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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