Public Health Concerns About Resistant Foodborne Infections - Dr. Robert Tauxe, Deputy Director, Division of Foodborne, Waterborne and Environmental Infections, Centers for Disease Control and Prevention, from the 2013 NIAA Symposium Bridging the Gap Between Animal Health and Human Health, November 12-14, 2013, Kansas City, MO, USA. More presentations at http://www.trufflemedia.com/agmedia/conference/2013-niaa-antibiotics-bridging-the-gap-animal-health-human-health

1. Public health concerns about resistant foodborne
infections
Antibiotics Symposium
National Institute for Animal Agriculture
Kansas City , Missouri
November 12, 2013
Robert Tauxe, MD, MPH
Deputy Director,
Division of Foodborne, Waterborne, and Environmental Diseases
National Center for Emerging and Zoonotic Infectious Diseases
Centers for Disease Control and Prevention

2. Antimicrobial treatments have been critical in
human and veterinary medicine for 60+ years
Antimicrobial resistance a challenge for almost as long
Emerges in settings where antimicrobials are used
In a variety of bacteria, viruses, fungi, parasites
Sometimes spreads from one bacterial strain to another
Central issue for managing infections of all kinds

3. One Health: The Way Forward
A multidisciplinary collaborative effort that
focuses on the interconnectedness of a large
ecosystem to achieve optimal health of
humans, animals, and environments across
the world.

4. CDC report released
September 17, 2013
18 pathogens
Burden
•2,049,000 illnesses
•23,000 deaths
Foodborne pathogens
•4 of the 18 often transmitted
through foods
•2 with animal reservoirs
•2 with human reservoirs
http://www.cdc.gov/drugresistance/threat-report-2013

5. Annual public health burden of resistant
foodborne infections
 Resistant to principal clinical agents used for treatment
Pathogen
Percent
Resistant
# illnesses/
year
# deaths/
Year
Campylobacter
24%
310,000
28
Non-typhoidal
Salmonella
8%
100,000
38
Salmonella Typhi
67%
3,800
<5
Shigella
6%
27,000
<5
441,000
66-70
Total
CDC 2013 Antibiotic Resistance Threats

6. Tracking the public health challenge of foodborne
antimicrobial resistance at CDC
 1970’s: Periodic surveys of Salmonella and Shigella
 1980’s: Outbreaks of resistant infections
 1996: National Antimicrobial Resistance Monitoring System for Enteric
Bacteria (NARMS), a collaborative effort
• USDA/FSIS - animals at slaughter
• FDA Center for Veterinary Medicine – retail meats
• CDC – human clinical cases
• Human, animal strains from all 50 states
• Retail food isolates from 14 states
• Standard panels of antimicrobial agents
(See cdc.gov/NARMS for 2011 Annual Report, testing details)

7. ?
Bacteria tracked in NARMS
Humans – CDC
Animals - USDA
Non-Typhi Salmonella (1996)
Non-Typhi Salmonella (1997)
E. coli O157:H7 (1996)
Campylobacter (1998)
Campylobacter (1997)
E. coli (2000)
Salmonella Typhi (1999)
Enterococcus (2003)
Shigella (1999)
Vibrio other than V. cholerae, (2009)
Retail meats – FDA (2002)
Non-Typhi Salmonella
Campylobacter
E. coli
Enterococcus

8. Emergence of drug resistant strains of concern:
Salmonella and Campylobacter

9. Recent multistate outbreaks of resistant
Salmonella infections
Year
Serotype
vehicle
cases
states
% hosp
resistance
2010
Typhimurium
Ground beef
20
7
47
AKSSuFoxCx
2011
Heidelberg
Ground
turkey
136
34
39
ASSuT
2012
Heidelberg
Chicken
134
13
31
Variable*
2013
Heidelberg
Chicken
362
21
38
Variable*
* Polyclonal outbreak, varied patterns,
Some strains had no resistance at all
Some strains resistant to clinically important drugs
2013 testing is incomplete

10. What connects antibiotic use in animals with
human health?
 Use of antibiotics in food producing animals selects for antibiotic-resistant bacteria (including ones pathogenic to humans)
Resistant bacteria can be transmitted from food –producing animals to humans through the food supply
Resistant bacterial pathogens can cause illness in humans
Infections caused by resistant bacteria can result in adverse health consequences for humans

11. Why are resistant strains of particular concern?
 When treatment is needed, early empiric treatment may fail, and treatment choices will be limited
 Increased morbidity and mortality
• Longer illnesses
• More invasive infections
• More likely to be hospitalized
• More deaths
 When resistance is located on a mobile genetic element, it may be transferred to other bacteria horizontally
Mølbak 2005 Clin Infect Dis 41:1613-20

12. Why are resistant strains of particular concern?
(continued)
Epidemiological observations, and a well-established animal model

Resistant strains have a selective advantage in individuals who are taking antimicrobial for other reasons

Colonization with a resistant pathogen may convert to overt disease if the individual takes an antibiotic to which it is resistant
• Illness in individuals already ill for other reasons
• More clinical cases: Proportion of illness attributable to resistance estimated at 3-26% for Salmonella (=58,000 more illnesses)
Barza 2002 Clin Infect Dis 34:S123-125, S126-130

13. FDA withdrew
poultry
enrofloxacin
approval
Fluoroquinolones
first approved for
use in poultry
Ciprofloxacin
approved for
human use
Pilot study
0.0%

14. Non-Typhoidal Salmonella

Resistance to ceftriaxone (2009-2011)
• 2.9% of all isolates
• 17.9% of Heidelberg isolates

Decreased susceptibility to ciprofloxacin (2009-2011)
• 2.7% of all isolates
• Approximately half were serotype Enteritidis
• Most are travel-associated

Penta-resistance (e.g. ACSSuT)
• 8.2% in 2002  4.6% in 2011 all isolates
• 23%  21% of Typhimurium
• 23%  4% of Newport
NARMS 2009-2011 data, 2011 NARMS report

15. Ceftriaxone resistance in
Salmonella serotype Heidelberg, 1996-2012*
32%
3%
0%
*2012 human data are preliminary; only 10 ground turkey isolates were tested in 2009 and 11 retail chicken
isolates in 2002 and 2011

16. Salmonella Heidelberg in Québec
Ceftiofur resistance – 2003-2008
Cft R S. Heidelberg
was common in
poultry meat, but
was not found in
beef or pork
2005-2006:
Poultry industry
in Québec
voluntarily halted
use of ceftiofur
in eggs
Dutil et al. 2010 EID 16: 48-54

17. Microbiological characterization of non-typhoidal
Salmonella strains from food animals, retail meat,
and people in US, 2008
 Decreased susceptibility to ceftriaxone/ceftiofur (MIC>2μg/L)
 blaCMY genes, usually combined with other resistance genes
• Human:
4.6% (Newport, Typhimurium, Heidelberg, Agona)
• Retail meat: 15.7% (Typhimurium, Heidelberg, Kentucky, Newport)
• Animals:
10.6% (Dublin, Kentucky, Newport, Typhimurium)
 Conclude:
• substantial overlap in strains across sources
• same CMY gene is found in all three sources
• same CMY gene appearing in several serotypes
Karlsson 2013 Microbial Drug Resist 19:191-197

18. CMY2 genes in Salmonella Heidelberg are
plasmid-borne, 2009
 The CMY2 gene for ceftiofur/ceftriaxone (Cft/Cx) resistance was first described on a plasmid that easily transferred between Salmonella and E. coli (1998-9)
 2009: S Heidelberg that was Cft/Cx-resistant blaCMY +
• 47 strains found in NARMS
• All 47 were plasmid encoded on plasmids
• 41 of the 47 plasmids were Inc type 1, with two closely related sequence types
• Same plasmid found in variety of Heidelberg strains
• 26 of the 29 animal and meat isolates were from chicken
The 2009 increase in Cft/Cx resistance is related to spread of a plasmid among various Heidelberg strains in poultry, rather than to the clonal expansion of one strain
Winokur 2001 AAC 45:2716-2722
Folster et al 2012 FPD19:638-645

19. Salmonella Typhi

20. Shigella
 Ciprofloxacin resistance
 2011: resistance to Amp 34%, Tet 41%, TMP-SXT 67%
 Reduced susceptibility to azithromycin:
• 3.1% in 2011 and 4.3%* in 2012
*preliminary data

21. Challenges in other parts of the world
 Campylobacter in Europe: Cipro resistance in
• 52% of strains from humans
• 50% of strains from poultry
• 80% of strains from international travelers
 Salmonella Typhimurium and Enteritidis in eastern Africa
• Recurrent outbreaks, sometimes nosocomial
• Highly multi-resistant strains
• Invasive infections with higher mortality (typhoid-like)
Taiwan: Salmonella Choleraesuis:
• Increase in human infections in late 1990’s
• Resistant, up to 60% cipro R, some to ceftriaxone (CMY2)
• Highly invasive, presenting with aortitis, septic shock
• Related to epizootic in pigs with same organism
WHO Campylobacter Consultation 2013
2013 Kotloff Lancet; 2008 Gordon CID; 2011 Su EID;

22. Salmonella Kentucky in Africa/Asia/Europe
Since 1960, Pasteur Institute tracking Salmonella Kentucky
• First: infections in travelers from Tunisia
• 1990’s: from Egypt
• 2000’s: from India
Progressive increase in resistance (since 1990’s)
2008: Appeared in Polish turkey flocks, meat and consumers
Since then in turkey flocks and meat in Germany and France
One genetic lineage: now R to ASSuTTmpGentCip, and
sometimes has CMY2
LeHello 2013 Lancet Infectious Disease 13:652-679
Wasyl 2012 Food Research Int 45:958-961

23. CDC is addressing the challenge of resistant
foodborne infections by
Promoting prevention
Tracking resistance through NARMS
Making that information more available more quickly
Refining estimates of the health impact of resistance
Making realtime resistance data part of outbreak investigations
Refining understanding of sources and mechanisms of
• resistance genes
• and resistant bacterial strains

24. Addressing public health concern about resistant
infections with Shigella
Management of Shigella infections in children has changed
Until the 1990’s, often routine to
• treat all cases aggressively, no matter how mild
• treat exposed family members
• prophylaxe other children in the child care center
 Rapid increase in resistance to Amp, Tmp-Sxt, Nalidixic acid
 In the 1990’s, routine changed to:
• reserve treatment for severe illnesses only
• provide family members with soap and handwashing advice
• Isolate ill children and increase hygiene in child care centers
Tuttle et al 1993 Inf Dis Clin Pract 2:55-59

25. Addressing the public health concern about resistant
foodborne zoonotic infections
Expertise in animal health and management is vital to
Reduce introduction of resistant strains into production
• Breeder stock, hatcheries
• Animal feed sources
• Water, environment, employees, etc.
 Consider conditions that foster selection of resistance and
spread of resistant organisms
• Antimicrobial use that is sub-therapeutic, repeated,
widespread, or unnecessary
• Management practices that spread illness among animals
 Implement prevention measures
• Judicious antimicrobial use
• Alternate prevention steps
• Reduce food contamination

26. Antimicrobial resistance in foodborne infections in
the 21st century
 Substantial challenge to human and animal health
The burden is substantial, but perhaps not irreversible
Non-judicious medical use is being addressed with major efforts
Foodborne pathogens resistant to drugs important in human medicine, whether
related to human use or agricultural use
Limit the emergence of resistance, and prolong effectiveness of current antibiotics
• Judicious use for food animals supervised by a veterinarian
• Measures that prevent spread and food contamination
We all want
• Food to be safer
• Those who eat it to be healthier
• People to have confidence in food supply

27. Thank you
The findings and conclusions in this presentation are
those of the author and do not necessarily represent
the views of the Centers for Disease Control and
Prevention

28. Our websites
Antimicrobial resistance:
www.cdc.gov/drugresistance/index.html
Our Programs:
NARMS:
www.cdc.gov/NARMS
FoodNet:
www.cdc.gov/foodnet
PulseNet: www.cdc.gov/pulsenet
FoodCORE: www.cdc.gov/ncezid/dfwed/orpb/foodcore/index.html
Specific pathogens:
E. coli:
www.cdc.gov/ecoli
Salmonella: www.cdc.gov/salmonella
Listeria:
www.cdc.gov/listeria
Multistate foodborne outbreaks:
www.cdc.gov/outbreaknet/outbreaks.html
General information about foodborne diseases:
www.cdc.gov/foodsafety
www.foodsafety.gov

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700 incidents, 6 deaths
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blamed customers
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Loss of $100 million in 1987
US sales dropped 84% by 1991
VW bought Audi
Later corporate response:
Recalled 5 years of production
Retired the A5000 model
Re-engineered pedals to be
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New interlock required foot
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