This document discusses antimicrobial resistance and antibiotic consumption in Denmark. It provides an overview of antibiotic use and resistance trends in Denmark, including: 1) Decreasing antibiotic consumption in pigs and overall in primary healthcare, though consumption is still increasing in hospitals. 2) National surveillance of resistant bacteria finds increasing resistance in E. coli and K. pneumoniae from invasive infections. MRSA rates remain low at 1.6% while carbapenem-resistant Enterobacteriaceae are an emerging issue. 3) Denmark has national strategies and guidelines to continue reducing antibiotic use in animals and humans to tackle the development of antimicrobial resistance.

1. Antimicrobial resistance
and
consumption
Anne Kjerulf
National Center for Infection Control
Statens Serum Institut

2. AGENDA
Antibiotic resistance – why?
The Danish experience
- Antibiotic consumption in Denmark
- Multidrug resistant microorganisms
• Methicillin-resistant Staphylococcus aureus (MRSA)
• Carbapenemase-producing organisms (CPO)
• Vancomycin-resistant enterococci (VRE)
How can we tackle AMR?
- Antibiotic stewardship (not included here)
- Guidelines – universal precautions and isolation
precautions
- Specific national guidelines for MRSA and CPO
AMR and antibiotic consumption, St Petersburg December 2019 2

3. ANTIBIOTIC RESISTANCE – WHY?
Wellknown bacteria like E.coli and S. aureus become
more and more resistant against the antimicrobial
agents that we use for treatment of infections
Why? Increasing consumption of antimicrobial agents
in the recent years – both animals and human beings
globally and on the national level
Broad-spectrum antibiotics select for resistance,
especially cephalosporins, fluoroquinolones and
carbapenems
AMR and antibiotic consumption, St Petersburg December 2019 3

4. Denmark
- 44.000 sq km
- 5,5 million inhabitants
PIGS: 26 million pigs slaughtered/year.
Worlds largest exporter of pork meat (export to EU, Japan,
Russia, USA)
POULTRY: 130 million broilers slaughtered /year
(export to EU and the Middle East)
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5. CONSUMPTION OF ANTIMICROBIAL AGENTS
IN DENMARK
Antimicrobial Resistant
Bacteria
AMR and antibiotic consumption, St Petersburg December 2019 5

6. DANMAP
DANISH
INTEGRATED
ANTIMICROBIAL
MONITORING AND
RESEARCH
PROGRAMME
 Established in 1995
 Cooperation with:
- National Food Institute, DTU
- National Veterinary Institute, DTU
- Danish Medicine Agency
- Statens Serum Institut
 Yearly rapport since 1997
http://www.danmap.org
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7. Isolates
Samples
National Food
Institute, DTU
Data
DANMAP
Statens Serum Institut
Data
Danish Medicine
Agency
Data
Data
Private
Laboratories
Regional hospital
laboratories
Diagnostic
submission
Samples
Samples
Isolates /
data
Regional food
control laboratories
Slaughter plants
Veterinary practice
Samples
General practice
VetStat, National
Veterinary Institute
DANMAP –
data flow
Danish Veterinary and
Food Administation
Data
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8. CONSUMPTION OF ANTIMICROBIAL AGENTS IN DENMARK
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9. CONSUMPTION IN PIGS – DECREASE IN TREATMENTS
0
20
40
60
80
100
120
140
09 10 11 12 13 14 15 16 17 18
Sows and piglets Weaners Finishers All age groups, adjusted
DAPD(DADDper1000animalsperday)
0
1
2
3
4
5
6
7
8
9
10
11
09 10 11 12 13 14 15 16 17 18
DAPD(DADDper1000animalsperday) Aminoglycosides Amphenicols
Lincosamides(a) Macrolides
Penicillin's, b-lactamase sensitive Penicillin's, others(b)
Pleuromutilins Sulfonamides and trimethoprim
Tetracyclines
All age groups, adjusted
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10. TOTAL CONSUMPTION OF ANTIMICROBIAL AGENTS IN HUMANS
Consumption is highest in primary health care (90%) but decreasing
Consumption is still increasing in the hospitals
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11. TOTAL CONSUMPTION IN EACH OF THE 5 REGIONS
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12. CONSUMPTION IN PRIMARY HEALTH CARE
Figure 5.3 Consumption of leading antimicrobial groups for systemic use in primary health care, DID, Denmark
DANMAP 2018
Data used for this figure is based on total sales in Denmark (individuals and clinics)
ATC numbers stem from the 2019 edition of the Anatomical Therapeutic Chemical (ATC) classification system
0
1
2
3
4
5
6
2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
DDDper1000inhabitant-day
Beta-lactamase sensitive
penicillins (J01CE)
Penicillins with extended
specrum (J01CA)
Macrolides (J01FA)
Tetracyclines (J01AA)
Beta-lactamase resistant
penicillins (J01CF)
Fluoroquinolones (J01MA)
Comb. of penicillins, incl.
beta-lactamase inhibitors
(J01CR)
Penicillins compromise 2/3 of the total consumption in primary health care – but compared to earlier we see an
increase in broad-spectrum penicillins and a decrease in small-spectrum penicillins
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13. CONSUMPTION IN HOSPITALS
Penicillins compromise 54% of the total consumption
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14. CONSUMPTION IN HOSPITALS IN THE NORDIC COUNTRIES, 2017
Vidar Möller, Folkhälsomyndigheten, 2018
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15. CONSUMPTION IN HOSPITALS IN EUROPE
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16. NATIONAL STRATEGIES IN DENMARK, 2017
Target areas:
Continued reduction in use of antimicrobial agents to animals
Continued improvement of animal welfare
Increased focus on education and knowledge sharing
Three concrete goals:
1) Reduction in the total consumption in primary health care
2) Penicillin V shall continue to be the most used antimicrobial
agent
3) Reduction in consumption of the critical important
antimicrobial agents in hospitals
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17. QUESTIONS
What are the Russian experiences with consumption of antimicrobial
agents?
- In animals? The same problem with pigs?
- In hospitals?
- In primary health care?
Prescription of antimicrobial agents or counter sale?
Do the doctors earn money on the prescriptions?
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18. ANTIBIOTIC RESISTANCE IN DENMARK
Antimicrobial Resistant
Bacteria
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19. National surveillance
Full test
rapport Data
Blood and spinal fluid:
E. coli, K. pneumoniae
Enterococci,
P. aeruginosa,
Acinetobacter
Urine samples from hospitals and
primary health care:
E. coli, K. pneumoniae
First isolate per patient per year
Susceptibility testing data
1. Data based
Rutine diagnostics from all 10 departments of clinical microbiology in
Denmark
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20. Total number of bacteremia
47%
19%
7%
11%
7%
5%
4%
E. coli S. aureus S. pneumoniae
K. pneumoniae E. faecium E. faecalis
P. aeruginosa
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21. Bacteremia per 100.000 inhabitants
51%
64%
-20%
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22. S. aureus, invasive isolates
2018: 2.276 cases with S. aureus bacteremia (2009: 1.466 cases)
MRSA 1,6%
EARS-Net 2017, MRSA: 16,9% (0% - 57,1%)
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23. MRSA IN DENMARK
2018: 3669 new cases
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24. MRSA, EPIDEMIOLOGY
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25. E. coli, invasive isolates
EARS-Net 2017, multiresistente E. coli: 6,3% (1,5% - 24,9%)
EARS-Net 2017, 3. gen cephalosporin R E. coli: 14,9% (5,9% - 41,3%)
EARS-Net 2017, fluoroquinolon R E. coli: 25,7% (11,6% - 44,9%)
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26. K. pneumoniae, invasive isolates
Figure 8.6 K. pneumoniae. Resistance (%) in
invasive isolates from humans, Denmark
EARS-Net 2017, multiresistant K. pneumoniae: 20,5% (0% - 57,1%)
EARS-Net 2017, 3. gen cephalosporine R K. pneumoniae: 31,2% (4,6% -
76,3%)
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27. CPE, clinical and screening isolates
2018: 156 CPE from 141 patients,
15 fra blood
2017: 104 CPE from 96 patients,
5 from blood
2008-2013: 31 CPE
0
20
40
60
80
100
120
140
160
180
2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
OXA-48-group NDM NDM/OXA-48-group KPC VIM
More than one isolate was included from the same patient, if the isolates belonged to different bacterial species
and/or harboured different carbapenemases
Figure 8.13 Numbers of carbapenemase-producing Enterobacterales
(CPE), 2008-2018, Denmark
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28. Enterococci, invasive isolates
EARS-Net 2017, VRE: 14,9% (0% - 43,9%)
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29. VRE, clinical isolates
Figure 8.14 Numbers of Enterococcus faecium and Enterococcus faecalis isolates carrying vanA and vanB genes from clinical samples submitted to
SSI 2009-2018 supplemented with data obtained from MiBa from 2016-2018, Denmark
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30. QUESTIONS
What are the Russian experiences with surveillance of AMR?
- In hospitals?
- In primary health care?
Where do the AMR come from? And what is the biggest problem?
Are there national or regional reference laboratories in Russia?
What methods are used for typing of AMR?
- Phenotype
- Genotype
- WGS
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31. QUESTIONS
What are the Russian experiences with guidelines for infection prevention
and control?
- Are there common national guidelines?
- Are there regional/local guidelines?
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32. THANKS FOR ATTENTION – ANY QUESTIONS?
33AMR and antibiotic consumption, St Petersburg December 2019