National Action Plan on Antimicrobial Resistance in Humans

1216 Copenhagen K, Denmark Tel. +45 72 26 90 00 ISBN 978-87-7601-446-9 (web) ISBN 978-87-7601-447-6 (print) Design BGRAPHIC Photos iStock Danish Health Authority pages 13 and 17 Printing OnPrint The publication is available on the website of the Ministry of the Interior and Health of Denmark: www.ism.dk Table of contents Foreword ....................................................................................................................... 4 The stories of Peter, Malene and Thorvald ..................................................... 7 The threat of antimicrobial resistance ............................................................ 8 Antimicrobial resistance from a One Health perspective....................... 9 Priority area 1: Antimicrobial stewardship...................................................... 14 Priority area 2: Access to antimicrobials ........................................................ 18 Priority area 3: Infection prevention and control......................................... 20 Priority area 4: International engagement .................................................... 22 Cross-cutting initiatives ........................................................................................ 24 Financial overview of the national action plan on antimicrobial resistance in humans .......................................................... 25 Appendix: Overview of objectives and indicators in the national action plan on antimicrobial resistance in humans ............................................... 26 Foreword Antimicrobials, and especially antibiotics, Fortunately, tireless efforts are already save lives every day. They save lives by underway to prevent the development of treating common pneumonia which, less resistance, even if many of us are unaware than 100 years ago, would have been a of it in our everyday lives. It is the general death sentence for many. They save lives practitioner who makes a conscious effort by protecting the most vulnerable members to prescribe antibiotics only when needed. of our society, whose immune systems cannot The microbiologist who analyses samples defend themselves. They save lives by and keeps hospital colleagues up to date on enabling us to carry out complex procedures the latest clinical knowledge. The social and such as organ transplantation. healthcare assistant at the nursing home who protects residents from infection through But we cannot take for granted that the meticulous attention to hygiene. future will look the same. Microorganisms are in a constant race with medical science, The major day-to-day effort in Denmark has developing defence mechanisms that make been supported by the 2017 National action them resistant to antimicrobials. This is known plan on antibiotics for humans, which outlined as antimicrobial resistance, or simply AMR. three ambitious goals to reduce antibiotic Each time we use an antimicrobial drug, consumption in Denmark. The action plan we fuel the risk of developing resistance. has served as an important point of reference We therefore have to use them with particular in the fight against antibiotic resistance and care. has contributed to Denmark’s strong standing today compared to many other countries Failing to do so could have insurmountable around the world. consequences. In a world without effective antimicrobials, doctors would be unable But our work is far from over. We are fighting to treat patients for commonly occurring a global trend. Resistance is spreading more infections. A patient with osteoarthritis would and more across the globe. In many places not be able to receive a hip replacement around the world, common infections have without putting themselves at risk. A person once again become life-threatening. The suffering from chronic illness would not be World Health Organization (WHO) estimates able to hug their grandchildren without that, by 2050, AMR could be responsible for fearing a potentially life-threatening infection. more deaths worldwide than cancer. Common infections, such as pneumonia, can develop into more severe conditions if no effective antibiotics are available.

4 National action plan on antimicrobial resistance in humans Denmark is not immune to this development. We must keep AMR on the political agenda by It is important to act in time and use every tool integrating AMR and its implications into other at our disposal. I am therefore pleased that future healthcare plans. the government (The Social Democratic Party, I look forward to following the implementation The Liberal Party and the Moderates) has of the action plan in collaboration with the reached an agreement with the Green Left, parties behind the agreement, and I hope that, the Denmark Democrats, The Liberal Alliance, in addition to the concrete initiatives, it will help the Conservative People’s Party, the Red-Green foster ongoing commitment both within the Alliance, the Social Liberal Party, the Alternative sector and internationally. and the Danish People’s Party on the National action plan on antimicrobial resistance in humans. It strengthens and broadens the efforts to combat antimicrobial resistance with 21 initiatives across four priority areas Sophie Løhde, and several cross-cutting efforts. The four Minister of the Interior priority areas are: and Health 1. Antimicrobial stewardship 2. Access to antimicrobials 3. Infection prevention and control 4. International engagement The action plan targets antimicrobial resist- ance in humans and focuses on the healthcare sector. However, combating AMR is based on interdependence between humans, animals, food and the environment. The government and the parties to the agreement recognise that the AMR challenge should be viewed from a One Health perspective, integrating health considerations across all sectors. The govern- ment has therefore launched an initiative to draft a new One Health strategy addressing antimicrobial resistance. The initiatives in the action plan are fully financed for the period 2025–2028. National action plan on antimicrobial resistance in humans 5 Background on antimicrobials and antimicrobial resistance (AMR) What are antimicrobials? • Antimicrobials kill or inhibit the growth of • The use of broad-spectrum antimicrobials microorganisms and are important because carries a higher risk of resistance development they enable us to treat infections. than the use of narrow-spectrum products, as they create a more intense selection pressure • Antimicrobials comprise several different types and thereby increase the likelihood that resistant of medicinal products. The most well-known microorganisms survive. type is antibiotics, which are used to treat bacterial infections. • It is generally recommended to use a narrow- spectrum antimicrobial rather than a • However, there are also drugs for the treatment broad-spectrum one, if both are equally effective. of fungi (antimycotics/antifungal agents), parasites (antiparasitics) and viruses (antivirals). • In certain cases, it may be necessary to use broad-spectrum antimicrobials, for example • Some are effective against only a few specific if a patient is seriously ill and treatment must microorganisms and are therefore referred to be initiated before a specific pathogen can be as narrow-spectrum antimicrobials. Others are identified. active against a wide range of microorganisms and are therefore classified as broad-spectrum antimicrobials. What is antimicrobial resistance (AMR)? • Microorganisms can, through random mutations, • Infections involving resistant microorganisms develop defence mechanisms that render are frequently more complex and challenging antimicrobials less effective or completely to treat than infections caused by susceptible ineffective. This is referred to as antimicrobial strains. It consequently increases the risk of resistance (AMR). serious disease and death. • A microorganism that has developed such • It may be necessary to use alternative antimicro- defence mechanisms is referred to as a resistant bials, which are associated with more severe microorganism. adverse effects than the standard treatment options. • The use of antimicrobials creates a selection pressure that favours microorganisms that have • Infections caused by resistant microorganisms already developed antimicrobial resistance. place significant demands on infection control measures aimed at preventing transmission • This means that these microorganisms are and thus impose a substantial burden on the more likely to survive and reproduce, thereby healthcare system. contributing to a higher overall prevalence of resistant microorganisms. • In some rare instances, certain microorganisms exhibit resistance to such a wide range of • All use of antimicrobials entails a risk of antimicrobials that no treatment options are developing resistance. It is therefore essential available. that antimicrobials are only used when clinically appropriate. • Antibiotic resistance represents the most pressing AMR challenge; however, resistance among fungi, parasites and viruses is an increasing concern.

6 National action plan on antimicrobial resistance in humans The stories of Peter, Malene and Thorvald Peter, 67 years old, underwent heart valve surgery in 2015 and later required reoperation due to bleeding following the initial procedure. He was discharged three days post-surgery but, a few days later, developed a systemic infection that necessitated readmission. He remained hospitalised for a week before the doctors, with the help of various antibiotics, managed to bring the infection under control. According to Peter, the operation most likely saved his life. However, given the inherent risk of infection associated with the procedure, it would have been extremely hazardous to perform without the option of administering antibiotics. Malene, 46 years old, is a kidney transplant recipient undergoing immuno- suppressive therapy, which makes her particularly vulnerable to infections. In 2024, she developed a urinary tract infection caused by resistant bacteria. As a result, the antibiotic treatment was more complex and required a longer duration than is typically the case. Consequently, her already declining renal function deteriorated further, resulting in loss of kidney function and the need for dialysis treatment. Although the treatment was ultimately effective, it had a substantial impact on Malene’s health and quality of life. Kidney transplant recipients are particularly vulnerable to resistant bacteria and rely on prompt and effective antibiotic treatment in the event of infection. Thorvald, 69 years old, has been living with chronic obstructive pulmonary disease (COPD) for over 15 years. As a result, he is at increased risk of pulmonary infections such as pneumonia and pleurisy. Prior to the COVID-19 pandemic, Thorvald would typically experience pneumonia between six and eight times a year. The intervals between infections have increased, but the infections themselves have become more severe. The most recent case of pneumonia took five weeks to bring under control. Like other patients with COPD, Thorvald is therefore heavily dependent on access to effective antibiotic therapy. Source: Peter’s story was obtained from the Danish Heart Foundation, Malene’s from the Danish Kidney Association and Thorvald’s from the Danish Lung Association. National action plan on antimicrobial resistance in humans 7 The threat of antimicrobial resistance Antimicrobials are important and often life-saving At the global level, antimicrobial resistance has been medicines used to treat infections caused by recognised as one of the greatest threats to public microorganisms such as bacteria, fungi or parasites. health, by, among others, the World Health Organiza- Stories like Peter’s and Thorvald’s highlight that tion (WHO). It is estimated that one in five bacterial antimicrobials form the cornerstone of our modern infections in the EU/EEA is currently caused by resistant healthcare system and, by extension, our collective bacteria, and that more than 35,000 people in Europe health. The most well-known type of antimicrobials is die each year as a result of infections with resistant antibiotics, which are used to treat bacterial infections. bacteria. On a global scale, AMR is estimated to have caused more than 1.27 million deaths in 2019. It is The use of antimicrobials is not without consequences. estimated that AMR could potentially cause up to Microorganisms exposed to antimicrobials may, over 10 million deaths by 2050 if action is not taken to time, develop defence mechanisms that enable them counter its development. to withstand these drugs. Antimicrobial resistance occurs when microorganisms become resistant to the Widespread resistance also has consequences for the medicinal products used to eliminate them. All use of wider economy. Resistance directly leads to increased antimicrobials entails a risk of developing resistance. costs in the healthcare system due to more expensive treatments, longer hospital stays and the need for Widespread resistance would mean that common specialised infection prevention and control meas- infections such as urinary tract, skin or respiratory ures. AMR also has indirect economic consequences infections would become difficult or eventually for society, including increased sick leave due to impossible to treat. They could lead to serious illness prolonged illness. and, in the worst-case scenario, death. Malene’s story clearly illustrates the profound human consequences Projections indicate that, in the coming years, up to of antimicrobial resistance. Resistance also compli- 10 percent of healthcare expenditure on infectious cates the use of modern treatments that suppress diseases in OECD and EU countries will be spent on the immune system, such as cancer therapy or managing complications arising from antimicrobial organ transplantation. AMR will also increase the resistance. According to the Center for Global risks associated with routine procedures, such as Development, the global direct healthcare costs of hip replacements, as post-operative infections AMR exceed DKK 470 billion annually, and this figure become more difficult to treat. could rise to more than DKK 1,151 billion per year by 2050. Based on OECD calculations, antimicrobial resistance is currently associated with annual direct healthcare costs of DKK 400 million in Denmark.

8 National action plan on antimicrobial resistance in humans Antimicrobial resistance from a One Health perspective Antimicrobial resistance is not only a challenge collaboration between Statens Serum Institut and for humans. Resistance is also present in micro- the National Food Institute at the Technical University organisms in animals, plants and the environment of Denmark. DANMAP issues an annual report detailing that can spread to humans. The occurrence of trends in antibiotic consumption and resistance resistance in microorganisms in humans is affected prevalence and highlighting key developments by the animals we come into contact with, the food in the Danish AMR landscape. The cross-sectoral we eat, and the environment we occupy. collaboration in DANMAP is recognised internationally as a success story for the One Health approach. Efforts to combat antimicrobial resistance in humans cannot stand alone. Collaboration is necessary In 2017, the former Ministry of Environment and across the human, veterinary, food and environmental Food and the Ministry of Health and the Elderly sectors through a One Health approach that developed a One Health strategy to combat integrates the health of people, animals and the antibiotic resistance. The strategy contains five environment. objectives, all aimed at reducing antibiotic use and preventing the development of resistance Extensive efforts are underway both within and across in humans and animals alike. sectors to combat AMR. Denmark has a long-standing tradition of strategic One Health collaboration on AMR, The One Health strategy has been successful in with specific action plans implemented within each setting the direction for Denmark’s efforts to combat sector. The present action plan should be viewed antibiotic resistance. The importance of a strong in conjunction with the National action plan on One Health approach will only continue to grow in antimicrobial resistance in animals and food the future. 2024–2027, published by the Danish Veterinary and Food Administration in 2024. This action plan outlines We are therefore taking the initiative four strategic priority areas in the veterinary and to develop an updated One Health strategy food sectors. Each focus area includes objectives supported by concrete measures and activities. to guide future efforts for combating antimicrobial resistance and promoting Since 1995, Denmark has had an integrated cross-sectoral surveillance of the use of antimicro- health for all. bials and the prevalence of resistant bacteria in animals, food and humans through the DANMAP THE ENVIRONMENT ONE HEALTH HUMAN ANIMAL HEALTH HEALTH National action plan on antimicrobial resistance in humans 9 Since 2016, we have reduced the number of The number of invasive cases of monitored prescriptions in the primary care sector (measured bacterial species, in which a person is infected as prescriptions per 1,000 inhabitants per year) with bacteria, has increased by 25 percent and have nearly reached the target set in 2017. from 2014 to 2024. 500 450 400 350 300 +25% 250 200 2016 2017 2018 2019 2020 2021 2022 2023 2024 A larger share of total antibiotic use in primary care (measured as the number of prescriptions per 1,000 inhabitants) now consists of the narrow- spectrum antibiotic penicillin V, but we have not yet reached the target. 45 Source: Statens Serum Institut 40 35 In particular, the incidence of multidrug- 30 resistant intestinal bacteria – carbapene- mase-producing Enterobacterales (CPE) – 25 has risen sharply, making them difficult, 20 and in some cases impossible, to treat. 2016 2017 2018 2019 2020 2021 2022 2023 2024 700 600 We have reduced the use of critically 500 important antibiotics (measured as DDDs per 100 bed-days) to a significantly lower level. 400 26 300 25 200 100 24 0 23 20 20 2008 09 20 20 20 20 20 10 11 12 13 14 15 20 20 20 20 20 16 17 18 19 20 20 20 20 20 21 22 23 24 22 Source: Statens Serum Institut 21 20 2016 2017 2018 2019 2020 2021 2022 2023 2024 Source: Statens Serum Institut And the frequency of antimicrobial shortages has increased significantly. 5.9 52.4 Average number of packs affected Average number of packs affected by supply shortages in 2011 by supply shortages in 2024 Source: The Association of Danish Pharmacies Note: The annual average number of antibiotic packs (J01) affected by supply shortages is recorded for both full-line wholesalers on the first tariff day of each 14-day pricing period.

10 National action plan on antimicrobial resistance in humans 80.1% In 2023, 80.1 percent of total antibiotic consumption in Denmark consisted of antibiotics in the WHO’s Access group, which carry the lowest risk of promoting resistance. Denmark is therefore the EU country that, measured as a share of total consumption, is best at making use of antibiotics associated with the lowest risk of resistance development. Note: Each icon represents one hundredth of Denmark’s antibiotic consumption, measured in DDDs per 1,000 inhabitants per day in 2023, broken down according to the WHO’s AWaRe classification into the Access group (green) and the remaining groups – Watch, Reserve, and Unclassified (grey). Source: ESAC-Net The resistance level for many microorganisms remains low in Denmark. However, in many other regions of the world, antimicrobial resistance already poses a major challenge. Percentage of isolates with resistance <5% 40 to <50% 5 to <10% 50 to <60% 10 to <20% 60 to <70% 20 to <30% 70 to <80% 30 to <40% ≥80% Note: The map shows the distribution of K. pneumoniae isolates resistant to critically important third-generation cephalosporins. Source: Global Research on Antimicrobial Resistance (GRAM) Due to high global resistance levels, in 2019 AMR If no action is taken, by 2050 that number was estimated to have caused is expected to rise to over 1.27 million deaths 10 million deaths Source: WHO National action plan on antimicrobial resistance in humans 11 Overview of priority areas, initiatives and objectives in the national action plan on antimicrobial resistance in humans Antimicrobial stewardship Access to antimicrobials We must reduce the use of antimicrobials We must work towards and prioritise the use of antimicrobials that a more stable and improved carry a lower risk of resistance development. supply of antimicrobials. 1. Strengthened collaboration between 6. Increased European cooperation hospitals and municipalities, general on innovative procurement models practitioners and practising specialists 7. Increased Nordic cooperation on antimicrobial resistance on the availability of narrow- 2. Pilot project to strengthen point-of-care spectrum antibiotics diagnostics 8. Exemption from annual fees for 3. Assessment of prescription requirements antimicrobials for topical antimicrobials 4. Increased harmonisation of medicinal product packaging 5. Increased focus on antimicrobial resistance in primary care Cross-cutting initiatives 18. Establishment of a national AMR advisory group 19. Monitoring 20. Research on antimicrobial resistance 21. Awareness and information campaigns Infection prevention International and control engagement We must combat any increase and We must strengthen our international work towards a reduction in the amount involvement and contribution to global of infections requiring treatment. efforts to combat antimicrobial resistance. 9. Enhanced training in hygiene and 14. Increased international engagement infection prevention and control and cooperation on AMR 10. Health Technology Assessment (HTA) 15. Appointment of a High-Level of pneumococcal vaccination Representative (HLR) 11. AMR as a parameter in vaccine 16. Developing and implementing assessment sustainable AMR solutions in low- and middle-income countries 12. Simplification of guidance materials through ICARS 13. Elimination of administrative barriers to 17. Support for global capacity building vaccines with conditional reimbursement New One Health Strategy on Antimicrobial Resistance

12 National action plan on antimicrobial resistance in humans Photo: Danish Health Authority National action plan on antimicrobial resistance in humans 13 Priority area 1: Antimicrobial stewardship Nina’s story Nina is a physician at the Department of Clinical Microbiology at Aalborg University Hospital. Nina is involved in both laboratory work and clinical consultations to help diagnose patients. Drawing on test results, she provides guidance to colleagues across hospitals in the region on the most suitable treatment for each patient. While it remains relatively uncommon, Nina is encountering noticeably more patients who are ill due to highly resistant microorganisms than she did in the past. This means that she has to carry out more tests, which requires both time and resources. This may impact patients, as delays in identifying the appropriate treatment may contribute to a deterioration in their condition. Resistant micro- organisms frequently require treatment with broad-spectrum antibiotics, which may be associated with increased side effects for patients. At the same time, according to Nina, being placed in isolation is a distressing experience for patients, but it is a necessary measure to prevent microorganisms from spreading to other patients. Source: Nina’s story was obtained from the Danish Society for Clinical Microbiology. We must protect our antimicrobials. Without action, A correct and timely diagnosis is essential to stories like Nina’s may become increasingly frequent. ensuring the rational use of antimicrobials. For Excessive and unnecessary use of antimicrobials example, broad-spectrum antibiotics are often accelerates the development of resistance, ultimately used as a temporary measure in serious situations diminishing their effectiveness against the micro- where the physician is unable to rule out a bacterial organisms they are designed to combat. It is therefore infection or accurately identify the pathogen. essential that we use antimicrobials only when Accurate diagnostics are equally important in less necessary and when they will benefit the patient. This serious infections. Accessible, accurate and rapid is also referred to as rational use of antimicrobials. diagnostics make it possible to target treatment and avoid overuse of antibiotics. We are therefore committing to reducing The field of diagnostics is constantly evolving, yet the use of antimicrobials and prioritising existing diagnostic tools are often characterised as antimicrobials associated with a lower risk inadequate and slow. We will therefore explore the of resistance development. potential of scaling up new diagnostic tools through a research-based pilot project. The pilot project will be This serves not only the interest of society as a whole, established through a public–private partnership with but also those of each individual. Treatment with the aim of assessing the potential of new diagnostic antimicrobials – particularly broad-spectrum ones – tools to support rapid point-of-care diagnostics can have a significant impact on the body’s normal in the primary care sector, with a view to reducing microbiota. The microbiota plays a vital role in keeping antibiotic consumption. the body healthy and in balance, and disruptions can make individuals more susceptible to illness.

14 National action plan on antimicrobial resistance in humans The ‘Fri for UVI’ pilot project: Preventing urinary tract infections in nursing homes Urinary tract infections (UTIs) pose a major challenge in many nursing homes, where many residents develop UTIs, and many others receive unnecessary antibiotic treatment for suspected infections. Excessive use of antibiotics can cause side effects for the individual and increase the risk of resistance development at the societal level. Part of the overuse is due to the widespread reliance on urine dipsticks to diagnose urinary tract infections. Urine dipsticks can detect bacteria in the urine, but a positive result does not necessarily indicate a urinary tract infection. This is particularly relevant for older individuals, who often have a naturally higher bacterial presence in the urine. Odense Municipality, Nyborg Municipality and the Department of Clinical Microbiology at Odense University Hospital therefore launched Fri for UVI, a pilot project aimed at preventing urinary tract infections and reducing the use of antibiotics for their treatment. The Depart- ment of Clinical Microbiology developed a short interactive training seminar in cross-sectoral collaboration with two selected nursing homes: Vindinge Landsbycenter and Blomsterdalen Nursing Home. The seminar aimed to promote a systematic focus on basic preventive measures and to clarify when the use of antibiotics is clinically appropriate. In addition, a decision support tool was developed for use by nursing home staff in their daily work to assess the risk of urinary tract infections. All staff and management at the two nursing homes, affiliated general practitioners and key municipal representatives participated in the seminar training. The two participating nursing homes subsequently halved their use of antibiotics for the treatment of urinary tract infections, and the incidence of UTIs was reduced. The marked decrease in antibiotic consumption was partly attributable to the discontinuation of urine dipstick testing. The results of the pilot project have been so positive that Nyborg Municipality has decided to scale up the concept to all nursing homes in the municipality. Odense Municipality also has a plan to fully implement the concept in all municipal nursing homes. Ensuring the rational use of antimicrobials is not healthcare services to be delivered outside of an easy task. Nevertheless, several topical anti- hospitals. This likewise applies to tasks related to microbials, such as creams for fungal infections, infection prevention and control, as well as the rational can be purchased over the counter without a use of antibiotics. However, much of the specialised prescription. However, they may pose a potential expertise is located in hospitals. The action plan will risk of resistance development if not used correctly. help ensure that this expertise is accessible closer An assessment will therefore be initiated to assess to citizens by strengthening collaboration between whether there is a need to extend prescription hospitals and municipalities, general practitioners requirements to additional topical antimicrobials and practising specialists, including through the and to examine the potential consequences of forthcoming health councils. This is intended to ensure introducing such a measure. that the right national frameworks are in place to support effective local cross-sectoral collaboration, In the future, the healthcare system in Denmark as seen, for example, in the Fri for UVI project. will also move closer to the citizens, allowing more National action plan on antimicrobial resistance in humans 15 General practitioners play a key role in addressing The national action plan will antimicrobial resistance. For most people, the general practitioner is their first point of contact with the strengthen antimicrobial stewardship healthcare system, and general practitioners are efforts by: responsible for prescribing approximately 75 percent 1. Strengthening cooperation between hospitals of all antibiotics in Denmark. However, general and municipalities, general practitioners and practitioners do not have the same access to a practising specialists to ensure access to specialised peer network with whom they can discuss guidance on infection prevention and control antimicrobial resistance. We will activate the existing and the rational use of antibiotics, thereby making cluster networks under the Quality in General Practice expert knowledge accessible closer to citizens. (KiAP) initiative to create a framework for professional knowledge-sharing and data-driven quality develop- 2. Strengthening diagnostics through a research- ment. based pilot project developed in a public–private partnership to generate knowledge on how rapid Antimicrobial stewardship is not solely about limiting point-of-care diagnostics can be implemented the use of antimicrobials. They are both useful and in primary care. necessary in many situations. But they must be used correctly. At the correct dosage and for the 3. Assessing the need for prescription requirements appropriate duration of treatment. We will therefore for topical antimicrobials currently available over intensify ongoing efforts to adjust medicinal product the counter to promote rational use. packaging to align with modern and more restrictive 4. Adjusting the packaging of antimicrobials treatment recommendations. to ensure greater alignment with treatment guidelines and updated package leaflets. 5. Improving quality in general practice through a cluster package on the rational use of antimicrobials for use within quality clusters in general practice, ensuring that knowledge and experience on rational use are accessible to general practitioners. Rational use of antimicrobials According to the Danish Health Authority’s guidance on antibiotic prescribing, rational use of antibiotics includes, among other things, the following: • Antibiotics should only be used when they can prevent serious or life-threatening illness or significantly shorten the course of illness. • Antibiotics should only be used when clinical and diagnostic findings provide at least a reasonable likelihood that the infection is caused by bacteria. • The selected antibiotic should be as narrow-spectrum as possible, and the treatment duration should be kept to a minimum. • If treatment with the selected antibiotic proves ineffective, the choice of antibiotic should be reassessed. The fundamental principles of rational antibiotic use can also be applied to the rational use of other antimicrobials.

16 National action plan on antimicrobial resistance in humans Photo: Danish Health Authority National action plan on antimicrobial resistance in humans 17 Priority area 2: Access to antimicrobials Kristina’s story Kristina is a specialist in infectious diseases and works as a chief physician at Gødstrup Regional Hospital. Kristina contributes, among other things, to the develop- ment of treatment guidelines designed to help her colleagues choose the right antibiotic. The guidelines are instrumental in ensuring the rational use of antibiotics. However, Kristina finds that antimicrobial shortages make it difficult to update the guidelines. She has been involved in updating multiple treatment guidelines intended to promote a shift from broad-spectrum antibiotics to more narrow-spectrum options. The challenge, however, is that there is an insufficient supply of the alterna- tive antibiotics, creating a risk of exhausting existing medical stockpiles. As a result, the new treatment guidelines have to be put on hold. This may accelerate the development of resistance to some of the antibiotics we are trying to preserve, and, in the worst-case scenario, we risk losing their effectiveness in the future. Source: Kristina’s story was obtained from the Danish Medical Association. Rational use of antimicrobials requires access to Kristina’s experiences clearly demonstrate how the appropriate medicines. Limited availability and the availabilityof appropriate antimicrobials affect antimicrobial shortages may lead clinicians to resort both patients and society. to less suitable alternatives, which potentially carry a greater risk of resistance development. This may We will therefore work to ensure mean that infections have to be treated with a more stable and improved supply broad-spectrum antibiotics, thereby promoting resistance development. of antimicrobials. Piperacillin/Tazobactam shortage In 2016, an explosion occurred at a pharmaceutical factory in Jinan, China. The factory produced the majority of the active substances in the combination antibiotic piperacillin/tazobactam, which is widely used in Denmark to treat severe infections. The explosion impacted global production to such an extent that Denmark temporarily faced major difficulties in the supply of the medicine. As a result, seriously ill patients in Denmark had to be treated with a broader-spectrum antibiotic, which may have contributed to the further development of antimicrobial resistance. The incident highlights that antimicrobial shortages can significantly threaten efforts to combat antimicrobial resistance, and that ensuring access to antimicrobials is a global challenge requiring cross-border solutions.

18 National action plan on antimicrobial resistance in humans The global supply of medicines is complex and As part of the National Action Plan, we are working to involves many stages. Denmark cannot address these participate in an innovative joint Nordic procurement challenges alone. It is therefore important that we scheme founded on a subscription-based model. look to partners and enter into mutually beneficial This initiative is intended to support continued access agreements. In this context, the European Union’s to critical narrow-spectrum antibiotics in Denmark strategic autonomy plays a key role. The National and across the Nordic region. Action Plan will include cross-border initiatives to It is important to look beyond national borders. strengthen access to antimicrobials, both at EU level However, there are also initiatives that can be and within the Nordic cooperation framework. implemented at national level. Every year, several The market for antimicrobials is challenging. On the antimicrobials are removed from the Danish market, one hand, we want to ensure access to antimicrobials as they are no longer considered commercially viable and support the development of new ones. However, in Denmark. This reduces our arsenal in the fight at the same time, we must reduce our use of anti- against infections and resistance. We are taking steps microbials. This highlights the need for innovative and to eliminate the financial barrier posed by the annual forward-thinking solutions. Sweden and the United marketing authorisation fee for systemically adminis- Kingdom have successfully implemented pilot tered antibiotics, in order to help retain more anti- initiatives involving alternative reimbursement models, microbials on the market. which have supported continued access to anti- microbials. Enhanced collaboration between countries can contribute to jointly supporting the necessary The national action plan will development and access to antimicrobials. We will reinforce efforts to secure access work to further innovative, EU-wide solutions that can, to antimicrobials by: for instance, create initiatives for pharmaceutical companies to supply the market or develop new 6. Exploring the potential for participating in antimicrobials. an innovative joint European procurement model to safeguard access to essential antibiotics. There is already a well-established Nordic cooperation in the field of antimicrobial resistance. This coopera- 7. Strengthening Nordic cooperation on the develop- tion must be preserved and strengthened. Unlike ment of a joint procurement model to improve much of the world, the Nordic countries continue to the availability of narrow-spectrum antibiotics use narrow-spectrum antibiotics, which are associ- that are particularly used in Denmark and the rest ated with a lower risk of resistance development. of the Nordic region. This also means that, from a global perspective, the 8. Exempting antimicrobials from annual fees to total market for these medicines remains limited. remove unnecessary barriers to marketing and keep antimicrobials on the market in Denmark. Subscription model for antimicrobials In a subscription model, one or more countries enter into a contract with one or more manufacturers producing antimicrobials. The contract entails that the participating countries receive a supply guarantee in return for a fixed payment to the manufacturers. The aim of the model is to fully or partially decouple manufacturers’ earnings from national consumption of antimicrobials. The model is designed to ensure stable access to antimicrobials while avoiding incentives that may lead to overconsumption. There are several variants of the subscription model, which may differ in aspects such as payment size, the degree of decoupling, and the specific obligations of the manufacturers. Both Sweden and the United Kingdom have implemented subscription models based on initial pilot projects. National action plan on antimicrobial resistance in humans 19 Priority area 3: Infection prevention and control The stories of Pia and Lykke Pia works as a service assistant in the Emergency Department at Randers Hospital. There is a high turnover of patients in the department, which creates a significant risk of infection transmission. This means that Pia must place strong emphasis on infection prevention and control in her daily tasks. This can range from putting up signs in patient rooms to inform colleagues about the required personal protective equipment, to thoroughly cleaning the rooms in accordance with professional guidelines. Lykke works as a social and healthcare assistant in home care in the Egevang district of Nyborg Municipality. Infection prevention and control also plays a significant role in her daily work. Lykke’s service users live in their own homes, so she must exercise particular caution to avoid transmitting infections between households. It can be challenging, but she finds that simple practices such as hand disinfection and wearing gloves can help prevent infections in all situations. Both Pia and Lykke report that their infection prevention and control efforts provide great value for service users by keeping them healthy, preventing hospital admissions and reducing the need for medication. Source: Pia and Lykke’s stories were obtained from FOA. Resistant microorganisms, like other microorganisms, also be freely accessible for use in workplaces by can spread as infections between people, which other staff groups working in close contact with increases the prevalence of resistance. A high level service users. The objective is to enhance the of infections also leads to increased use of antimicro- knowledge base of new employees to enable their bials, which in turn contributes to a higher prevalence active participation in infection prevention and control of antimicrobial resistance. One of our most effective efforts, while also upskilling both skilled and unskilled weapons against antimicrobial resistance is therefore staff already in the workforce. to prevent infections – such as urinary tract and Extensive and complex guidance materials can respiratory infections – in the first place. make it difficult for staff to prioritise their efforts. We are therefore taking concrete steps to simplify We commit to combating any upward and prioritise the existing guidance material in trend and working towards a reduction in order to provide practical and usable guidance. the level of infections requiring treatment. The initiative will have a broad scope and will be based on the needs of the staff. The aim is to benefit A large part of the fight against the development of service users through improved infection prevention resistance takes place through daily hygiene and and control efforts, while also easing the burden on infection prevention and control efforts, such as those staff by removing unnecessary administrative tasks. carried out by Pia and Lykke. The measures may seem Vaccines also play a key role in the effort to prevent simple. Handwashing. Thorough cleaning. Disinfection. infections and resistance. Vaccines prevent infections However, preventing infections in practice requires and reduce the need for treatment with antimicrobi- knowledge and skills. As part of the National Action als. Vaccination against infections caused by bacteria Plan, training in hygiene and infection prevention and – such as pneumococci – that are typically treated control will be reinforced by the development of new with antibiotics directly reduces antibiotic consump- educational materials covering hygiene, cleaning and tion. Other vaccines also reduce usage by preventing infection prevention and control. The material will be infections that may lead to secondary bacterial incorporated into the social and healthcare assistant infections or situations where antibiotics are used and service assistant training programmes and will as a precaution. This is intended to complement

20 National action plan on antimicrobial resistance in humans Denmark’s already well-functioning seasonal An effort to improve the use of vaccines to prevent vaccination programme, which helps protect the most the development of resistance does not only involve vulnerable members of society against COVID-19 and focusing on new vaccines. We must also consider how influenza. In 2024, the programme achieved coverage to make the best use of the vaccines that are already rates of 74.9 percent for COVID-19 vaccination and being offered. Many physicians are already aware 75.7 percent for influenza vaccination among citizens of how vaccines can be used to prevent disease and aged 65 and over – the highest uptake in the Nordic the development of resistance. Unfortunately, they region by a significant margin. encounter administrative barriers when advising their patients about vaccines. Today, it is difficult for It is important that all decisions to include vaccines general practitioners to gain an overview of which in a public programme have a solid basis in the of their patients might benefit from a vaccine offered best available scientific evidence. The Danish Health with conditional reimbursement. We are therefore Authority therefore conducts scientific assessments removing administrative and legal barriers, so that of vaccines prior to any decision on their inclusion general practitioners can access information on in a public programme. A Health Technology Assess- relevant patients’ vaccination status and, on that ment (HTA) of pneumococcal vaccination is therefore basis, offer vaccination. For patients, the initiative will being initiated. During the COVID-19 pandemic, contribute to a smoother vaccination process with pneumococcal vaccination was offered as a measure fewer visits to the doctor. Overall, this can help ensure to protect particularly vulnerable groups and ease that vaccines benefit more vulnerable individuals. the burden on the healthcare system. The assessment will, among other things, examine the benefits and advantages of offering the vaccine as part of a public The national action plan will programme. reinforce infection prevention When the Danish Health Authority assesses vaccines, and control efforts by: several considerations are already taken into account, such as preventive potential and the severity of the 9. Strengthening training in hygiene and disease. But there is potential in adopting a broader infection prevention and control by developing perspective. With the National Action Plan, we will new educational materials on hygiene and therefore introduce the effect of vaccines on infection prevention for use in social and health- antimicrobial resistance as a parameter in future care assistant and service assistant training assessments conducted by the Danish Health programmes, as well as in workplaces for other Authority. This is intended to provide a broader staff groups. perspective on vaccines and ensure a consistent 10. Conducting a Health Technology Assessment focus on AMR, highlighting their value in preventing (HTA) of pneumococcal vaccination to provide resistance. a well-founded basis for decisions on a potential public vaccination programme. 11. Introducing antimicrobial resistance as a parameter in the Danish Health Authority’s future professional assessments of vaccine effectiveness to ensure sustained focus on the potential of vaccines to prevent AMR. Vaccines with 12. Simplifying guidance materials to streamline conditional and support staff in their infection prevention reimbursement and control efforts, and to eliminate unnecessary administrative burdens. Some vaccines are offered with conditional 13. Improving general practitioners’ access to reimbursement for clearly defined population the Danish Vaccination Register (DDV) to enhance groups who meet specific medical eligibility citizens’ access to vaccines with conditional criteria. It is the physician who determines reimbursement. whether an individual belongs to one of the groups eligible for conditional reimbursement. National action plan on antimicrobial resistance in humans 21 Priority area 4: International engagement Dr Chanda’s story Dr Duncan Chanda is Director of Infectious Diseases at the University Teaching Hospital in Lusaka, the capital of Zambia, and has served as project lead on one of ICARS’ 55 projects across 24 low- and middle-income countries. The purpose of the project was to reduce unnecessary use of antibiotics in patients with bloodstream and urinary tract infections. According to Dr Chanda, it was not uncommon prior to the project for a patient to receive three types of antibiotics, even though just one would have been sufficient. In close collaboration with local staff such as Dr Chanda, ICARS contributed knowledge and practical tools to support decision-making on when antibiotics should be used. The project led to a significant reduction in antibiotic use, which, according to Dr Chanda, has benefited both individual patients and the wider community by reducing the development of resistance. Source: Dr Chanda’s story was obtained from ICARS. Microorganisms do not respect national borders. through the joint human-animal surveillance They travel across countries with the help of people, programme under the DANMAP collaboration. animals, plants and food. At the same time, an We therefore have valuable experience and increasing number of countries are facing growing knowledge that can also benefit other countries. challenges related to antimicrobial resistance. Denmark’s expertise should be directed towards areas where the need is most acute and the consequences Although Denmark has a low level of resistance most severe. Accordingly, Denmark’s international compared to other countries, international trade and engagement will primarily target low- and middle- travel patterns present a risk of resistant bacteria income countries. Efforts will also focus on initiatives entering the country. It is therefore also in Denmark’s within the European context, where geographical interest to assist other countries in combating proximity and cross-border movement increase antimicrobial resistance. Dr Chanda’s story illustrates the risk of infection spread. Denmark’s EU Presidency how development programmes targeting antimicro- in the second half of 2025 will also serve as a lever bial resistance can make a tangible difference in to highlight the issue of antimicrobial resistance at local communities. the European level. We will therefore commit to strengthening Building on the National Action Plan, Denmark will reinforce its international engagement and coopera- Denmark’s international engagement tion on antimicrobial resistance. The work will take and contribution to global efforts against place across a wide range of multilateral forums, antimicrobial resistance. such as the EU’s Health Emergency Preparedness and Response Authority (HERA), the EU collaboration We must do this both by supporting existing multi- JAMRAI-2, the UN, the WHO, and through bilateral lateral efforts relevant to AMR – such as the World cooperation under the Ministry of the Interior and Health Organization’s End TB Strategy, which aims to Health of Denmark’s Strategic Sector Cooperation eradicate tuberculosis globally – and through bilateral (SSC) with health authorities in a number of countries. cooperation, such as Denmark’s strategic sector collaboration with Ukraine, which, among other goals, Denmark’s engagement is supported by the appoint- aims to strengthen Ukrainian authorities’ efforts to ment of a High-Level Representative tasked with combat antimicrobial resistance. representing Denmark in international AMR forums with a One Health approach, contributing Danish Denmark has held a leading position in the field of solutions, and helping to shape the international antimicrobial resistance for many years, for example debate. This is intended to ensure that Denmark

22 National action plan on antimicrobial resistance in humans continues to play a leading role in shaping The national action plan will the AMR agenda and is regarded as a reliable international partner. reinforce efforts to promote international engagement by: As many collaborators as possible must be brought on board in the fight against antimicrobial resistance. 14. Actively applying Danish knowledge and In 2018, Denmark took the initiative to establish the experience to support initiatives to combat AMR International Centre for Antimicrobial Resistance in both bilateral and multilateral partnerships. Solutions (ICARS), with the aim of developing and 15. Appointing a High-Level Representative implementing collaborative programmes on AMR to promote Danish solutions, participate in with low- and middle-income countries. In 2021, international forums and influence the global ICARS transitioned to an independent, self-governing AMR agenda. organisation. Denmark must continue to support the important work carried out by ICARS to ensure locally 16. Providing financial support to the International sustainable One Health solutions. In addition to the Centre for Antimicrobial Resistance (ICARS) to National Action Plan, the government has allocated sustain its ongoing work with low- and middle- DKK 280 million to ICARS via Denmark’s development income countries in developing evidence-based aid over a four-year period from 2027–2030, to and sustainable AMR solutions adapted to local support its future work and development. contexts. Denmark will also increase its support for the WHO’s 17. Supporting the scaling up of the DTU National Food global One Health AMR efforts through the DTU Institute’s engagement as a WHO Collaborating National Food Institute in its role as a WHO Collabo- Centre to strengthen Danish research-based rating Centre. The increased support is intended advisory capacity and global capacity building. to assist the WHO in carrying out capacity-building activities in the AMR field, developing guidelines and tools to support the implementation of advanced genome sequencing methods, enhancing the capacity of national and international laboratories worldwide, and strengthening knowledge of and implementation of AMR surveillance. National action plan on antimicrobial resistance in humans 23 Cross-cutting initiatives In addition to the four areas of action, the action plan However, generating new knowledge is not the only includes a number of cross-cutting initiatives. They priority. We must also disseminate the substantial all aim to support the overall objective of the action knowledge we already possess. The action plan will plan: combating antimicrobial resistance. therefore also include awareness and information campaigns on AMR targeting both the general public AMR is not only a health issue but a societal issue. and healthcare professionals. An initiative will therefore be launched to establish a cross-sectoral advisory group involving a wide range of stakeholders to ensure focus on implemen- The national action plan will tation. It is important to include the perspectives of patients. Patient organisations should therefore reinforce cross-cutting efforts by: be included in the advisory group as representatives 18. Establishing a national AMR advisory group where of the patient perspective. The advisory group will stakeholders involved in the implementation of the be established in collaboration with the Danish action plan can meet and exchange experiences AMR Alliance, which has already brought together to support broad societal anchoring. a broad range of stakeholders in the field. 19. Continuously monitoring the objectives of the An important part of the follow-up is to monitor action plan to provide the necessary knowledge developments based on sound professional know- base for future decision-making in the AMR area. ledge. Accordingly, the objectives set out in the 20. Promoting further research in AMR to generate action plan will be subject to ongoing monitoring. new knowledge that can form an important Monitoring will be anchored in the DANMAP surveil- foundation for future efforts to combat anti- lance programme, which publishes an annual status microbial resistance. report tracking the use of antimicrobials and the occurrence of antimicrobial resistance. The report 21. Designing awareness and information campaigns includes a number of recurring elements published on AMR targeting both the public and healthcare each year, as well as a set of special analyses that professionals. vary from year to year. It is essential that research on AMR continues to advance. We will therefore seek to stimulate advanced research in AMR that may lay the foundations for future AMR efforts and, ideally, contribute to the development of new antimicrobials. The EU’s research and innovation framework programme, Horizon Europe, will play a central role in these efforts. DKK 231.5 million has been allocated from the 2025 research reserve to strengthen patient-centred, clinical and independent research, which may include research in AMR, as set out in “Agreement on the research reserve, etc. (Nov. 2024)”.

24 National action plan on antimicrobial resistance in humans Financial overview of the national action plan on antimicrobial resistance in humans The 2025 Finance Act allocates DKK 130 million to strengthen efforts against antimicrobial resistance in humans over a four-year period from 2025 to 2028. Funding is distributed as DKK 10 million in 2025, followed by DKK 40 million annually over the next three years. In addition, the government is allocating DKK 280 million to ICARS through development aid over a four-year period from 2027 to 2030. DKK million 2025-pl 2025 2026 2027 2028 Priority area 1 – Antimicrobial stewardship 1. Strengthened collaboration between hospitals and municipalities, gen- eral practitioners and practising specialists on antimicrobial resistance 0.4 5.2 10.0 10.0 2. Pilot project to strengthen point-of-care diagnostics - 2.4 2.4 3.8 3. Assessment of prescription requirements for topical antimicrobials 1.1 - - - 4. Enhanced harmonisation of pharmaceutical packaging 1.1 1.1 1.1 1.1 5. Increased focus on antimicrobial resistance in primary care 0.9 3.0 1.2 - Priority area 2 – Access to antimicrobials 6. Increased European cooperation on innovative procurement models - - - - 7. Increased Nordic cooperation on the availability of narrow-spectrum antibiotics 2.8 13.7 13.7 13.7 8. Exemption from annual fees for antimicrobials - 8.8 8.8 8.8 Priority area 3 – Infection prevention and control 9. Enhanced training in hygiene and infection prevention and control - 0.9 1.1 1.1 10. Health Technology Assessment of pneumococcal vaccination 0.9 1.1 - - 11. AMR as a parameter in vaccine assessment - - - - 12. Simplification of guidance materials 0.4 1.1 0.2 . 13. Elimination of administrative barriers for vaccines with conditional reimbursement - - - - Priority area 4 – International engagement 14. Increased international engagement and cooperation on AMR - - - - 15. Appointment of High-Level Representative (HLR) 0.5 1.0 1.0 1.0 16. Dissemination of sustainable AMR solutions in low- and middle-income countries through ICARS - - - - 17. Support for global capacity building 0.5 0.5 0.5 0.5 Cross-sectoral initiatives 18. Establishment of a national AMR advisory group - - - - 19. Monitoring 0.1 0.1 0.1 0.1 20. Research on antimicrobial resistance - - - - 21. Awareness and information campaigns 1.3 1.1 - - Total 10.0 40.0 40.0 40.0 Note: Any differences in total figures are attributable to rounding in the table. Source: Projections and calculations by the Ministry of the Interior and Health of Denmark. National action plan on antimicrobial resistance in humans 25 Appendix: Overview of objectives and indicators in the national action plan on antimicrobial resistance in humans National objectives on antimicrobial resistance We must reduce the We must work We must combat We must strengthen use of antimicrobials towards a more stable any increase and Denmark’s interna- and prioritise the and improved supply work towards a tional involvement use of antimicrobials of antimicrobials. reduction in the level and contribution that carry a lower of infections requiring to global efforts to risk of resistance treatment combat antimicrobial development resistance Indicators Number of Number of market Bacteraemias per Denmark supports dispensed antibiotic withdrawals of 100,000 inhabitants and collaborates prescriptions antimicrobials with the authorities in primary care of other countries and international organisations in the fight against AMR Use of Penicillin V Number of new Incidence of and Mecillinam as market registrations bloodstream a share of total anti- of antimicrobials infections with biotic use in primary carbapenem- care, measured resistant Klebsiella in prescriptions per pneumoniae 1,000 inhabitants (per 100,000 inhabitants) Use of critically Incidence of important antibiotics bloodstream measured in DDDs infections with per 100 hospital methicillin-resistant admissions Staphylococcus aureus (MRSA) (per 100,000 inhabitants) Share of total anti- Incidence of blood- biotic consumption stream infections represented by with third-generation the Access group cephalosporin- resistant Escherichia coli (per 100,000 inhabitants) Total antibiotic consumption in both primary care and the hospital sector, including care facilities (DDD per 1,000 inhabitants per day) Indicators Stable or positive trend Limited negative trend Marked negative trend

26 National action plan on antimicrobial resistance in humans