Robert Tauxe, MD, MPH

Deputy Director, Division of Foodborne, Waterborne, and Environmental DiseasesNational Center for Emerging and Zoonotic Infectious Diseases

Centers for Disease Control and Prevention

Public health concerns about resistant foodborne infections

Antibiotics SymposiumNational Institute for Animal Agriculture

Kansas City , MissouriKansas City , Missouri

November 12, 2013November 12, 2013

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

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.

CDC report releasedSeptember 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

Annual public health burden of resistant foodborne infections

CDC 2013 Antibiotic Resistance Threats

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

Total 441,000 66-70

Resistant to principal clinical agents used for treatment

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)

Bacteria tracked in NARMS

Humans – CDCNon-Typhi Salmonella (1996)E. coli O157:H7 (1996)Campylobacter (1997)Salmonella Typhi (1999)Shigella (1999)Vibrio other than V. cholerae, (2009)

Animals - USDANon-Typhi Salmonella (1997)Campylobacter (1998)E. coli (2000)Enterococcus (2003)

Retail meats – FDA (2002)Non-Typhi SalmonellaCampylobacter E. coli Enterococcus

?

Emergence of drug resistant strains of concern:Salmonella and Campylobacter

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

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

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

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

FDA withdrew poultry

enrofloxacin approval

Fluoroquinolones first approved for

use in poultry

Ciprofloxacin approved for human use

Pilot study

0.0%

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

Ceftriaxone resistance in Salmonella serotype Heidelberg, 1996-2012*

*2012 human data are preliminary; only 10 ground turkey isolates were tested in 2009 and 11 retail chicken isolates in 2002 and 2011

0% 3%

32%

Salmonella Heidelberg in QuébecCeftiofur resistance – 2003-2008

Cft R S. Heidelbergwas common inpoultry meat, butwas not found in beef or pork

2005-2006:Poultry industryin Québecvoluntarily halteduse of ceftiofurin eggs

Dutil et al. 2010 EID 16: 48-54

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

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 45:2716-2722Folster et al 2012 FPD19:638-645

Salmonella Typhi

Shigella

Ciprofloxacin resistance

*preliminary data

2011: resistance to Amp 34%, Tet 41%, TMP-SXT 67% Reduced susceptibility to azithromycin:

• 3.1% in 2011 and 4.3%* in 2012

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

Challenges in other parts of the world

WHO Campylobacter Consultation 2013 2013 Kotloff Lancet; 2008 Gordon CID; 2011 Su EID;

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 13:652-679Wasyl 2012 Food Research Int 45:958-961

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

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

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

Addressing the public health concern about resistant foodborne zoonotic infections

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

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

Antimicrobial resistance: www.cdc.gov/drugresistance/index.html

Our Programs:NARMS: www.cdc.gov/NARMS FoodNet: www.cdc.gov/foodnetPulseNet: www.cdc.gov/pulsenetFoodCORE: www.cdc.gov/ncezid/dfwed/orpb/foodcore/index.html

Specific pathogens:E. coli: www.cdc.gov/ecoliSalmonella: www.cdc.gov/salmonellaListeria: www.cdc.gov/listeria

Multistate foodborne outbreaks:www.cdc.gov/outbreaknet/outbreaks.html

General information about foodborne diseases:www.cdc.gov/foodsafetywww.foodsafety.gov

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