Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic

Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens Michael Doyle

Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens ● ● Major zoonotic foodborne bacterial pathogens ▲ Dissemination to foods ▲ Prevalence in livestock and poultry ▲ Prevalence in foods of animal origin Trends in foodborne illnesses caused by zoonotic pathogens Foodborne outbreak and sporadic case data Public health issues associated with antibioticresistant foodborne pathogens

Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens ● ● ● Types of antibiotic-resistant foodborne pathogens in USA Emergence and incidence of antibiotic-resistant foodborne pathogen infections ▲ Risk factors associated with acquiring antibiotic resistant foodborne microbial infections Trends in prevalence of antibiotic-resistant zoonotic foodborne pathogens in animals, foods and human illness

Major Bacteriological Causes of Enteric Foodborne Illness in USA ● Campylobacter jejuni - estimated 2. 4 million cases/yr ● Salmonella sp. - estimated 1. 4 million cases/yr ● E. coli O 157: H 7 - estimated 73, 000 cases/yr P. Mead et al. Emerging Infect. Dis. 5: 607 -625 (1999)

Reservoirs of Enteric Foodborne Pathogens ● Carried in intestinal tract of wild and domestic animals (including cattle, poultry, and swine) and/or symptomatic and occasionally asymptomatic people ▲ Includes Salmonella, Campylobacter, enterohemorrhagic E. coli O 157: H 7 (principally cattle)

Primary Sources of Enteric Foodborne Pathogens that Contaminate Foods ● Animal manure ● Human feces

Transmission of Enteric Foodborne Pathogens to Foods ● Direct or indirect contact with animal or human feces ▲ Fecal matter can contaminate foods through: ♦ Use as a soil fertilizer in fields ♦ Polluted irrigation or processing water ♦ Defecation by animals in vicinity of produce fields or processing areas ♦ Presence on contact surfaces of food handling equipment ♦ Transmission by insects such as flies ♦ Human carriers with poor personal hygiene harvesting or handling foods

The Manure Glut: A Growing Environmental Threat ● Five tons of animal manure is produced annually nationwide for every person living in the United States ▲ The amount of animal manure is 130 times greater than the amount of human waste produced ▲ Cattle, hogs, chickens and turkey produced an estimated 1. 36 billion tons of manure in 1997 Democratic Staff of U. S. Senate Agriculture Committee (1998) “Animal Waste Pollution in America: An Emerging National Problem”

The U. S. Manure Glut (1997 estimates) Animal Cattle Hogs Chickens Turkeys TOTAL Solid Waste (Tons/yr) 1, 229, 190, 000 116, 652, 300 14, 394, 000 5, 425, 000 1. 36 billion

Percentage of Great Britain Livestock Manures Contaminated with Zoonotic Microbes Cattle Pathogen E. coli O 157: H 7 Salmonella Campylobacter Swine Fresha Storedb Poultry Sheep Fresh Stored 13. 2 9. 1 11. 9 15. 5 NDc ND 20. 8 22. 2 7. 7 10. 0 7. 9 5. 2 17. 9 11. 5 8. 3 11. 1 12. 8 9. 8 13. 5 10. 3 19. 4 7. 7 20. 8 11. 1 Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a M. L. Hutchison et al. Lett. Appl. Microbiol. 39: 207 -214 (2004)

Cell Numbers of Zoonotic Pathogens in British Livestock Manures Cell No. (CFU/g) of pathogen Cattle Swine Poultry Sheep Pathogen E. coli O 157 Fresha Storedb Fresh Stored Geo Mean Max Salmonella Geo Mean 1 X 103 3 X 108 3 X 102 8 X 104 4 X 103 8 X 105 1 X 103 2 X 104 NDc ND ND ND 8 X 102 5 X 104 3 X 102 5 X 103 2 X 103 3 X 103 6 X 102 2 X 102 4 X 103 7 X 102 6 X 103 Max Campylobacter 6 X 105 7 X 106 8 X 104 2 X 103 2 X 104 8 X 103 2 X 103 6 X 103 3 X 102 2 X 105 5 X 102 2 X 105 3 X 102 2 X 104 2 X 103 1 X 105 3 X 102 3 X 104 6 X 102 9 X 102 4 X 102 2 X 103 1 X 102 Geo Mean Max Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a M. L. Hutchison et al. Lett. Appl. Microbiol. 39: 207 -214 (2004)

Factors Associated with Presence of Salmonella in Cattle on Conventional and Organic Dairy Farms ● ● Studied dairy cattle for 1 yr (2000 - 2001) on 129 conventional and organic farms in MN, WI, MI and NY Factors associated with Salmonella fecal shedding by cattle: ▲ Farms with ≥ 100 cows more likely Salmonella-pos than smaller farms (OR = 2. 6; 95% CI, 1. 4 - 4. 6) ▲ Cows designated sick by farm personnel (OR = 2. 5; 95% CI, 1. 7 - 3. 7) ▲ Cows within 14 days of calving (OR = 1. 8; 95% CI, 1. 1 - 2. 8) ▲ Cows due for culling within 14 days (OR = 1. 9; 95% CI, 1. 0 3. 4) ▲ Midwestern states were more likely to have Salmonellapositive samples than NY ▲ Highest Salmonella shedding in summer, then fall, spring and winter C. P. Fossler et al. Prev. Vet. Med. 67: 39 -53 (2005)

Factors Associated with Presence of Salmonella in Cattle on Conventional and Organic Dairy Farms ● Environmental samples more likely to be Salmonella-positive: ▲ Samples from pens of sick cattle (OR = 7. 4; 95% CI, 3. 4 15. 8) ▲ Manure storage areas (OR = 6. 4; 95% CI, 3. 5 - 11. 7) ▲ Maternity pens (OR = 4. 2; 95% CI, 2. 2 - 8. 1) ▲ Haircoats of cattle to be culled (OR = 3. 9; 95% CI, 2. 2 - 2. 7) ▲ Milk filters (OR = 3. 3; 95% CI, 1. 4 - 5. 7) ▲ Cow waterers (OR = 2. 8; 95% CI, 1. 4 - 5. 7) ▲ Calf pens (OR = 2. 7; 95% CI, 1. 3 - 5. 3) ▲ Bird droppings from cow housing (OR = 2. 4; 95%, CI 1. 3 4. 4) C. P. Fossler et al. Prev. Vet. Med. 67: 39 -53 (2005)

Prevalence of Salmonella in Meat and Poultry Determined by USDAFSIS Pathogen Reduction/HACCP Verification Testing Program Calendar Year Broiler Carcasses Ground Chicken Ground Turkey Steer & Heifer Carcasses Bull & Cow Carcasses Ground Beef Hog Carcasses (% Positive) Baseline (Pre-1998) 20 44. 6 49. 9 1. 0 2. 7 7. 5 8. 7 1998 10. 8 4. 2 36. 5 0 1. 1 6. 4 5. 8 1999 11. 4 16. 2 31. 6 0. 3 2. 2 4. 3 9. 8 2000 9. 1 13. 8 25. 7 0. 4 2. 2 3. 3 6. 2 2001 11. 9 19. 5 26. 2 0. 6 2. 4 2. 8 3. 8 2002 11. 5 29. 1 17. 9 0. 3 1. 7 2. 6 3. 2 2003 12. 8 35. 5 25. 4 0. 4 1. 5 1. 7 2. 5 2004 13. 5 25. 5 19. 9 0. 3 0. 8 1. 6 3. 1 2005 16. 3 32. 4 23. 2 0. 6 1. 3 1. 1 3. 7 2006 11. 4 45. 0 20. 3 0. 8 2. 0 4. 0 USDA-FSIS (http: //www. fsis. usda. gov/OPHS/haccp/salm 6 year. htm)

Number of Confirmed E. coli O 157: H 7 -Positive Ground Beef Samples by USDA-FSIS Calendar Year No. Positive/No. Samples (% Positive) 2000 2001 55/6, 375 59/7, 010 (0. 86%) (0. 84%) 2002 2003 2004 2005 55/7, 025 20/6, 584 14/8, 010 19/10, 976 (0. 78%) (0. 30%) (0. 17%) 2006 20/11, 779 (0. 17%) USDA-FSIS (http: //www. fsis. usda. gov/OPHS/ecoltest/tables 1. htm)

Incidence of cases of Campylobacter, Salmonella, and Escherichia coli O 157 infections under surveillance in the Foodborne Diseases Active Surveillance Network (Food Net), 2000 - 2006 Pathogen Year Campylobacter 2000 2001 2002 2003 2004 2005 15. 7 13. 8 13. 4 12. 6 12. 9 12. 3 2000 2001 2002 2003 2004 2005 14. 4 15. 1 16. 1 14. 5 14. 7 14. 6 6. 8 2000 2001 2002 2003 2004 2005 2. 0 1. 6 1. 7 1. 1 0. 9 1. 1 1. 0 Salmonella E. coli O 157 No. of cases/100, 000 persons National Health Objective for 2010 U. S. Centers for Disease Control and Prevention

Risk Factors for Sporadic Campylobacter jejuni Infections in Rural Michigan (2000 - 01) ● Risk factors identified: ▲ Persons engaged in poultry husbandry had increased odds of campylobacteriosis (OR = 6. 88, 95% CI 1. 44 - 33. 0) ♦ Dose-response relationship between number of poultry contacts and campylobacteriosis ▲ Estimated 18% of Campylobacter cases occurring in rural areas are attributable to poultry husbandry R. Church Potter et al. Am. J. Publ. Health 93: 2118 -2123 (2003)

Risk Factors for Sporadic Campylobacter Infections in the United States (1998 – 99) Risk Factors Odds Population Attributable Fraction (%) Ratio Ate chicken prepared at a restaurant 2. 2 24 Ate nonpoultry meat prepared at a restaurant 1. 7 21 Had contact with animal stool 1. 4 6 Had pet puppy 3. 4 5 Had contact w/farm animals (person >12 yrs) 2. 0 4 Ate turkey prepared at restaurant 2. 5 4 Drank untreated water 3. 3 3 Ate undercooked or pink chicken 2. 1 3 21. 0 2 4. 3 1. 5 Had contact w/farm animals (person 2<12 yrs) Drank raw milk C. Friedman et al. Clin. Infect Dis. 38(Suppl 3): S 285 (2004)

Risk Factors for Acquiring Salmonella Typhimurium Infection (1996 – 97) ● Risk factors identified in a multivariate model: ▲ Receiving 1 antibiotic in the ACKSSu. T group during the 4 weeks preceding onset of illness (OR = 3. 1; 95% CI, 1. 3 7. 3) ▲ Traveling outside the United States during 5 days preceding illness (OR = 19. 4; 95% CI, 2. 2 - 172. 4) ▲ Eating fried eggs prepared outside the home (OR = 4. 2; 95% CI, 1. 4 - 12. 9) M. K. Glynn et al. Clin. Infect. Dis. 38 (Suppl 3): S 227 -S 236 (2004)

Risk Factors for Sporadic Salmonella Enteritidis Infections in the United States (1996 – 97) ● Risk factor identified: ▲ Chicken prepared outside the home (m. OR = 2. 8) ♦ Accounted for 27% of SE cases A. C. Kimura et al. Clin. Infect. Dis. 38 (Suppl 3): S 244 (2004)

Risk Factors for Sporadic E. coli O 157: H 7 Infections in the United States, 1996 -1997 Risk Factors Odds Ratio Population Attributable Risk (%) Ate at table-service restaurant 1. 7 20 Ate pink hamburger at home 5. 0 8 Ate pink hamburger away from home 5. 0 7 Visited farm with cows (persons ≥ 6 yrs) 10 8 Lived on or visited farm (persons < 6 yrs) 5. 2 6 Child ≤ 2 yrs of age in household (persons < 6 yrs) 5. 4 6 Used an immunosuppressive medication (persons ≥ 6 yrs) 11 H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3): S 271 (2004) 5

Fresh Produce Fresh Vegetables and Fruits Have Become Major Vehicles of Foodborne Pathogens, especially E. coli O 157: H 7

Categories of U. S. Foodborne Outbreaks 1996 - 2005 Food Category No. of Outbreaks No. of Cases Processed Foods 44 2, 957 Produce 64 8, 151 Sprouts 25 1, 565 Seafood 120 2, 567 Eggs 234 6, 572 FDA 2006

Foodborne Outbreaks Related to Fresh Produce, 1973 -1997: Specific Food Vehicles Implicated in 190 Outbreaks ● Generic or multiple: ● ● ● ● ● Lettuce Melon Seed sprouts Apple or orange juice Berry Tomato Green onion Carrot Other 105 outbreaks 25 13 11 11 9 3 3 2 8 88% of outbreaks with one specific vehicle S. Sivapalasingam et al. J. Food Protection 67: 2342 -2353 (2004)

Foodborne Outbreaks Reported to CDC 1998 -2002*: Spectrum of Produce Implicated in 249 Outbreaks ● Generic or multiple ● ● ● ● ● Lettuce Sprouts Juice Melon Tomato Berries Cilantro Mango Other produce items (*Preliminary information) CDC 144 outbreaks 22 14 10 9 8 6 4 4 17 67% of outbreaks with single vehicle

E. coli O 157: H 7 Outbreak Associated with Bagged Fresh Spinach (Aug – Sept 2006) ● 205 cases of E. coli O 157 infection in 26 states and Canada ▲ 31 cases of HUS, 103 hospitalizations, 3 deaths ● Implicated vehicle – Bagged fresh spinach (Baby Spinach) ▲ Outbreak E. coli O 157 strain isolated from 13 bags of baby spinach in 11 states ▲ Grown in Salinas Valley, California U. S. Food and Drug Administration (Sept 28, 06) www. fda. gov/bbs/topics/NEWS/2006/NEW 01466. html California Food Emergency Response Team. Final Report, Investigation of an Escherichia coli O 157: H 7 Outbreak Associated with Dole Pre. Packaged Spinach (March 21, 2007)

E. coli O 157: H 7 Outbreak Associated with Bagged Fresh Spinach ● Traced to 50 -acre plot on the Paicines Ranch in San Benito County, CA ▲ Plot was in the second year of a 3 -year transition to organic production; most of land on this ranch used for cattle grazing (grass-fed beef) ▲ 45 of 351 (13%) of environmental samples in and around the Paicines Ranch were E. coli O 157: H 7 -positive ♦ Outbreak strain of E. coli O 157 confirmed from 26 of 45 E. coli O 157: H 7 -positive samples ♦ These were from cattle feces (15 samples), wild pig (7 samples), stream water (2 samples) and soil (2 samples)

E. coli O 157: H 7 Salinas Valley-Grown Spinach-Associated Outbreak ● Many creeks and streams near the Salinas Valley spinach fields were known to carry generic E. coli and E. coli O 157: H 7 ▲ Included were the Salinas River, Gabilan Creek, Towne Creek, Tembladero Slough and Old Salinas River Estuary ▲ Some waterways had ≥ 12, 000 E. coli/100 ml M. Cone Los Angeles Times, Sept 21, 2006

E. coli O 157: H 7 Outbreak Associated with Bagged Lettuce (Taco Johns) (December 2006) ● 81 cases of E. coli O 157 infection in 3 states ▲ 2 cases of HUS, 26 hospitalizations ● Implicated vehicle – Bagged, fresh-cut lettuce ▲ Grown in California’s Central Valley ▲ Outbreak E. coli O 157: H 7 strain isolated from 2 environmental samples from 2 dairy farms near lettucegrowing area U. S. Food and Drug Administration www. fda. gov/bbs/topics/NEWS/2007/NEW 01546. html

Persistence of E. coli O 157 on Vegetables and in Soil ● E. coli O 157 survival on produce: ▲ Parsley – 177 days ▲ Carrots – 175 days ▲ Onions – 84 days ▲ Leaf Lettuce – 77 days ● E. coli O 157 survival in soil: ▲ Parsley – 217 days ▲ Carrots – 196 days ▲ Onions – 168 days ▲ Leaf lettuce – 154 days M. Islam et al. , J. Food Protect. 67: 1365 (2004); Food Microbiology 22: 63 (2005)

● Once E. coli O 157: H 7 are introduced into soil or onto seedlings, either via contaminated irrigation water or compost, these bacteria can contaminate for months the vegetables and soil in which vegetables are grown

Public Health Issues Associated with Antibiotic-Resistant Foodborne Pathogens ● ● May be failure of drug treatment by critical antibiotics needed for human therapy, especially important for systemic infections May be increased risk of infection to people taking antimicrobials to which pathogen is resistant May be more severe manifestations of illness associated with some drug-resistant pathogens ▲ For example, longer duration of illness, and more systemic infections and hospitalizations Possible co-selection of virulence traits (e. g. , toxin-encoding genes) associated with antimicrobial-resistant microbes

Clinical Importance of Selected Antibiotics Associated with Foodborne Pathogens ● ● Ceftriaxone -- drug choice (cephalosporin) for treatment of severe salmonellosis in humans, especially children Ceftiofur -- only cephalosporin approved for systemic use in food animals in the United States ▲ Ceftiofur-resistant microbes exhibit decreased susceptibility for extended-spectrum cephalosporins Erythromycin -- drug of choice for treatment of severe campylobacteriosis Ciprofloxacin -- used for the empirical treatment of gastroenteritis and is recommended for treatment of infections caused by macrolide (erythromycin) resistant campylobacters

Examples of Antibiotic-Resistant Foodborne Pathogens in the United States ● ● Multidrug-Resistant Non-Typhi Salmonella ▲ Salmonella Typhimurium DT 104 - R-type: ACSSu. T ♦ Five agents: ampicillin, chloramphinicol, streptomycin, sulfamethoxazole, tetracycline ▲ Salmonella Newport - R-type: MDR-Amp C ♦ Nine agents: ampicillin, chloramphenicol, streptomycin, sulfamethoxazole, tetracycline, amoxicillin-clavulanic acid, cephalothin, cefoxitin, ceftiofur, (and decreased susceptibility to ceftriaxone) Ciprofloxacin-resistant Campylobacter

Examples of Antibiotic-Resistant Foodborne Pathogens in the United States (Cont’d) ● ● NOT issue with E. coli O 157: H 7 ▲ Antibiotic treatment is contraindicated because of potential exacerbation of manifestations of illness (renal failure) Vancomycin-resistant Enterococcus faecium and E. faecalis ▲ Largely hospital-acquired infections in intensive care units; food not identified as major vehicle of transmission in USA

Antibiotic Treatment of Salmonella Infection ● Not needed for mild diarrhea ● Used to prevent complications in neonates, immunosuppressed, and persons > 50 years of age ● Life-saving in invasive infections (e. g. , meningitis) ● Important antibiotics include amoxicillin, ceftriaxone, ciprofloxacin, trimethoprim-sulfa

Dominant Multidrug-Resistant Salmonella from Humans in United States, 2002 ● Four multidrug-resistant strains accounted for 8% (169/2009) of non-Typhi Salmonella isolates from humans assayed by CDC NARMS ▲ S. Typhimurium R-type ACSSu. T (21% of all isolates of S. Typhimurium), includes MDR DT 104 ▲ S. Newport MDR-Amp C (22% of all isolates of S. Newport) ▲ S. Typhimurium R-type AKSSu. T (6% of all S. Typhimurium) ▲ S. Heidelberg R-type ACl. Cf. Cp (8% of all S. Heidelberg) Centers for Disease Control and Prevention National Antimicrobial Resistance Monitoring System for Enteric Bacteria, 2002

Risk Factors for Acquiring Multidrug-Resistant Salmonella Typhimurium DT 104 Infections in the United States ● ● Case-control study using Food. Net data for MDR S. Typhimurium infections between 1996 - 1997 Risk factors identified in a multivariate model: ▲ Receiving an antibiotic(s) in the ACKSSu. T group during the 4 weeks before illness (OR = 5. 5; 95% CI, 6. 3 - 23. 8) ▲ Consuming eggs prepared outside the home during 5 days preceding illness (OR = 4. 4; 95% CI, 1. 2 - 16. 6) M. K. Glynn et al. Clin. Infect. Dis. 38 (Suppl 3): S 227 -S 236 (2004)

Risk Factors for Acquiring Salmonella Typhimurium DT 104 Infection in Canada ● ● Case-control study between 1999 - 2000 of sporadic Canadian cases of diarrheal illness caused by S. Typhimurium DT 104 Risk factors included: ▲ Antibiotics taken within 4 wks before illness (OR = 5. 2, 95% CI 1. 8 - 15. 3) ▲ Living on a livestock farm (OR = 4. 9, 95% CI 1. 9 - 18. 9) ▲ Recent travel outside Canada (OR = 4. 1, 95% CI 1. 2 13. 8) K. Doré et al. Epidemiol. Infect. 132: 485 -493 (2004)

Multidrug-Resistant Salmonella Newport ● Increase in human cases of MDR-S. Newport infections from 0% in 1996 to 3% in 2002 of non. Typhi Salmonella cases ● Increase in S. Newport isolates associated with human infections that were MDR-Amp C, from 0% in 1996 -97 to 22% in 2002

Emergence of MDR Salmonella Newport Infections Resistant to Cephalosporins in the United States ● In Massachusetts, isolation of S. Newport MDR-Amp C among S. Newport isolates from humans increased from 0% in 1998 to 53% in 2001 ● Case-control study revealed Newport MDR-Amp C was: ▲ Domestically acquired ▲ Associated with exposure to a dairy farm A. Gupta et al. J. Infect. Dis. 188: 1707 -1716 (2003)

Vehicles of Outbreaks of S. Newport MDRAmp C Infection ● Outbreaks first reported in 1999 in United States ● Examples of food vehicles ▲ Unpasteurized cream ▲ Cheese made from unpasteurized milk ▲ Ground beef ▲ Tomatoes ▲ Turkey ▲ Cilantro ▲ Dish containing goat’s blood

Emergence of Multidrug-resistant Salmonella Newport in United States ● ● The incidence of S. Newport human illness increased markedly in the late 1990 s The increase in human S. Newport illness has been driven by an increase in a highly resistant strain, "Newport MDRAmp. C" Illness due to Newport MDR-Amp. C is also emerging in cattle Risk factors for human illness include contact with cattle and consumption of bovine products (e. g. , ground beef, unpasteurized cheese) Patricia Griffin, Centers for Disease Control and Prevention, CSTE Annual Meeting 2002

Comparison of S. Typhimurium DT 104 with S. Newport MDR-Amp C S. Typhimurium DT 104 S. Newport MDR-Amp C ● Illness in cattle ● Illness in persons in contact with cattle ● Illness in person in contact with cattle ● Bovine food vehicles (cheese, ground beef) ● Bovine food vehicles (cheese, ground beef ● R-type: ACSSu. T plus ● Resistance genes on chromosome ● Resistance genes on plasmid ● Epidemic in Europe (esp. 1990 2002) and present in USA ● Largely confined to USA

Recommendation by Some Public Health Scientists ● Establish “zero tolerance” for antibiotic-resistant Salmonella in ground beef

MDR Salmonella Paratyphi B var. Java Outbreak in Cattle ● MDR S. Java outbreak occurred in cattle in the United Kingdom ▲ MDR S. Java associated with tropical fish from Thailand put in cattle drinking water tanks to control algae ♦ Thailand aquaculture does not normally apply antibiotics directly to ponds ►Fish are fed chicken manure and chickens are fed antibiotics ■ Antibiotics inducing drug resistance likely present in chicken feces fed to fish John Threlfall, Society for General Microbiology Annual Meeting, Edinburgh, Scotland, April 2005

Changes in the incidence of foodborne illness, and corresponding changes in prevalence of antibiotic-resistant foodborne pathogens causing human illnesses in U. S. Human case rate (per 100, 000) Year(s) Organism 1996 -98 Salmonella 15. 9 2004 Salmonella 14. 7 1996 -98 Salmonella Typhimurium 4. 9 2004 Salmonella Typhimurium 2. 9 1996 -98 Salmonella Newport 1. 2 2004 Salmonella Newport 1. 7 1996 -98 Campylobacter 18. 7 2004 Campylobacter 12. 9 Relative decrease or increase 8% decrease 41% increase 31% decrease % Resistant Human case rate (per 100, 000) 31% (2 or more antibiotics, 1996) 4. 9 16% (2 or more antibiotics, 2002) 2. 4 34% (ACSSu. T, 1996) 1. 7 21% (ACSSu. T, 2002) 0. 6 8% (2 or more antibiotics, 1996) 0. 1 25% (2 or more antibiotics, 2002) 0. 4 13% (ciprofloxacin resistance, 1997) 2. 4 20% (ciprofloxacin resistance, 2002) 17. 7% (ciprofloxacin resistance, 2003) 2. 6 Relative decrease or increase 51% decrease 65% decrease 300% increase 8% increase

Risk Analysis for Regulatory Decisions on Antimicrobial Usage: Example of Unintended Consequences? ● Risk management action in Europe to eliminate use of antibiotics for feed efficiency and growth promotion may have resulted in increased intestinal disease in animals and concomitant use of more therapeutic antibiotics with resultant increase in resistance ▲ Resistance among some pathogens (tet. R S. Typhimurium, amp. R S. Typhimurium, tet. R C. jejuni, cry. R C. jejuni, amp. R E. coli) have increased in Europe

Risk Analysis for Regulatory Decisions on Antimicrobial Usage: Example of Unintended Consequences? ▲ Example, Denmark banned in 1998 use of antibiotics for growth promotion of animals ♦ Total use of antibiotics in animals in Denmark decreased 30% between 1997 (before ban) and 2004, there was a 41% increase in therapeutic uses between 1999 (after ban) and 2004 ►Between 1999 -2004, tet. R and amp. R of S. Typhimurium from pigs increased, from chickens increased from 0% in 1997 to 17% in 2004 and from ill humans increased from 18% to 46%

Risk Analysis for Regulatory Decisions on Antimicrobial Usage ● ● EU banned antibiotic use in feed for growth promotion on the basis of the precautionary principle which is employed when scientific information is insufficient, inconclusive or uncertain ▲ Sweeping risk management measures that are proposed for a certain classification of use (e. g. , growth promotion) can be draconian and without predictable results ▲ Analysis would best be carried out on a case-by-case basis and driven by product-specific, science-based risk assessments IFT Expert Panel concluded that thorough risk assessments should be used to guide selection of risk management actions so that unintended consequences are minimized

Concluding Comments ● Salmonella, Campylobacter and E. coli O 157: H 7 are major causes of foodborne illness ● Livestock and poultry are important vehicles for transmitting these pathogens to foods and on to humans ● Manure is a major vehicle for transmitting zoonotic pathogens to food ● Salmonella contamination of poultry, especially ground products, is considerably greater than that of beef and pork ● E. coli O 157: H 7 and Salmonella contamination of produce (likely from direct or indirect exposure to manure) is a growing concern

Concluding Comments ● Growing public health concerns regarding antimicrobial-resistant zoonotic foodborne pathogens ▲ MDR Salmonella comprise ca. 10% of non-Typhi Salmonella isolates from humans ▲ Major increase in incidence of human cases of MDR S. Newport infections (ca. 300%) ▲ Major decrease in incidence of human cases of Campylobacter enteritis (ca. 31%) but increase in incidence of ciprofloxacin-resistant Campylobacter cases (ca. 8%) However: ▲ Major decrease in incidence of human cases of S. Typhimurium DT 104 infections (ca. 65%) and in prevalence of S. Typhimurium DT 104 in livestock and poultry (ca. 10%)

Concluding Comments Putting the Antibiotic Resistance Issue in Livestock in Perspective ● Minimizing the use of antimicrobials in agriculture should be weighed against the likelihood of increasing the level of pathogens in food ● Sick animals must be treated for humanitarian reasons ● Prudent use of antibiotics in both human and animal medicine is essential ● Thorough risk assessments should be used to guide risk management actions