Foodborne Illnesses and Antibiotic Resistance Associated with Zoonotic Pathogens

1
Foodborne Illnesses and Antibiotic Resistance
Associated with Zoonotic Pathogens

• Michael Doyle

2
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
  antibiotic-resistant foodborne pathogens

3
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

4
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 O157H7 - estimated 73,000 cases/yr
• P. Mead et al. Emerging Infect. Dis. 5607-625
  (1999)

5
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 O157H7 (principally
  cattle)

6
Primary Sources of Enteric Foodborne Pathogens
that Contaminate Foods

• Animal manure
• Human feces

7
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

8
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

9
The U.S. Manure Glut (1997 estimates)

• Animal Solid Waste
  (Tons/yr)
• Cattle 1,229,190,000
• Hogs 116,652,300
• Chickens 14,394,000
• Turkeys 5,425,000
• TOTAL 1.36 billion

10
Percentage of Great Britain Livestock Manures
Contaminated with Zoonotic Microbes
Cattle Cattle Swine Swine Poultry Poultry Sheep Sheep
Pathogen Fresha Storedb Fresh Stored Fresh Stored Fresh Stored
E. coli O157H7 13.2 9.1 11.9 15.5 NDc ND 20.8 22.2
Salmonella 7.7 10.0 7.9 5.2 17.9 11.5 8.3 11.1
Campylobacter 12.8 9.8 13.5 10.3 19.4 7.7 20.8 11.1

a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined
M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004)
11
Cell Numbers of Zoonotic Pathogens in British
Livestock Manures
Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen Cell No. (CFU/g) of pathogen
Cattle Cattle Swine Swine Poultry Poultry Sheep Sheep
Pathogen Fresha Storedb Fresh Stored Fresh Stored Fresh Stored
E. coli O157
Geo Mean 1X103 3X102 4X103 1X103 NDc ND 8X102 3X102
Max 3X108 8X104 8X105 2X104 ND ND 5X104 5X103
Salmonella
Geo Mean 2X103 3X103 6X102 6X102 2X102 4X103 7X102 6X103
Max 6X105 7X106 8X104 2X103 2X104 8X103 2X103 6X103
Campylobacter
Geo Mean 3X102 5X102 3X102 2X103 3X102 6X102 4X102 1X102
Max 2X105 2X105 2X104 1X105 3X104 9X102 2X103 1X102
a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined a Fresh, collected from location in which deposited b Stored, collected from lagoon or farm yard manure heap c ND, not determined
M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004) M. L. Hutchison et al. Lett. Appl. Microbiol. 39207-214 (2004)
12
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
  Salmonella-positive samples than NY
• Highest Salmonella shedding in summer, then fall,
  spring and winter
• C. P. Fossler et al. Prev. Vet. Med. 6739-53
  (2005)

13
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. 6739-53
  (2005)

14
Prevalence of Salmonella in Meat and Poultry
Determined by USDA-FSIS Pathogen Reduction/HACCP
Verification Testing Program
Calendar Year Broiler Carcasses Broiler Carcasses Ground Chicken Ground Turkey Steer Heifer Carcasses Bull Cow Carcasses Ground Beef Hog Carcasses
( Positive) ( Positive) ( Positive) ( Positive) ( Positive) ( Positive) ( Positive)
Baseline Baseline
(Pre-1998) (Pre-1998) 20 44.6 49.9 1.0 2.7 7.5 8.7
1998 1998 10.8 4.2 36.5 0 1.1 6.4 5.8
1999 1999 11.4 16.2 31.6 0.3 2.2 4.3 9.8
2000 2000 9.1 13.8 25.7 0.4 2.2 3.3 6.2
2001 2001 11.9 19.5 26.2 0.6 2.4 2.8 3.8
2002 2002 11.5 29.1 17.9 0.3 1.7 2.6 3.2
2003 2003 12.8 35.5 25.4 0.4 1.5 1.7 2.5
2004 2004 13.5 25.5 19.9 0.3 0.8 1.6 3.1
2005 2005 16.3 32.4 23.2 0.6 1.3 1.1 3.7
2006 2006 11.4 45.0 20.3 0.3 0.8 2.0 4.0
USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/haccp/salm6year.htm)
15
Number of Confirmed E. coli O157H7-Positive
Ground Beef Samples by USDA-FSIS
Calendar Year No. Positive/No. Samples ( Positive) No. Positive/No. Samples ( Positive) No. Positive/No. Samples ( Positive)

2000 2000 55/6,375 (0.86)
2001 2001 59/7,010 (0.84)
2002 2002 55/7,025 (0.78)
2003 2003 20/6,584 (0.30)
2004 2004 14/8,010 (0.17)
2005 2005 19/10,976 (0.17)
2006 2006 20/11,779 (0.17)

USDA-FSIS (http//www.fsis.usda.gov/OPHS/ecoltest/tables1.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/ecoltest/tables1.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/ecoltest/tables1.htm) USDA-FSIS (http//www.fsis.usda.gov/OPHS/ecoltest/tables1.htm)
16
Incidence of cases of Campylobacter, Salmonella,
and Escherichia coli O157 infections under
surveillance in the Foodborne Diseases Active
Surveillance Network (Food Net), 2000 - 2006
National Health
Pathogen Year No. of cases/100,000 persons Objective for 2010

Campylobacter 2000 15.7
2001 13.8
2002 13.4
2003 12.6
2004 12.9
2005 12.9 12.3

Salmonella 2000 14.4
2001 15.1
2002 16.1
2003 14.5
2004 14.7
2005 14.6 6.8

E. coli O157 2000 2.0
2001 1.6
2002 1.7
2003 1.1
2004 0.9
2005 1.1 1.0

U.S. Centers for Disease Control and Prevention U.S. Centers for Disease Control and Prevention U.S. Centers for Disease Control and Prevention U.S. Centers for Disease Control and Prevention
17
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
  932118-2123 (2003)

18
Risk Factors for Sporadic Campylobacter
Infections in the United States (1998 99)
Risk Factors Odds Ratio Population Attributable Fraction ()
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 gt12 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
Had contact w/farm animals (person 2lt12 yrs) 21.0 2
Drank raw milk 4.3 1.5
C. Friedman et al. Clin. Infect Dis. 38(Suppl 3) S285 (2004) C. Friedman et al. Clin. Infect Dis. 38(Suppl 3) S285 (2004) C. Friedman et al. Clin. Infect Dis. 38(Suppl 3) S285 (2004)
19
Risk Factors for Acquiring Salmonella Typhimurium
Infection (1996 97)

• Risk factors identified in a multivariate model
• Receiving 1 antibiotic in the ACKSSuT 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)S227-S236
• (2004)

20
Risk Factors for Sporadic Salmonella Enteritidis
Infections in the United States (1996 97)

• Risk factor identified
• Chicken prepared outside the home (mOR 2.8)
• Accounted for 27 of SE cases
• A. C. Kimura et al. Clin. Infect. Dis. 38 (Suppl
  3) S244 (2004)

21
Risk Factors for Sporadic E. coli O157H7 Infections in the United States, 1996-1997 Risk Factors for Sporadic E. coli O157H7 Infections in the United States, 1996-1997 Risk Factors for Sporadic E. coli O157H7 Infections in the United States, 1996-1997 Risk Factors for Sporadic E. coli O157H7 Infections in the United States, 1996-1997 Risk Factors for Sporadic E. coli O157H7 Infections in the United States, 1996-1997
Risk Factors Odds Ratio Odds Ratio Population Attributable Risk () Population Attributable Risk ()
Ate at table-service restaurant Ate at table-service restaurant 1.7 1.7 20
Ate pink hamburger at home Ate pink hamburger at home 5.0 5.0 8
Ate pink hamburger away from home Ate pink hamburger away from home 5.0 5.0 7
Visited farm with cows (persons 6 yrs) Visited farm with cows (persons 6 yrs) 10 10 8
Lived on or visited farm (persons lt 6 yrs) Lived on or visited farm (persons lt 6 yrs) 5.2 5.2 6
Child 2 yrs of age in household (persons lt 6 yrs) Child 2 yrs of age in household (persons lt 6 yrs) 5.4 5.4 6
Used an immunosuppressive medication (persons 6 yrs) Used an immunosuppressive medication (persons 6 yrs) 11 11 5
H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3) S271 (2004) H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3) S271 (2004) H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3) S271 (2004) H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3) S271 (2004) H. D. Kassenborg et al. Clin. Infect. Dis. 38 (Suppl 3) S271 (2004)
22
Fresh Produce

• Fresh Vegetables and Fruits Have Become
• Major Vehicles of Foodborne Pathogens,
• especially E. coli O157H7

23
Categories of U.S. Foodborne Outbreaks1996 - 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
24
Foodborne Outbreaks Related to Fresh Produce,
1973-1997 Specific Food Vehicles Implicated in
190 Outbreaks

• Generic or multiple 105 outbreaks
• Lettuce 25
• Melon 13
• Seed sprouts 11
• Apple or orange juice 11
• Berry 9
• Tomato 3
• Green onion 3
• Carrot 2
• Other 8
• S. Sivapalasingam et al. J. Food Protection
  672342-2353 (2004)

88 of outbreaks with one specific vehicle
25
Foodborne Outbreaks Reported to CDC 1998-2002
Spectrum of Produce Implicated in 249 Outbreaks

• Generic or multiple 144 outbreaks
• Lettuce 22
• Sprouts 14
• Juice 10
• Melon 9
• Tomato 8
• Berries 6
• Cilantro 4
• Mango 4
• Other produce items 17

67 of outbreaks with single vehicle
(Preliminary information) CDC
26
E. coli O157H7 Outbreak Associated with Bagged
Fresh Spinach (Aug Sept 2006)

• 205 cases of E. coli O157 infection in 26 states
  and Canada
• 31 cases of HUS, 103 hospitalizations, 3 deaths
• Implicated vehicle Bagged fresh spinach (Baby
  Spinach)
• Outbreak E. coli O157 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/NEW01466.html
• California Food Emergency Response Team. Final
  Report, Investigation of an Escherichia coli
  O157H7 Outbreak Associated with Dole
  Pre-Packaged Spinach (March 21, 2007)

27
E. coli O157H7 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
  O157H7-positive
• Outbreak strain of E. coli O157 confirmed from 26
  of 45 E. coli O157H7-positive samples
• These were from cattle feces (15 samples), wild
  pig (7 samples), stream water (2 samples) and
  soil (2 samples)

28
E. coli O157H7 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 O157H7
• 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

29
E. coli O157H7 Outbreak Associated with Bagged
Lettuce (Taco Johns) (December 2006)

• 81 cases of E. coli O157 infection in 3 states
• 2 cases of HUS, 26 hospitalizations
• Implicated vehicle Bagged, fresh-cut lettuce
• Grown in Californias Central Valley
• Outbreak E. coli O157H7 strain isolated from 2
  environmental samples from 2 dairy farms near
  lettuce-growing area
• U.S. Food and Drug Administration
• www.fda.gov/bbs/topics/NEWS/2007/NEW01546.html

30
Persistence of E. coli O157 on Vegetables and in
Soil

• E. coli O157 survival on produce
• Parsley 177 days
• Carrots 175 days
• Onions 84 days
• Leaf Lettuce 77 days
• E. coli O157 survival in soil
• Parsley 217 days
• Carrots 196 days
• Onions 168 days
• Leaf lettuce 154 days
• M. Islam et al., J. Food Protect. 671365 (2004)
  Food Microbiology 2263 (2005)

31

• Once E. coli O157H7 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

32
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

33
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

34
Examples of Antibiotic-Resistant Foodborne
Pathogens in the United States

• Multidrug-Resistant Non-Typhi Salmonella
• Salmonella Typhimurium DT104 - R-type ACSSuT
• 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

35
Examples of Antibiotic-Resistant Foodborne
Pathogens in the United States (Contd)

• NOT issue with E. coli O157H7
• 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

36
Antibiotic Treatment of Salmonella Infection

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

37
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 ACSSuT (21 of all isolates
  of S. Typhimurium), includes MDR DT104
• S. Newport MDR-Amp C (22 of all isolates of S.
  Newport)
• S. Typhimurium R-type AKSSuT (6 of all S.
  Typhimurium)
• S. Heidelberg R-type AClCfCp (8 of all S.
  Heidelberg)
• Centers for Disease Control and Prevention
  National Antimicrobial
• Resistance Monitoring System for Enteric
  Bacteria, 2002

38
Risk Factors for Acquiring Multidrug-Resistant
Salmonella Typhimurium DT104 Infections in the
United States

• Case-control study using FoodNet data for MDR S.
  Typhimurium infections between 1996 - 1997
• Risk factors identified in a multivariate model
• Receiving an antibiotic(s) in the ACKSSuT 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)S227-S236
• (2004)

39
Risk Factors for Acquiring Salmonella Typhimurium
DT104 Infection in Canada

• Case-control study between 1999 - 2000 of
  sporadic Canadian cases of diarrheal illness
  caused by S. Typhimurium DT104
• 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. 132485-493
  (2004)

40
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

41
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. 1881707-1716
  (2003)

42
Vehicles of Outbreaks of S. Newport MDR-Amp 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 goats blood

43
Emergence of Multidrug-resistant Salmonella
Newport in United States

• The incidence of S. Newport human illness
  increased markedly in the late 1990s
• The increase in human S. Newport illness has been
  driven by an increase in a highly resistant
  strain, "Newport MDR-AmpC"
• Illness due to Newport MDR-AmpC 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

44
Comparison of S. Typhimurium DT104 with S.
Newport MDR-Amp C
S. Typhimurium DT104 S. Newport MDR-Amp C
? Illness in cattle ? 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 ACSSuT ? R-type ACSSuT plus
? Resistance genes on chromosome ? Resistance genes on plasmid
? Epidemic in Europe (esp. 1990 - 2002) and present in USA ? Largely confined to USA

45
Recommendation by Some Public Health Scientists

• Establish zero tolerance for antibiotic-resistan
  t Salmonella in ground beef

46
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

47
Changes in the incidence of foodborne illness,
and corresponding changes in prevalence of
antibiotic-resistant foodborne pathogens causing
human illnesses in U.S.
Year(s) Organism Human case rate (per 100,000) Relative decrease or increase Resistant Human case rate (per 100,000) Relative decrease or increase
1996-98 Salmonella 15.9 31 (2 or more antibiotics, 1996) 4.9
2004 Salmonella 14.7 8 decrease 16 (2 or more antibiotics, 2002) 2.4 51 decrease

1996-98 Salmonella Typhimurium 4.9 34 (ACSSuT, 1996) 1.7
2004 Salmonella Typhimurium 2.9 41 decrease 21 (ACSSuT, 2002) 0.6 65 decrease

1996-98 Salmonella Newport 1.2 8 (2 or more antibiotics, 1996) 0.1
2004 Salmonella Newport 1.7 41 increase 25 (2 or more antibiotics, 2002) 0.4 300 increase

1996-98 Campylobacter 18.7 13 (ciprofloxacin resistance, 1997) 2.4
2004 Campylobacter 12.9 31 decrease 20 (ciprofloxacin resistance, 2002) 17.7 (ciprofloxacin resistance, 2003) 2.6 8 increase
48
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 (tetR S.
  Typhimurium, ampR S. Typhimurium, tetR C. jejuni,
  cryR C. jejuni, ampR E. coli) have increased in
  Europe

49
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, tetR and ampR 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

50
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

51
Concluding Comments

• Salmonella, Campylobacter and E. coli O157H7 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 O157H7 and Salmonella contamination of
  produce (likely from direct or indirect exposure
  to manure) is a growing concern

52
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 DT104 infections (ca. 65) and in
  prevalence of S. Typhimurium DT104 in livestock
  and poultry (ca. 10)

53
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