Norwegian policies to address antimicrobial resistance

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Norwegian policies to address antimicrobial resistance 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

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

Low AMR in Norway 3rd generation cephalosporin (R+I) Klebsiella pneumoniae 2005 2006 2008 2010 2012 2014 Ref: ECDC, EARS-Net

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 ESBL KARBA. 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

Tonnes antibacterials Total usage of antibiotics in Norway, in tonnes active substance. Note that it is not accounted for the human or animal population 60 50 40 30 20 10 0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 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)

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.

DDD/1,000 inhabitants/day Goal 1 and 4. Reduction of antibiotic usage 25 J01, antibacterials for systemic use Antibiotics for respiratory infections 20 15 10 Goal 30% red. 5 Goal 20% red. 0 2012 2013 2014 2015 2016 2017 2018 2019 2020

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*

% change 2012-2016 National action plan - Goal reduction of antibiotic usage hospitals 10% 5% 0% -5% -10% -15% -20% -25% -30% Target National Action Plan: 30% reduction, 2012-2020 -35% Helse Møre og Romsdal HF Sykehuset Innlandet HF Sørlandet Sykehus HF Oslo Universitetssykehus HF Akershus Universitetssykehus HF Helse Nord-Trøndelag HF Vestre Viken HF Helse Bergen HF Norwegian hospitals (total) Sykehuset Telemark HF Universitetssykehuset Nord- St. Olavs Hospital HF Diakonhjemmet Sykehus Lovisenberg Diakonale Sykehus Nordlandssykehuset HF Helse Førde HF Finnmarkssykehuset HF Helse Stavanger HF Helse Fonna HF Helgelandssykehuset HF Sykehuset Østfold HF Haraldsplass Diakonale Sykehus Sykehuset i Vestfold HF Sunnaas Sykehus HF

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/antibiotikar esistens-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 ESBL occurrence (%) Broiler Broiler meat Broiler Broiler meat Broiler Broiler meat ESBL occurrence (%) 2016 data show significant reduction in ESBL occurrence in broilers

Usage in food producing animals, including horses, in 29 EU/EEA countries in 2014 Norway among EU/EEA countries with lowest usage

kg Usage (kg) of antibiotics in food producing 6000 terrestrial animals (includes horses) Target: The usage of antibiotics in food producing terrestrial animals should be reduced by at least 10 percent compared to 2013 5000 4000 3000 2000 Measured in kg - a reduction of 3.6% from 2013-2016 is observed 1000 0 2013 2014 2015 2016 Penicillins Sulfonamides Trimethoprim Aminoglycosides Macrolides Fluoroquinolones Pleuromutilines Tetracyclines

mg / PCU Usage (mg/pcu) of antibiotics in food producing terrestrial animals 12 Target: The usage of antibiotics in food producing terrestrial animals should be reduced by at least 10 percent compared to 2013 10 8 6 4 10.4 10.1 10.3 10.2 Measure in mg/pcu - a reduction of 1.9% from 2013-2016 is observed 2 0 2013 2014 2015 2016 PCU= population correction unit (EU/EMA standard)

1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 kg Historical usage of antibiotics in food Target set by the industry: 25% reduction in 5 years with 1995 as reference year producing terrestrial animals 10000 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 Food producing animals (terrestrial) Usage relatively stable in the period 2013 to 2016 Of note: from 1995 to 2012 a 39 % reduction was observed Penicillins Sulfonamides Trimethoprim* Aminoglycosides Macrolides Fluoroquinolones Pleuromutilines Tetracyclines

mg/pcu Usage of antibiotics in farmed fish 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 0.8 0.7 0.6 0.5 0.4 0.3 0.7 For the period 2004-2014 average usage was 1.1 mg/pcu 0.2 0.4 0.1 0.2 0.2 0.0 2013 2014 2015 2016

1981 1982 1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 Tonnes 1000 tonnes Historical usage of antibiotics in farmed fish Antibacterials sold (tonnes) Biomass slaughtered farmed fish (1000 tonnes) 50 45 40 99% reduction in usage, in tonnes, from 1981 to 2016 1400 1200 35 30 25 20 15 10 5 1000 800 600 400 200 0 0

kg 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 600 500 400 300 200 100 0 2013 2014 2015 2016 Penicillins Sulfonamides+trimethoprim Lincosamides Fluoroquinolones 1st gen. cephalosporins 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

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

Studies of environmental factors 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

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

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

Vaccine R&D - Norway on of the founding partners of CEPI World Economic Forum, Davos 19 Jan 27/09/2017 36

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