[1]:71-78) (food-linked UTI) Salmonella Antibiotic use in food animals may account for as much as 90% of Salmonella resistance. Angulo F et al. 2000; IOM 1989 Campylobacter FDA estimates: 153,580 Americans developed fluoroquinolone (Cipro) resistant Campy from contaminated chicken. 66 FR 6623-6624 (01/22/01), using 1999 data E coli HUMANS (General Populace) Cipro-resistant resistant E coli infections in humans may be imported from chickens. Johnson J et al. JID 2006 A new, deadly (ESBL-producing) E coli strain now affects 30,000 British annually. One quarter of foreign retail chickens in UK supermarkets carry it. Collignon P, Aaerstrup. 2007

Antibiotic use in food animals transmits resistance to people via contaminated food, other routes Antibiotics Animals Via FOOD White et al., 2001. NEJM 345(16): 1147-54 (salmonella in ground meat); Molbak et al., 1999, NEJM (fatal salmonella in Denmark); Johnson JR et al. J Infect Dis. 2006;194[1]:71-78) (food-linked UTI) HUMANS (General Populace) Bacteria Via WORKERS Levy 1976, NEJM, 295(11): 583-588 (worker study); Lyons et al., 1980, JAMA 243(6): 546-7 (nursery outbreak). Price et al., 2007, Environ Health Perspect 115:1738 1742. Smith TC et al., 2009, PLoS ONE 4(1) Dutch hog farmers 760X more likely colonized with MRSA than the public. Voss, A.; Loeffen, F., Bakker, J. et. Al. Emerg. Infect. Dis. 2005. Human MRSA traceable to farm animals (hogs, cattle) from zero ( 02) >20% ( 06) Van Loo et al. Emerging Infectious Diseases, December 2007.

Antibiotic use in food animals transmits resistance to people via contaminated food, other routes Antibiotics Animals Via FOOD White et al., 2001. NEJM 345(16): 1147-54 (salmonella in ground meat); Molbak et al., 1999, NEJM (fatal salmonella in Denmark); Johnson JR et al. J Infect Dis. 2006;194[1]:71-78) (food-linked UTI) HUMANS (General Populace) Bacteria Via WORKERS Levy 1976, NEJM, 295(11): 583-588 (worker study); Lyons et al., 1980, JAMA 243(6): 546-7 (nursery outbreak). Price et al., 2007, Environ Health Perspect 115:1738 1742. Smith TC et al., 2009, PLoS ONE 4(1) Via ENVIRONMENT Via ENVIRONMENT Chee-Sanford et al., 2001. Applied Env. Microbiology. 67(4): 1494-1502 (tetracycline resistance genes in groundwater and soil bacteria). Chapin A et al., 2005. EHP.

What to do Curb antibiotic overuse, 1976 2003 The rise in frequency of resistant organisms in our environment is the obvious result of antibiotic usage.. All areas of antibiotic usage deserve critical evaluation. Dr. Stuart Levy, NEJM 1976; 295:583 Substantial efforts must be made to decrease inappropriate overuse of antimicrobials in animals and agriculture as well." Smolinski MS, Hamburg MA, Lederberg J, editors. Microbial threats s to health: emergence, detection, and response. Washington: Institute of Medicine icine. 2003.

What to do Curb antibiotic overuse Self-regulation Market-led change Policy options Stricter regulation Federal legislation

Curbing antibiotic use Quebec, 2005 Declining ceftiofur resistance in E coli and Salmonella bacteria in chickens, humans following withdrawal of extralabel use in Quebec hatcheries Irwin R (Public Health Agency of Canada)

Curbing antibiotic use Denmark ( 98-99), Sweden (1986) kg active compound 250,000 200,000 150,000 100,000 50,000 0 Total Antibiotic Use 54%, 1994-2001 1990 1992 1994 1996 1998 1999 2000 2001 Eliminating the routine use of antibiotics in livestock reduces Treatment Growth Promoters Total Antimicrobials human health risks without significantly harming animal health or farmers incomes. 32 Source: DANMAP 2001 WHO 2003. Wegener HC. Curr Opin Micro 2003.

Can food animals be produced in numbers without routine antibiotics?

The Journey of Sustainable Food at Fletcher Allen Diane Imrie, MBA, RD

Reduction of Antibiotics

Food Category 2008 Goal 2009 Goal 2010 Goal Poultry Status: Beef Status: Fish and Seafood Status: Eggs Status: Cheese Status: Pork Status: Purchase a minimum of 20% sustainably raised poultry Not achieved due to lack of availability. Purchase 100% sustainable ground beef. Complete. Evaluate current supply, develop plan and begin to implement. Complete and implemented. Evaluate options available. Complete. Research options and implement two rbst free (and local if possible) cheeses per year. Not achieved due to cost. Reduce the amount of pork purchased. Complete. Purchase an additional 20%. New source negotiated for target quantity of chicken and turkey. Evaluate other cuts of beef and implement change as required. Local source for all top round achieved. Next will be stew beef. Complete implementation and reassess plan as needed. Will reassess with new renovation menu for April. Complete. Implement changes depending on the analysis results. New option available and under investigation. Incomplete; not possible with this vendor. Research options and implement two rbst free, local cheeses per year. Purchasing new options available from Cabot. Complete. Reduce the amount of pork purchased. Complete. Purchase an additional 20%. Achieve this through investigating ground turkey and raw chicken breast. Evaluate processed foods containing beef. Updated to finding a source for stew beef. Reassess menu for variety and add north American sources of sustainable fish and seafood. Investigation of sources to continue. Research options and implement two rbst free (and local if possible) cheeses per year. Evaluate options available for local, sustainable pork products.

Food Category Status of Sustainable Purchases Additional Annual Cost Poultry All fajita and whole chickens - approximately 25 % Beef Fish and Seafood All beef tips, diced, cubes, and ground approximately 80 % All fish and Seafood is what we consider a green rating Comments $70,000 Met our goal $48,000 Met our goal None Met our goal Eggs No changes accomplished None Unsuccessful Cheese Pork Only 1 major product is currently in place insufficient options in the market Removed pork from the menu due to limited options $2500 Unsuccessful None Unsuccessful

Support for PAMTA Over 70 Facilities Nationwide Fletcher Allen Health Care, VT Porter Medical Center, VT Fairview Hospital, MA Covenant Health Systems, New England (14 facilities) Regis Care Center, NY Swedish Covenant, IL St. Luke s, MN Sacred Heart Hospital, WI Mercy Medical Center, Baltimore, MD Oregon Health and Science University, OR Catholic Healthcare West, AZ, NV, CA (40 facilities) St. Joseph Health System - Sonoma County, CA (7 facilities) Union Hospital, Maryland www. Protectantibiotics.org

Cost Versus Revenue $5,000,000 $4,500,000 $4,000,000 $3,500,000 $3,000,000 $2,500,000 $2,000,000 $1,500,000 $1,000,000 $500,000 $- 04 05 06 07 08 09 Total Volume Revenue Food Costs

Education

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The Center for Nutrition and Healthy Food Systems

The Pew Campaign on Human Health and Industrial Farming

The Pew Campaign on Human Health and Industrial Farming

The Pew Campaign on Human Health and Industrial Farming The independent Pew Commission on Industrial Farm Animal Production (PCIFAP) was formed to conduct a comprehensive, fact based and balanced examination of key aspects of the farm animal industry. Commissioners represented diverse backgrounds and perspectives and came from the fields of veterinary medicine, agriculture, public health, business, government, rural advocacy and animal welfare. In April, 2008 the Commission released the full report of findings with 24 recommendations in public health, the environment, animal welfare and community impact. Banning all non therapeutic antimicrobial use in food animal production was one of the top recommendations from the Commission.

The Pew Campaign on Human Health and Industrial Farming Commission definitions: Therapeutic: The use of antimicrobials in food animals with diagnosed microbial disease. Non therapeutic: Any use of antimicrobials in food animals in the absence of microbial disease; any use of the drug as an additive for growth promotion, feed efficiency, weight gain, routine disease prevention in the absence of documented exposure or other routine purpose. Prevention: The use of antimicrobials in healthy animals in advance of an expected exposure to an infectious agent or after such an exposure but before onset of laboratory confirmed clinical disease as determined by a licensed professional.

The Pew Campaign on Human Health and Industrial Farming The goal of the Pew Campaign on Human Health and Industrial Farming (HHIF) is to reduce antibiotic resistance in humans by phasing out the routine use of antibiotics in food animal production through legislative and/or regulatory action. The Preservation of Antibiotics for Medical Treatment Act (PAMTA, H.R. 1549/S. 619) was introduced in March, 2009. PAMTA would withdraw the routine use of seven classes of antibiotics vitally important to human health from food animal production unless animals or herds are sick with disease or unless drug companies can prove that their routine use does not harm human health.

The Pew Campaign on Human Health and Industrial Farming FDA Deputy Commissioner Joshua Sharfstein, M.D., House Energy & Commerce Sub Committee on Health, Hearing July 14, 2010. FDA concludes that the overall weight of evidence to date supports the conclusion that using medically important antimicrobial drugs for production purposes is not in the interest of protecting and promoting the public health. The FDA has since initiated two actions: FDA Draft Guidance The Judicious Use of Medically Important Antimicrobial Drugs in Food Producing Animals. The guidance should be stronger and go further to protect antibiotics. FDA Advance Notice of Proposed Rulemaking on the Veterinary Feed Directive. Could result in a weakening of the oversight that was set up to help prevent unnecessary drug use and further development of bacterial resistance to antibiotics.

The Pew Campaign on Human Health and Industrial Farming USDA Economic Research Service study, January 2009. A heavy reliance on antibiotics for growth promotion and for disease prevention may spawn antibiotic resistant strains of bacteria, with human health risks. Growth promoting antibiotics are more likely to be used on larger hog operations. Producers not reliant on growth promoting antibiotics utilize improved husbandry practices such as extensive testing and improved sanitary protocols to prevent disease and promote growth. USDA Deputy Administrator John Clifford, DVM, House Energy & Commerce Sub Committee on Health, Hearing July 14, 2010. USDA believes that it is likely that the use of antimicrobials in animal agriculture does lead to some cases of antimicrobial resistance among humans and in animals themselves, and we believe that we must use medically important antimicrobials judiciously. USDA Agriculture Secretary Tom Vilsack, September 15, 2010. I ve communicated to Rep. Slaughter, my support of the judicious use of antibiotics. The vast majority of producers do not abuse the use of antibiotics in livestock production. I told her you cannot ban this. It doesn t make sense. USDA s position is, and always has been, that antibiotics need to used judiciously and we believe they already are.

The Pew Campaign on Human Health and Industrial Farming Denmark. Recognizing the potential for a health crisis, in 1998 Denmark began restricting the non therapeutic use of antibiotics in cattle, broiler chickens and swine. Overall antibiotic use in swine dropped by more than 50 percent from 1992 to 2008. Swine production increased by nearly 50 percent during the same period. Adjustments made in husbandry practices allowing swine to be more productive Antibiotic resistance in humans has decreased after implementation of the ban.

The Pew Campaign on Human Health and Industrial Farming www.saveantibiotics.org Laura Rogers, Project Director lrogers@pewtrusts.org