Antibiotic Use in the Food Supply and Connection with

Antibiotic Resistance

by Jessica Moehling and Stephanie Send

February 11th, 2016

Outline Objectives

Mechanism Behind Antibiotic Resistance

History of Antibiotic Use in the Food Supply

History of Drug Resistance

Pros for the Ban of Antibiotics in the Food Supply

Cons Against the Ban of Antibiotics in the Food Supply

Conclusions and Recommendations

Discussion

Objectives

•  What are some of the proposed reasons we are seeing an increase in antibiotic resistance and multidrug resistance (MDR) in the United States?

•  What are the arguments as to why we should or should not restrict antibiotic use in farm animals?

•  How can we apply this information to our practice?

Time for a Poll!

History of Antibiotic Use in Food Supply •  In the 1950s, the concentration of food-producing animals began to increase

while the number of total farms decreased

•  Farms began keeping more animals closer together

•  Increased animal contact resulted in increased transmission of illnesses

•  Small subtherapeutic doses of procaine penicillin and tetracycline were given to prevent widespread illness

•  Farmers at the time realized antibiotics could enhance feed-to-weight ratio for food animals

Marshall and Levy. Clin Microbiol Rev. 2011

Increase in Number of Food Animals Over Time

Humane Society. Farm animal statistics: Slaughter totals. 2015; Dimitri et al. The 20th century transformation of U.S. agriculture and farm policy. 2005

Current Poultry Farm

Farm Relief. Poultry services. 2015

Antibiotics for Growth Promotion •  Average growth improvement estimated to be between 4-8%

•  Average feed utilization improvement estimated to be between 2-5%

•  Mechanism of growth promotion not fully understood

•  Nutrients protected against bacterial destruction

•  Improved absorption of nutrients due to thinning of intestinal barrier

•  Decreased production of toxins by intestinal bacteria

•  Reduction in the incidence of subclinical intestinal infections

Butaye et al. Clin Microbiol Rev. 2003; Dibner & Richards. Poult Sci. 2005

History of Drug Resistance

Hogberg et al. Trends Pharmacol Sci.. 2010

http://www.cdc.gov/foodsafety/challenges/from-farm-to-table

Pros •  Evidence of MDR bacteria present in animals, retail meat,

and humans

•  Evidence of animal to human transfer of MDR bacteria

•  Currently behind other countries which have already banned antibiotic use

•  Rise in MDR associated community outbreaks, negatively impacting healthcare costs and increasing MDR related hospitalizations and deaths

Use of Antibiotics in the United States •  Nearly 80% of total antibiotic use in the United States is on healthy farm

animals

•  Approximately 32 million tons of antibiotics sold for use in food animals

•  Estimated 2,049,442 illnesses and 23,000 deaths each year related to antibiotic resistance

•  Farmers are NOT required to report antibiotic usage or reasons for usage in farming

•  The only FDA mandated antibiotic ban was in 2005, when fluoroquinolones were withdrawn from the agricultural market due to concerns for human antibiotic resistance CDC. Antibiotic Resistance Threats in the United States. 2013.

Antibiotic Resistance in Retail Meat

FDA. NARMS Retail Meat Report. 2011.

•  National Antimicrobial Resistance Monitoring System (NARMS) Retail Meat Report

•  44.9% of retail chicken and 50.3% of retail ground turkey with Salmonella found to be multidrug resistant (MDR)

•  Of the meat samples tested, 55.7% were positive for E. coli

•  37.5% of chicken and 64.4% of ground turkey were MDR

•  Among ground turkey, ampicillin resistance increased from 31.3% in 2002 to 51.6% 2011 (p<0.0001)

•  While fluoroquinolone resistance has decreased since 2005 (29.1%-18.1%,), tetracycline resistance has increased in both C. jejuni (36.3%-48.4%) and C. coli (39.2%-49.1%) (p<0.001)

FDA. NARMS Retail Meat Report. 2011.

FDA. NARMS Retail Meat Report. 2011.

Millman et al. F1000Res. 2013.

What Other Countries are Doing •  In the 1960’s, the Swann Report was published in the UK, which identified that

MDR bacteria was on the rise due to use of growth promoting antibiotics •  Between the years of 1995 and 1999, several growth promoting antibiotics

were banned in the European Union •  Denmark is the considered the “gold standard” for tracking changes in antibiotic

use and resistance patterns •  Unfortunately, use of therapeutic doses of antibiotics increased due to higher incidence of animal

disease; farming practices have since been adjusted to decrease disease and antibiotic use •  Mixed data relating to changes in antimicrobial resistance post ban •  Post avoparcin ban (1995), animal VRE reduced from 73-80% to 5-6% •  Human VRE colonizations also declined in Germany (13-4%) and Belgium (5.7-0.7%)

Phillips. Int J Antimicrob Agents. 2007. Levy. Clin. Microbiol. Rev. 2011.

Prevalence of MDR Bacteria in Humans and Animals

Doyle. Foodborne Pathogens and Disease. 2015.

Animal to Human Transfer of Antibiotic Resistance

Levy. Clin. Microbiol. Rev. 2011.

Animal to Human Transfer of Antibiotic Resistance

Levy. Clin. Microbiol. Rev. 2011.

Drug Resistant Antibacterial Threats ●  Carbapenem-resistant Enterobacteriaceae (CRE or KPC) ●  MDR Campylobacter ●  Vancomycin resistant Enterococcus (VRE) ●  DR Non-typhoidal Salmonellae (most common) ●  DR Salmonella Typhi ●  DR Shigella ●  Methicillin-resistant Staphylococcus aureus (MRSA) ●  DR Streptococcus pneumonia ●  DR tuberculosis ●  Vancomycin-resistant Staphylococcus aureus (VRSA) ●  Erythromycin-resistant Streptococcus Group A ●  Clindamycin-resistant Streptococcus Group B

CDC. Antibiotic Resistance Threats in the United States. 2013.

Foodborne E. Coli and Urinary Tract Infections •  Urinary tract infections (UTIs) are the most common bacterial infection in the

US •  Most only affect the bladder, but some travel and infect the kidney (250,000 cases each year)

•  These infections can get into the bloodstream and cause urosepsis, which can occur due to antibiotic resistant bacteria, such as E. coli.

•  Manges (2007) •  Case-control study conducted at University of California Berkeley wanted to determine dietary

patterns of 99 women with UTIs

•  Block 1998 FFQ used

•  Classified as MDR or non MDR UTI caused by E. coli

Nordstrom et al. Front Microbiol. 2013 Manges et al. Foodborne Pathogens and Disease. 2007.

Results: Manges et at (2007)

Manges et al. Foodborne Pathogens and Disease. 2007.

Klebsiella pneumoniae and Urinary Tract Infections •  K. pneumoniae was isolated from turkey, chicken, and pork from grocery

stores in Flagstaff, AZ as well as from blood and urine specimens of patients with resistant UTIs at Flagstaff Medical Center in 2011-2012

•  Whole genome sequencing was randomly completed on 82 of the K. pneumoniae isolates (38 clinical and 44 meat-source) and bacteria was classified as MDR if resistant to >2 antibiotics

•  Results indicated that 22% of isolates were MDR (32% of meat and 8% of clinical)

•  5 of the clinical isolates (13%) were closely related to meat isolates, 4 of which were resistant to ampicillin Davis et al. Clin Infect Dis. 2015.

Methicillin-Resistant Staphylococcus aureus (MRSA) •  MRSA is a serious bacterial infection that costs $478-$2200 million dollars

annually

•  MRSA has recently been found to be of community origin rather than hospital-acquired

•  In Europe, MRSA outbreaks (specifically subtype ST398) have been linked to high-density livestock production

•  In 2012, a yearlong study was done in rural Pennsylvania to determine the association between MRSA infections and relative location of high density livestock production areas

Casey et al. Environ Health Perspect. 2014..

Casey et al. Environ Health Perspect. 2014..

Casey et al. Environ Health Perspect. 2014..

Limitations of the Literature •  Majority of research conducted outside the United States

•  Literature contradictory and often biased

•  Difficult to correlate a specific meat supply to a specific infection in a particular human

•  Small sample sizes

•  Not generalizable due to differences in geographical locations

•  Infinite number of bacteria strains and antibiotics, making it difficult to condense the literature and simplify into overall message

Time for a Poll!

Cons •  Decreased growth ability of farm animals

•  Inadequate evidence that restricting antibiotic use will decrease drug resistance

•  Focus should be on food safety

•  Control antibiotic use in humans

Decreased Growth Ability of Food Animals •  Denmark

•  Feed conversion of broilers increased from 1995-1999, then plateaued

•  Average daily gain in pigs declined from 1995-2001

•  United States

•  From 1955-1995 the average broiler weight has increased by 50%

•  Time needed for broilers to reach market weight and and amount of feed to produce one pound of broiler meat has decreased by approximately 35%

Dibner & Richards. Poult Sci. 2005; Graham et al. Public Health Rep. 2007

Engester et al. J Appl Poult Res. 2002; Graham et al. Public Health Rep. 2007. MacDonald and Wang. Appl Econ Perspect Policy. 2011; Teillant and Laxminarayan. Choices. 2015.

Inadequate evidence that restricting antibiotic use will decrease drug resistance •  Study by Khachatryan et al. (2006)

•  27 neonatal calves were separated into three groups

•  Dietary supplement

•  Dietary supplement + oxytetracycline

•  No dietary supplement (control)

•  Fecal samples from each calf were collected once a week for 3 months

•  ANOVA was used to determine the difference in antibiotic resistance between the three groups

Khachatryan et al. Appl Enviorn Microbiol. 2006

Khachatryan et al. (2006): Results

Khachatryan et al. Appl Enviorn Microbiol. 2006

Focus on Food Safety •  1 in 6 Americans become sick from contaminated food or beverages each year

•  Approximately 3000 Americans each year die from foodborne illnesses

•  $365 million in direct medical costs annually from Salmonella-related hospitalizations and deaths alone

•  Reducing foodborne illness by 10% would result in the reduction of 5 million incidences of foodborne illnesses

Centers for Disease Control and Prevention. Food safety. 2015

De Jong et al (2008) •  Inoculated raw chicken fillets with mixture of Campylobacter jejuni, and L. casei

strains

•  Prepared curry-chicken salad in a consumer kitchen •  Recipe and set of directions was followed to simulate a “best case scenario”

•  Modifications to the set of directions were made to simulate the potential cross-contamination events that occur in a consumer kitchen (hand washing, cutlery, cutting board)

•  Best case scenarios resulted in undetectable levels of bacteria in the salads •  3 methods of average consumer handwashing was not enough to prevent cross-contamination

•  Washing the cutting board used to prepare raw meat under warm water and soap was not enough to prevent cross-contamination though was effective for preventing cross-contamination from cutlery

De Jong et al. J Appl Microbiol. 2008

Byrd-Bredbenner et al (2013)

Byrd-Bredbenner et al. Int J Environ Res Public Health. 2013

Control Antibiotic Use in Humans •  Antibiotic resistance can be selected for when:

•  Antibiotics are prescribed for viral infections

•  Antibiotics are prescribed for bacterial infections before species and sensitivity is assessed

•  Patients do not finish their full course of antibiotics

•  Emphasis should be placed on technology that allows for rapid determination of species and sensitivity

•  Patients should be educated on importance of finishing antibiotic course

Doyle. Foodborne Pathog Dis. 2008

Centers for Disease Control and Prevention. Get smart: Know when antibiotics work. 2015

Time for a Poll!

Actions •  In 2013, the CDC released four core actions to aid in decreasing

antibiotic resistance: •  Preventing infections

•  Tracking of antibiotic resistant infections

•  Antibiotic stewardship and improving antibiotic prescribing

•  Developing new drugs and diagnostic testing

•  National Antimicrobial Resistance Monitoring System (NARMS)

•  In 2013, FDA implemented a voluntary plan to phase out growth promoting and feed efficiency antibiotics

•  Only 40% of dairy farmers follow the USDA voluntary quality assurance programs

CDC. Antibiotic Resistance Threats in the United States. 2013.

Conclusions and Recommendations •  Educate patients/public on importance of food safety practices and how to

apply them at home

•  When shopping for antibiotic-free products, look for key terms such as:

•  Animal Welfare Approved

•  Certified Humane

•  Gap Steps 1-5+ (Whole Foods)

•  Organic- interpret with caution

•  No Antibiotics Used/Raised without Antibiotics

Antibiotic Use in Chain Restaurants

ConsumerReports.org/superbugs

Antibiotic Use in Meat Producers

ConsumerReports.org/superbugs

Discussion Questions 1. What role does the RD play with the issue of antibiotic resistance?

2. Is it within our scope of practice to advocate for bans against antibiotics?

3. Would any of this information change your recommendations to patients, and if so, how?

4. Do you feel that your nutrition education provided you with enough, if any, information on this topic?

5. How confident do you feel that our patients as well as ourselves can have an impact on minimizing antibiotic resistance?

6. What do you believe is the biggest take home message from this presentation?

References 1. Farm animal statistics: Slaughter totals : The humane society of the united states http://www.humanesociety.org/news/resources/research/stats_slaughter_totals.html. Accessed 2/7/2016, 2016. 2. CDC and food safety | food safety | CDC http://www.cdc.gov/foodsafety/cdc-and-food-safety.html. Accessed 2/6/2016, 2016. 3. Get smart about antibiotics | measuring outpatient prescribing | CDC http://www.cdc.gov/getsmart/community/programs-measurement/measuring-antibiotic-prescribing.html. Accessed 2/9/2016, 2016. 4. Butaye P, Devriese LA, Haesebrouck F. Antimicrobial growth promoters used in animal feed: Effects of less well known antibiotics on gram-positive bacteria. Clin Microbiol Rev. 2003;16(2):175-188. 5. Byrd-Bredbenner C, Berning J, Martin-Biggers J, Quick V. Food safety in home kitchens: A synthesis of the literature. Int J Environ Res Public Health. 2013;10(9):4060-4085. 6. Casey JA, Shopsin B, Cosgrove SE, et al. High-density livestock production and molecularly characterized MRSA infections in pennsylvania. Environ Health Perspect. 2014;122(5):464-470. 7. CDC. Antibiotic resistance threats in the united states. 2013. 8. Center for Disease Dynamics, Economics & Policy (CDDEP). Resistance map. http://resistancemap.cddep.org/resmap/resistance. Accessed 2/5/2016, 2016. 9. Consumer Reports. Making the world safe from superbugs. 2013. 10. Davis GS, Waits K, Nordstrom L, et al. Intermingled klebsiella pneumoniae populations between retail meats and human urinary tract infections. Clin Infect Dis. 2015;61(6):892-899. 11. De Jong AEI, Verhoeff-Bakkenes L, Nauta MJ, De Jonge R. Cross-contamination in the kitchen: Effect of hygiene measures. J Appl Microbiol. 2008;105(2):615-624. 12. Dibner JJ, Richards JD. Antibiotic growth promoters in agriculture: History and mode of action. Poult Sci. 2005;84(4):634-643. 13. Dimitri C, Effland A, Conklin N. The 20th century transformation of U.S. agriculture and farm policy. http://www.ers.usda.gov/media/259572/eib3_1_.pdf. Accessed 2/7/2016, 2016. 14. Doyle ME. Multidrug-resistant pathogens in the food supply. Foodborne Pathog Dis. 2015;12(4):261-279. 15. Engster HM, Marvil D, Stewart-Brown B. The effect of withdrawing growth promoting antibiotics from broiler chickens: A long-term commercial industry study. J Appl Poult Res. 2002;11(4):431-436.

References Cont. 16. FDA. National antimicrobial resistance monitoring program retail meat report. 2011. 17. Graham JP, Boland JJ, Silbergeld E. Growth promoting antibiotics in food animal production: An economic analysis. Public Health Rep. 2007;122(1):79-87. 18. Högberg LD, Heddini A, Cars O. The global need for effective antibiotics: Challenges and recent advances. Trends Pharmacol Sci. 2010;31(11):509-515. 19. Khachatryan AR, Besser TE, Hancock DD, Call DR. Use of a non medicated dietary supplement correlates with increased prevalence of streptomycin-sulfa-tetracycline-resistant escherichia coli on a dairy farm. Appl Environ Microbiol. 2006;72(7):4583-4588. 20. MacDonald JM, Wang S-. Foregoing sub-therapeutic antibiotics: The impact on broiler grow-out operations. Appl Econ Perspect Policy. 2011;33(1):79-98. 21. Manges AR, Smith SP, Lau BJ, et al. Retail meat consumption and the acquisition of antimicrobial resistant escherichia coli causing urinary tract infections: A case-control study. Foodborne Pathog Dis. 2007;4(4):419-431. 22. Marshall BM, Levy SB. Food animals and antimicrobials: Impacts on human health. Clin Microbiol Rev. 2011;24(4):718-733. 23. Millman JM, Waits K, Grande H, et al. Prevalence of antibiotic-resistant E. coli in retail chicken: Comparing conventional, organic, kosher, and raised without antibiotics. F1000Res. 2013;2:155-155.v2. eCollection 2013. 24. Nordstrom L, Liu CM, Price LB. Foodborne urinary tract infections: A new paradigm for antimicrobial-resistant foodborne illness. Front Microbiol. 2013;4:29. 25. Phillips I. Withdrawal of growth-promoting antibiotics in europe and its effects in relation to human health. Int J Antimicrob Agents. 2007;30(2):101-107. 26. Teillant A, Laxminarayan R. Economics of antibiotic use in U.S. swine and poultry production. Choices. 2015;30(1). Accessed 2/4/2016.