AMU/AMR Policy for animals in Korea Jaehong CHANG, DVM, MS

AMU/AMR Policy for animals in Korea Jaehong CHANG, DVM, MS Deputy Director of Animal Health Management Division, Ministry of Agriculture, Food and Rural Affairs, Republic of Korea

Contents Background Consequence of phase-out feed additives - Antimicrobial consumption - Antimicrobial resistance - Animal and Human health National action plan on AMR

Background

Livestock number in Korea Species Year Numbers (thousands) 2005 2007 2009 2011 2013 2014 Cattle 2,316 2,654 3,080 3,354 3,342 3,190 Chickens 109,628 119,365 138,768 149,511 151,337 156,410 Ducks 8,389 10,513 12,733 15,053 10,899 7,539 Goats 523 372 249 247 242 243 Horses 20 25 29 30 29 29 Pigs 8,962 9,606 9,585 8,171 9,912 10,090 Sheep 1 2 3 3 3 0 Production scale (2013, Korea/global): cattle (0.22%), pigs (1.01%), chicken (0.7%), and duck (0.82%)

Major regulations for antimicrobial use in livestock Pharmaceutical Affairs Act (Ministry of Health and Welfare, Ministry of Food and Drug Safety) Regulation on animal medicines and others (Minister of Agriculture, Food and Rural affairs) Regulatory Guidelines on use of Animal Medicines for Formula Feed (MAFRA) Regulatory Guidelines of designation for Prescription Animal Medicines (MAFRA) Guidelines on safe use of Animal Medicines (QIA under MAFRA)

Press release of AMR contamination in foods Heavy contamination of Multi-Drug Resistant bacteria in 18 major food items including beef, pork, and fisheries - 100% of Salmonella isolates showed resistance to one more antimicrobial - Furthermore, 63% of Salmonella isolates showed resistance to four more antimicrobials Percentage % 100 80 60 40 20 0 Coliform Group Salmonella Listeria Staphylococcus Vibrio Over 1 Antibiotics Over 4 Antibiotics Press Release : Korea Consumer Protection Board in 2002

Press release of heavy use in animals and AMR contamination in animal products (2002-2003) (2006. CBS)

Early warnings and actions 1969 Swann Committee recommends restrictions on antimicrobials in animal feed 1997 WHO scientific meeting concludes that it is essential to replace growth promoting anti microbials 1998 EU bans four antimcirobials in animal feed as precautionary measure. 1999 2000 EU Scientific Steering Committee recommends phase-out of antimicrobials that may b e used in human/animal therapy WHO recommends ban on antimicrobials as growth promoters if used in h uman therapy and in absence of risk-based evaluation 2006 Total ban on antibiotics as growth promoters in EU (Source : Late lessons from early warnings: the precautionary principle 1896 2000 : Antimicrobials as growth promoters: resistance to common sense, LE Edqvist&KB Pedersen, 93-100)

Launch the National Antimicrobial Resistance Management Program - Relevant government ministry & academia Non-human sector Human sector Ministry of Agriculture, Food and Rural Affairs Develop AR Management System in Livestock Farming 20 Medical Centers in Korea Univ. Hospitals Develop AR Management System in Clinical Patient Ministry of Marine Affairs & Fisheries (NFRDI) Develop AR Management System in Aquaculture KFDA Food Microbiology Division Monitoring Antimicrobial Resistant Foodborne Bacteria Dong Guk University Monitoring of Antibiotic Residue in Foods Ministry of Finance and Economy Korea Consumer Protection Board Surveillance of AR in Environment Ministry of Food & Drug Safety Overall Management Networking Information Refining Advisory Committee Public Campaign International Activities Monitoring AR in Foods Ministry of Science & Technology Culture Collection of Antimicrobial Resistant Microbes Educate National Standard AR Inspection Method Ministry of Health & Welfare(KCDC) Monitoring of AR in Community, Prevalence Study of Antimicrobial Resistance from Diarrhea Patients Research Institute of Health & Environment Prevalence Study of Antimicrobial Resistance from Diarrhea Patients Chonnam National/Kosin University College of Medicine Monitoring Antimicrobial Resistance in public Society/ Construction of Roadmap for Overcoming AR in Medical Area Ministry of Health & Welfare National Health Insurance Corporation Surveillance of Clinical Antibiotic Usage (modified Dr. Woo s slide )

Main activities of national project on AMR (2003 2012) Organizing an Advisory Committee Board of National Antimicrobial Resistance Experts (35) Developing monitoring program on antimicrobial consumption and resistance in Clinical, Livestock & Fishery sectors Implementation of risk management measures on antimicrobial resistance in Livestock and Fishery sectors Investigating Antimicrobial Resistance in Foods Establishing the National Surveillance Network Education and training for Prudent Use of Antibiotics in both humans and animals

Main barriers to combat AMR(1) Opposition of animal production association & Farmers - Reasons: animal production cost, usage of therapeutic antimicrobials, disease incidence, birth to approximate slaughter date (productivity ) Increase support for the environment that reduces the need for antibiotics - Financial support : $700,000( 09) $16,200,000( 14) Encouraging the animal hygiene and livestock raising practices - Certified HACCP farms : 379( 08) 6,675( 15)

Main barriers(2) Portion of usage of antimicrobials which added to feed, water, and injected in animals at individual farms was increasing 44.6%( 01) 45.7%( 03) 49.9%( 05) 54.9%( 07) 67.0%( 09) 78%( 11) No veterinary oversight system (ex. Vet. Drugs Prescription System) Implementation of veterinary prescription on animal drug in Aug. 2013 Vet. prescription is being implemented in three stage during 2013-2018 - 1 st stage (Aug. 2013): macrolides, 3 rd &4 th cephalosporins, fluoroquinolones, tetracyclines - 2 nd (2016) : under discussion (will be included critically important antimicrobials) - 3 rd (2018) : scheduled

Actions of AMR management in Livestock 1. Strengthening the National Monitoring Program - Korean Veterinary Antimicrobial Resistance Monitoring System 2. Implementation of regulation on antimicrobial use - Regulatory Guidelines on use of Animal Medicines for Formula Feed : Antimicrobial resistance committee decided the ban of antibiotic addition in animal feed according to international guidelines * Antimicrobial resistance committee comprises of academics, government officials, and producers' association Regulatory Guidelines of designation for Prescription Animal Medicines - Guidelines on safe use of Animal Medicines

KVARMS (Korean 항생제 Veterinary 판매 Antimicrobial 및내성 Resistance 모니터링 System) 체계 Distribution Consumption Korean Animal Health Product Association data Annual report Animals Carcasses 14 Provincial Vet. Service 14 Pro. Vet. Service Isolates Isolates Animal & Plant Quarantine Agency data Retail meats Ministry of Food & Drug Safety data Imported meats Ministry of Food & Drug Safety data (Homepage)

KVARMS Korean Animal Health Product Association Consumption of Antimicrobials Resistance in animal pathogens (Pathogenic E. coli, Salmonella, P. multocida, A. pleuropleumoniae etc) Resistance in indicator bacteria (E. coli, E. faecium/e.faecalis) Diseased animals Resistance in food pathogens (Salmonella, S. aureus, C. jejuni/c. coli) Healthy animals Raw meat

Banned antibiotics in feeds 1997-2003 : avoparcin, spiramycin, olaquniodox, spectinomycin, flubendazol etc 2005. 05 (53 25) : Oxytetracycline HCl, Erythromycin, Sulfadimethoxine etc 2009.01 (25 18) : Oxytetracycline, Chlortetracycline, Bacitracin zinc, Colistin sulfate, Lincomycin hydrochloride, Neomycin sulfate, Penicillin 2011. 07 (18 9 inophores) : apramycin, avilamycin, bambermycin, bacitracin methylene disalicylate, enramycin, tiamulin, tylosin, virginiamycin, sulfathiazole * 9 inophores : Narasin, Diclazuril, Lasalocid, Madurmycin, Monensin, Salinomycin, Semduramycin, Clopidol, Fenbenzazole

Consequence of Banning of antibiotics in animal feed

Tousands of animals Millions of broilers Consumption of antimicrobials Consumption (tons) 2,000 1,500 1,000 28 AGP ban( 05.5) Feed additives(tons) 7 AGP ban( 09.1) 9 AGP ban( 11.7) : phase out all antibiotics Vet. Prescription( 13.8 : 20 antibiotics 500 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 (Source: Korea Animal Health Products Association) No. of livestock(1,000 head) 15000 10000 5000 0 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Press Release : Korea in 2002 (Source: Statistics Korea) Cattle Pigs Poultry 200 150 100 50 0

Year antimicro bials (ton) Antimicrobial consumption /meat production Cattle Swine Poultry meat product (kton) Antimicro bials (ton)/me at product (kton) antimicro bials (ton) meat product (kton) Antimicro bials (ton)/me at product (kton) antimicro bials (ton) meat product (kton) Antimicro bials (ton)/me at product (kton) 2003 108 188 0.57 818 1,149 0.71 348 429 0.81 2004 97 186 0.52 771 960 0.80 282 432 0.65 2005 112 195 0.57 831 899 0.92 335 536 0.63 2006 119 200 0.60 836 1,000 0.84 282 563 0.50 2007 121 219 0.55 874 1,043 0.84 280 570 0.49 2008 99 246 0.40 662 1,056 0.63 256 565 0.45 2009 63 283 0.22 551 1,062 0.52 206 613 0.34 2010 57 247 0.23 582 1,110 0.52 204 653 0.31 2011 58 280 0.21 459 837 0.55 200 686 0.29 2012 65 300 0.22 449 982 0.46 228 695 0.33 2013 56 336 0.17 312 1,007 0.31 122 685 0.18 Source : Meat production : FAOSTAT( http://faostat.fao.org/?alias=faostatclassic Antimicrobial usage: Korea Animal Health Product Association

Antimicrobial classes Antimicrobial consumption Amount of antimicrobial used (AI, ton) 2003 2005 2007 2009 2011 2013 2015 Tetracyclines 724 723 624 288 308 269 237 Sulfonamides 181 200 183 92 100 75 99 Penicillins 130 229 267 151 155 187 223 Aminoglycosides 79 72 94 51 46 37 48 Macrolides 48 55 75 88 60 41 66 Quinolones 33 53 57 37 51 50 49 Ionophores 62 97 88 75 78 55 43 Polypeptides 25 34 39 97 57 10 12 Phenicols 10 25 34 55 59 65 93 Pleuromutilins 15 18 21 35 22 14 18 Quinoxalines 5 16 13 5 - - - Lincosamides 10 14 16 6 8 8 9 Cephalosporins 2 2 2 3 6 8 10 Streptogramins 4 5 5 8 3 1 0.2 Orthosomycins 5 4 5 6 1 0 0 Glycolipid 5 3 2 2 1 0 0 Nitrofurans 63 - - - - - - Others 38 2 0 0 1 1 0 Total 1,439 1,553 1,527 998 956 820 909 (Source: Korea Animal Health Products Association)

% resistant isolates % resistant isolates Trends of antimicrobial resistance of E. coli from healthy animals 100 % Cattle Pigs tetracycline Poultry ciprofloxacin 50 % 0 % ceftiofur ceftiofur 121 125 184 231 347 282 209 299 206 239 116 185 221 231 277 199 294 218 169 106 97 155 141 200 187 192 189 2007 2008 2009 2010 2011 2012 2013 2014 2015 2007 2008 2009 2010 2011 2012 2013 2014 2015 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year and number of isolates 100 % Cattle carcasses Pig carcasses Chicken carcasses 50 % 0 % 57 51 51 136 190 111 96 159 125 62 61 48 124 153 134 96 160 111 96 100 76 107 121 163 107 140 127 2007 2008 2009 2010 2011 2012 2013 2014 2015 2007 2008 2009 2010 2011 2012 2013 2014 2015 2007 2008 2009 2010 2011 2012 2013 2014 2015 Year and number of isolates Ampicillin Gentamicin Streptomycin Ceftiofur Ciprofloxacin Tetracycline Trimethoprim/Sulfamethoxazole Chloramphenicol (Source: Korean Veterinary Antimicrobial Resistance System) Resistance to tetracycline, streptomycin, trimethoprim/sulfamethoxazole has been decreasing in pigs (carcasses) and chickens (carcasses) Resistant rate against ciprofloxacin and ceftiofur has been increasing in chicken and pigs

Usage of TC(ton) Resistance of TC(%) Comparison of consumption and resistance Tetracycline 450 400 350 300 250 200 150 100 50 97.8 75.0 75.0 91.5 85.2 80.0 94.5 87.0 61.8 64.0 46.3 36.7 82.8 47.2 19.0 70.8 30.2 23.0 77.6 15.2 15.0 62.9 63.9 26.0 19.4 21.6 21.1 100 80 60 40 20 0 '07 '08 '09 '10 '11 '12 '13 14 15 0 TC amount(cattle) TC amount (pigs) TC amount (chicken) Resistance of E. faecium from cattle Resistance of E. faecium from pigs Resistance of E. faecium from chicken (Source: KAKPA, KVARMS)

Consequence of banning of antibiotics in animal feed in Korea 1. Usage of antimicrobials - Total amount of antimicrobials decreased by about 40% from 2005 to 2015 - Usage of antibiotics for feed additives (tetracyclines,sulfonamides) were decreased, wherase therapeutic antimibiotics(3 rd generation cephalosporins, fluoroquinolone, phenicols) were increased 2. Antimicrobial resistance - Resistance to tetracycline, aminoglycosides, and sulfonamides decreased, while resistance to therapeutic antimicrobilas maintained the same or increased 3. Animal health - No significant increase of bacterial disease in animals and mortality rate in pigs

National Action Plan on Antimicrobial Resistance (2016-2020)

National Action Plan on Antimicrobial Resistance Vision Decrease the misuse or abuse of antibiotics, use them appropriately, and prevent antibiotic-resistant bacteria transmission Protect citizens from the harm of antimicrobial resistance Goals In humans In non-humans Reduce the antibiotic use by 20% Double the number of antibiotics needed to be Reduce the antibiotic prescription for acute prescribed by veterinarian upper respiratory infection by 50% Reduce fluoroquinolone-resistant E. coli in Reduce the antibiotic prescription for respiratory poultry by 10% diseases by 20% Reduce the prevalence of methicillin- resistant S. aureus by 20%

Six strategies to achieve the vision 1. Use antibiotics appropriately 2. Prevent the spread of antibiotic-resistant bacteria 3. Strengthen the surveillance system 4. Raise awareness 5. Enhance infrastructure and R&D support 6. Accelerate international collaboration

Detailed action plans in non-humans 1. Use antibiotics appropriately Appropriately use of antibiotics for agriculture, livestock, and fisheries : implementation of prescription, sales management, reevaluation of drugs, developed guidelines 2. Prevent the spread of antibiotic-resistant bacteria Prevent the spread of AMR in agriculture, livestock, and fisheries : Improvement of breeding environment, lntegrated Information System for Infection Prevention in Fisheries

Detailed action plans in non-humans 3. Strengthen the Surveillance System Frame for surveillance : monitoring on duck and pet will be added Laboratories : testing capacities for antimicrobial-resistant pathogens will be enhanced, and a national standard laboratory will be established. Residue Test : the scope of the national residue program (NRP) on agriculture, livestock, and fisheries products will be expanded 4. Improve Awareness Raise awareness of the general public Enhance the understanding of antibiotic users (professionals) Perform periodical surveys on public understanding on antibiotics

Detailed action plans in non-humans 5. Enhance infrastructure and R&D support Interministerial framework for actions Web-based portal system for antibiotics Increase strategic investment in R&D for tackling AMR - One health concept monitoring on antimicrobial use and resistance - Rapid diagnostic test, new antibiotics and alternative therapeutics 6. Accelerate international collaboration Enhance global partnership to combat AMR Seek funding opportunities globally

Thank you for your attention