Frode Forland, Specialist Director, Division of Infectious Control and Environmental Health, Norwegian Institute of Public Health

Karianne Johansen, Senior advisor, Division of Infectious Control and Environmental Health, Norwegian Institute of Public Health

Kari Grave, Senior scientist, Norwegian Veterinary Institute

Anne Margrete Urdahl, Senior scientist, Norwegian Veterinary Institute

Norwegian policies to address antimicrobial resistance

TATFAR Scope

• Appropriate therapeutic use of antimicrobial drugs in humans and animals

• Prevention of drug-resistant infections

• Strategies for improving the pipeline of new antimicrobial drugs and diagnostic devices, and maintaining existing drugs on the market

3rd generation cephalosporin (R+I) Klebsiella pneumoniae

Ref: ECDC, EARS-Net

2005 2006 2008

2010 2012 2014

Low AMR in Norway

… but AMR is increasing

Percentage ESBL-positive E. coli og Klebsiella spp blod and urine (NORM/NORM-VET, 2016) Source. NORM/NORM-VET

Number of persons yearly listed with one more gram-negative bacteria with ESBLKARBA. Source: MSIS (5).

The Norwegian Governmental Strategy

• Multisectorial strategy signed by 4 ministers

• Aims to examine in a holistic way

– the usage of antibiotics and other drivers of resistance

– the development and spread of resistance among humans, animals, in food and in the natural environment

• Provides guidance for joint efforts against antibiotic resistance

Overarching goals for the period 2015–2020

1. Reduce the total usage of antibiotics

2. More appropriate use of antibiotics

3. Improved knowledge of what drives the development and spread of antibiotic resistance

4. Be a driver in international and normative work to improve access, responsible use, and development of new antibiotics, vaccines and better diagnostic tools

0

10

20

30

40

50

60

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

To

nn

es a

nti

bac

teri

als

Methenamine

Other antibacterials

Tetracyclines

Trimethoprim

Sulfonamides

Trimethoprim + sulfonamide

Quinolones

Macrolides

Lincosamides

Cephalosporins

Aminoglycosides (AG)

Penicillin + AG + sulfonamide

Penicillin + AG

Penicillins

↑ Human use

↓ Animal use

(Farmed fish in black)

Total usage of antibiotics in Norway, in tonnes active substance. Note that it is not accounted for the human or animal population

Sector specific goals – Human sector

1. Antibiotic usage in the total inhabitants should be reduced by 30 percent, measured in DDD/1000 inhabitants/day, as compared with 2012

2. Norway should be one of the three European countries with lowest usage of antibiotics in humans, measured in DDD/1000 inhabitants/day

3. Prescription of antibiotics should be reduced from an average today of 450 prescriptions per 1000 inhabitants per year to 250 prescriptions per 1000 inhabitants per year

4. Prescription of antibiotics for respiratory infections should be reduced by 20 percent, measured in DDD/1000 inhabitants/day, compared to 2012

5. Studies will be carried out on the burden of disease as a consequence of antibiotic resistance, as a consequence of possibly too little antibiotic use, and the effect of infection control measures.

Goal 1 and 4. Reduction of antibiotic usage

0

5

10

15

20

25

2012 2013 2014 2015 2016 2017 2018 2019 2020

DD

D/1

,00

0 i

nh

abit

ants

/day

J01, antibacterials for systemic use Antibiotics for respiratory infections

Goal

30%

red.

Goal

20%

red.

Low consumption of antibiotics in Norway

Consumption of antibiotics for systemic use in the community by antibiotic group in 30 EU/EEA countries, 2015 (expressed in DDD per 1 000 inhabitants and per day)

• Consumption of antibiotics for systemic use in the hospital sector by antibiotic group in 20 EU/EEA countries, 2015*

National action plan - Goal reduction of antibiotic usage hospitals

-35%

-30%

-25%

-20%

-15%

-10%

-5%

0%

5%

10%

Sunnaas S

yk

ehus H

F

Sykeh

uset i V

estfold

HF

Harald

splass D

iakonale S

ykeh

us

Sykeh

uset Ø

stfold

HF

Helg

elandssy

keh

uset H

F

Helse F

onna H

F

Helse S

tavan

ger H

F

Fin

nm

arkssy

keh

uset H

F

Helse F

ørd

e HF

Nord

landssy

keh

uset H

F

Lovisen

berg

Diak

onale S

ykeh

us

Diak

onhjem

met S

ykeh

us

St. O

lavs H

osp

ital HF

Univ

ersitetssykeh

uset N

ord

-…

Sykeh

uset T

elemark

HF

Norw

egian

hosp

itals (total)

Helse B

ergen

HF

Vestre V

iken

HF

Helse N

ord

-Trø

ndelag

HF

Akersh

us U

niv

ersitetssykeh

us H

F

Oslo

Univ

ersitetssykeh

us H

F

Sørlan

det S

ykeh

us H

F

Sykeh

uset In

nlan

det H

F

Helse M

øre o

g R

om

sdal H

F%

chan

ge

2012

-2016

Target National Action Plan: 30% reduction, 2012-2020

Main goals - Food producing and companion animals

1. Mapping of reservoirs of antibiotic resistant bacteria will be carried out in the most relevant animal populations and plants important for food safety

2. LA-MRSA should not be established in the Norwegian pig population

3. ESBL in the Norwegian poultry-production should be reduced to a minimum

4. The usage of antibiotics in food producing terrestrial animals should be reduced by at least 10 percent compared to 2013

5. Total antibiotic usage in fish farming in 2020 should be at the same or lower levels than for the period 2004-2014, measured in total kilograms of antibiotics

6. The usage of antibiotics in companion animals should be reduced by at least 30 percent compared to 2013

AMR in the animal sector

• AMR in Norwegian animals, feed and food is in general very low

• Note: 2016 data similar to 2014 data shown in EFSA figure

• More national data available on https://www.vetinst.no/overvaking/antibiotikaresistens-norm-vet

Mapping of reservoirs for AMR

• Surveys additional to requirements given through the EU regulation

• Building knowledge step by step, year by year

• Focus last years and for 2017 – Ready to eat vegetables and herbs

– Cheese, both pasteurized and unpasteurized, imported and domestic

– Shellfish, both imported and domestic

– Wildlife – red fox and wild birds (covering environment)

LA- MRSA in swine

• Surveillance of MRSA in swine – search and destroy strategy – risk based

• Positive findings followed by depopulation, washing and disinfection procedures, repopulation with MRSA free pigs

LA-MRSA in swine – one health perspectives

• Humans are main source for introduction to Norwegian swine herds

• Focus on preventing introduction through testing of humans

ESBL in broilers

• 2016 data show significant reduction in ESBL occurrence in broilers

ESBL occurrence (%)

ESBL occurrence (%)

Broiler Broiler Broiler Broiler meat Broiler meat Broiler meat

Usage in food producing animals, including horses, in 29 EU/EEA countries in 2014

Norway among EU/EEA countries with lowest usage

Usage (kg) of antibiotics in food producing terrestrial animals (includes horses)

0

1000

2000

3000

4000

5000

6000

2013 2014 2015 2016

Penicillins Sulfonamides Trimethoprim

Aminoglycosides Macrolides Fluoroquinolones

Pleuromutilines Tetracyclines

kg

Measured in kg - a reduction of 3.6% from 2013-2016 is observed

Target: The usage of antibiotics in food producing terrestrial animals should be reduced by at least 10 percent compared to 2013

Usage (mg/PCU) of antibiotics in food producing terrestrial animals

Measure in mg/PCU - a reduction of 1.9% from 2013-2016 is observed

PCU= population correction unit (EU/EMA standard)

10.4 10.1 10.3 10.2

0

2

4

6

8

10

12

2013 2014 2015 2016

mg /

PC

U

Target: The usage of antibiotics in food producing terrestrial animals should be reduced by at least 10 percent compared to 2013

Historical usage of antibiotics in food producing terrestrial animals

• Usage relatively stable in the period 2013 to 2016

• Of note: from 1995 to 2012 a 39 % reduction was observed

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

199

3

199

4

199

5

199

6

199

7

199

8

199

9

200

0

200

1

200

2

200

3

200

4

200

5

200

6

200

7

200

8

200

9

201

0

201

1

201

2

201

3

201

4

201

5

201

6Penicillins Sulfonamides Trimethoprim* Aminoglycosides

Macrolides Fluoroquinolones Pleuromutilines Tetracyclines

Food producing animals (terrestrial)

kg

Target set by the industry: 25% reduction in 5 years with 1995 as reference year

Usage of antibiotics in farmed fish

For the period 2004 - 2014 average usage was 1.1 mg/PCU

Target: Total antibiotic usage in fish farming in 2020 should be at the same or lower levels than for the period 2004-2014, measured in total kilograms of antibiotics

0.7

0.4

0.2 0.2

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

2013 2014 2015 2016

mg/

PC

U

Historical usage of antibiotics in farmed fish

0

200

400

600

800

1000

1200

1400

0

5

10

15

20

25

30

35

40

45

50

198

1

198

2

198

3

198

4

198

5

198

6

198

7

198

8

198

9

199

0

199

1

199

2

199

3

199

4

199

5

199

6

199

7

199

8

199

9

200

0

200

1

200

2

200

3

200

4

200

5

200

6

200

7

200

8

200

9

201

0

201

1

201

2

201

3

201

4

201

5

201

6

Antibacterials sold (tonnes) Biomass slaughtered farmed fish (1000 tonnes)

Ton

nes

99% reduction in usage, in tonnes, from 1981 to 2016

10

00

to

nn

es

Usage of antibiotics in companion animals

Target: The usage of antibiotics in companion animals should be reduced by at least 30 percent compared to 2013

• For the period 2013 - 2016 a reduction of 24% in kg’s sold of antibacterials marketed for companion animals only is observed

• Note: Usage of human antibacterials is not included 0

100

200

300

400

500

600

2013 2014 2015 2016

Penicillins Sulfonamides+trimethoprim

Lincosamides Fluoroquinolones

1st gen. cephalosporins

kg

Concluding remarks - animals

• With regard to fulfilling the sector specific goals on ESBL and LA-MRSA, the results are so far promising

• The results shows that in terms of usage in animals, Norway is moving in the right direction

Sector specific goals – Climate and Environment

1. Mapping of antibiotic resistant bacteria will be carried out in representative environments and selected organisms in animals, water and soil with varying degrees of exposure to antibiotics

2. Studies will be initiated to explore the effect in nature of other drivers of resistance, including disinfectants, biocides and heavy metals

• The Norwegian Environment Agency has launching several studies of environmental factors that can contribute to of development of AMR

• Wildlife – red fox and wild birds (covering environmental aspects of action plan)

• Heavy metals and AMR

• Mapping of antibiotic resistant bacteria in aquatic environment

Studies of environmental factors

Goal: A driver in international and normative work to improve access, responsible use, and development of new antibiotics, vaccines and better diagnostic tools

Suggested international AMR policy actions

• Strengthening surveillance and monitoring systems in the community and hospitals

• Fostering research and development of new antimicrobial therapies, including improved biosecurity measures in agriculture

• Need for both “push” and “pull” mechanisms

• Access and sustainable use are integral

• Global collaboration and financing necessary

• Enhancing coordination between countries to develop a true global action plan to tackle AMR

• Adopt a broader ‘one-health’ approach covering human health, agriculture and the environment

Norwegian activities

• Co-lead DRIVE AB WP2Creation and testing of new economic models

• Joint Action on Antimicrobial Resistance & Healthcare-Associated Infections “EU-JAMRAI” – WP7: Appropriate Use of Antimicrobials in Human

and Animals

– WP9: Prioritizing & Implementing Research and Innovation for Public Health Needs

• The Global Antimicrobial Resistance (AMR) Collaboration Hub co-ordinate efforts to

invigorate antimicrobial research

encourage global involvement and investment

• The scope of work all stages of the

antimicrobial development pipeline

vaccines, alternative therapies and new diagnostic tools

34

G20 - calling for an international collaboration hub for AMR R&D

27/09/2017 36

Vaccine R&D - Norway on of the founding partners of CEPI World Economic Forum, Davos 19 Jan

What is CEPI?

• CEPI is a partnership of public, private, philanthropic and civil society organisations

• CEPI will stimulate, finance and coordinate vaccine development

• against priority threats,

• particularly when development is unlikely to occur through market incentives alone

• CEPI’s Initial Target Diseases

• Starting point: WHO’s list of priority pathogens defined by the WHO R&D Blueprint

MERS

Lassa

Nipah