Udbredelse og betydning af resistente bakterier: Fokus på spredning fra dyr til mennesker

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1 Udbredelse og betydning af resistente bakterier: Fokus på spredning fra dyr til mennesker Frank M. Aarestrup

2 Importance of the food animal reservoir for human health Different estimates ranging from Almost zero (AHI and IFAH) 1,518 extra deaths and an associated increase of 67,236 days of hospital admissions in Europe as a result of cephalosporin use in chickens alone (Collignon et al. 2013) 2 7 October 2015

3 Spread Veterinarian Hospital Population Travel Adoption Turist Abbatoirs Food products Farmer Production animals Animal waste Environment

4 Hvorfor bruger vi antibiotika til dyr Terapi Behandling af synligt syge dyr Meta-fylakse Behandling af grupper af dyr som må formodes at være smittede Profylakse Rutinemæssig brug af antibiotika på bestemte tidspunkter Vækstfremmer Hele tiden i foderet for at fremme væksten 4 7 October 2015

5 Treatment of infection in Lung Selection of Resistance in gut

6 Significant increase But cephalosporins have not been used for danish broilers in 10 years

7 The Danish broiler production ESBL ESBL ESBL ESBL Day-old Grand Parant Grandparant flocks Day-old Parant Parant flock and broiler flocks Cephalosporin usage No Cephalosporin usage No Cephalosporin usage Usage in one country can affect resistance in another country

8 The old zoonosis Antimicrobial resistant Salmonella (DT104) Campylobacter (FQ and macrolide resistant)

9 The new zoonosis Antimicrobial resistant: Enterococci E. coli S. aureus C. difficile Resistance genes

10 Evidence over time Introduction of apramycin, streptothricin and fluoroquinolones in animals prior to use in humans were followed by emergence in humans Removal of tetracyclines and avoparcin for animals followed by reduction in resistance in humans 10

11 Emerg Infect Dis Jan;16(1):48-54 Prevalence of ceftiofur resistance (moving average of the current quarter and the previous 211 quarters) DTU Food, among Technical retail University chicken of Denmark Escherichia coli, and retail chicken and human 7 clinical October 2015 Salmonella enterica serovar Heidelberg isolates during in Québec, Canada.

12 Extended spectrum β lactamase producing and AmpC producing Escherichia coli from livestock and companion animals, and their putative impact on public health: a global perspective Clinical Microbiology and Infection Volume 18, Issue 7, pages , 23 APR 2012 DOI: /j x

13 13

14 14 7 October 2015

15 Phylogeny of clones 15 7 October 2015

16 Phylogeny of plasmids 16 7 October 2015

17 De Been et al. conclusions Recent transfer between farmers and pigs No evidence for recent transfer between chickens and humans Recent dissemination of plasmids between E. coli from chickens and humans 17 7 October 2015

18 18 7 October 2015

19 19 7 October 2015

20 A swine B 1.E3 cattle poultry DK_ _cattle_ _farm_D16 DK_ _turkey_ DK_ _turkey_ DK_ _cattle_ _farm_D19 DK_ _cattle_ _farm_D19 DK_ _pig_ _farm_D13 DK_ _pig_ _farm_D31 DK_ _swine_ _farm_D32 DK_ _swine_ _farm_D42 DK_ _swine_ _farm_D47 DK_ _2_swine_ _farm_D41 DK_ _3_swine_ _farm_D42 DK_ _1_swine_ _farm_D41 DK_ _swine_ _farm_D42 DK_ _swine_ _farm_D32 DK_ _1_swine_ _farm_D42 DK_ _swine_ _farm_D42 DK_ _3_swine_ _farm_D42 DK_ _swine_ _farm_D42 DK_ _swine_ _farm_D42 DK_ _swine_ _farm_D32 DK_ _chicken_ _farm_D34 DK_ _chicken_ _farm_D34 DK_ _chicken_ _farm_D34 DK_ _chicken_ _farm_D34 DK_ _pig_ _farm_D45 DK_ _swine_ _farm_D37 DK_ _swine_ _farm_D22 DK_ _cattle_ _D30 DK_ _pig_ _farm_D28 DK_ _swine_ _farm_D44 DK_ _pig_ _farm_D26 DK_ _pig_ _farm_D5 DK_ _cattle_ _farm_D23 DK_ _cattle_ _farm_D24 DK_ _pig_ _farm_D40 DK_ _swine_ _farm_D39 DK_ _swine_ _farm_D39 DK_ _pig_ _farm_D39 DK_ _1_swine_ _farm_D39 DK_ _3_swine_ _farm_D39 DK_ _swine_ _farm_D39 DK_ _pig_ _farm_D8 DK_ _pig_ _farm_D1 DK_ _swine_ _farm_D9 DK_ _2_swine_ _farm_D9 DK_ _1_swine_ _farm_D9 DK_ _swine_ _farm_D9 DK_ _pig_ _farm_D20 DK_ _swine_ _farm_D3 DK_ _chicken_ _farm_D11 DK_ _swine_ _farm_D43 DK_ _swine_ _farm_D6 DK_ _swine_ _farm_D33 DK_ _swine_ _farm_D35 DK_ _cattle_ _farm_D21 DK_ _swine_ _farm_D10 DK_ _swine_ _farm_D36 DK_ _calf_ _farm_D14 DK_ _cattle_ _farm_D14 DK_ _cattle_ _farm_D17 DK_ _cattle_ _farm_D15 DK_ _swine_ _farm_D46 DK_ _cattle_ _farm_D29 DK_ _cattle_ _farm_D29 DK_ _pig_ _farm_D12 DK_ _6_swine_ _farm_D38 DK_ _swine_ _farm_D38 DK_ _4_swine_ _farm_D38 DK_ _swine_ _farm_D38 DK_ _3_swine_ _farm_D38 DK_ _cattle_ _farm_D27 DK_ _cattle_ _farm_D27 DK_ _cattle_ _farm_D25 DK_ _7_swine_ _farm_D38 C Effective population size 1.E2 1.E1 1.E0 D D46 D29 D1 D42 D28 D45 D44 D33 D24 D26 D41 D23 D25 D3 D20 D21 D34 D38 D9 D18 D19 D17 D2 D4 D7 D37 D22 D14 D11 D16 D15 D40 D35 D27 D12 D43 D32 D8 D10 D36 D47 Time Time D31 D5 D D October 2015

21 Formodet spredning af MRSA i den danske svineproduktion Avlstoppen Avls/produktion Direkte spredning Landmænd Produktion Indirekte (miljø, kød, etc.)? befolkningen

22 R Pseudomonas aeruginosa R Acinetobacter baumannii MRSA R E. coli VRE R Salm. R E. coli R Strep. pneumoniae R Haem. influenzae R S. aureus R Camp. R E. coli VRE R S. aureus

23 Horizontal transfer of resistance genes R Pseudomonas aeruginosa R Acinetobacter baumannii MRSA R Salm. R Camp. R E. coli VRE C. diff. R E. coli R Strep. pneumoniae R Haem. influenzae R E. coli VRE C. diff. MRSA & R S. aureus

24 Selection and Spread Abbatoirs Food products Population Production animals Prevention of diseases Correct diagnostics and treatment Reduced use Critical important antibiotics Improved hygieine Hygieine Choice of product

25 Antimicrobial consumption and millions of heads of pigs produced in Denmark from 1994 to Frank M. Aarestrup Phil. Trans. R. Soc. B 2015;370: by The Royal Society

26 Targeted control Canberra and Copenhagen Expert Reports Most critical : - Quinolones - 3 rd gen. cephalosporins - Macrolides

27 Data on production characteristics for piglet mortality (per cent; grey triangles) and mean number of pigs produced per sow per year (black diamonds) (a), average daily gain (ADG, grey triangles) and mortality rate (black squares) in weaning pigs (b), and a... Frank M. Aarestrup Phil. Trans. R. Soc. B 2015;370: by The Royal Society

28 Berge et al. 2009, J. dairy sci. Two times more diarrhea in calves routinely treated with antibiotics 28 7 October 2015

29 Why is it so difficult to reduce consumption Pharmaceutical lobby Treatment -Direct effect saves life -Easy to show -Easy to quantify -Anima welfare Production -Direct economy -Easy management tool -Me, me me Restriction and human health - In-direct - Difficult to quantify - No direct economical interest - Low term effects - Perhaps effects - Others (not me)

30 Conclusions Total antimicrobial consumption can be reduced without compromising productivity Specific drugs can be almost or entirely removed This will led to reduction in resistance Use in one country affects other countries Probably easier with larger reductions in most other countries Still a lack of data quantifying the livestock contribution

31 Despite 20 years of asking we still need Integrated, long-term surveillance with optimal sampling in settings where interventions occur Harmonised characterisation (real-time) Exchange of data and strains to allow comparisons Data on associations between antimicrobial use, animal health, productivity and economy

32 Overvågningspyramiden Reported to health unit Culture-confirmed case Lab tests for organism Specimen obtained Person seeks care Person becomes ill Population exposures

33 Farm surveillance based on manure

34 Whole community sequencing Associations between consumption (ADD) and tetracycline resistance Preliminary data

35 Sci. Rep. in press

36

37 A suggestion A single large scale cohort study Sampling food and humans sources Analysing using novel technologies

38 Next logical step Platform

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