The threat of antimicrobial resistance

Antimicrobial resistance
© iStock/nopparit

Co-chair, John Ryan, addresses how the EU can become the best practice region in combating antimicrobial resistance.

Antimicrobial resistance (AMR or AR) is the ability of a microbe to resist the effects of medication that once could successfully treat the microbe. Resistant microbes are more difficult to treat, requiring alternative medications or higher doses of antimicrobials.

The ‘Transatlantic Taskforce on Antimicrobial Resistance’ (TATFAR) was created in 2009 to address the urgent threat of antibiotic resistance. TATFAR’s technical experts from Canada, the European Union (EU), Norway, and the United States (U.S.) collaborate and share best practices to strengthen domestic and global efforts in the following three key areas:

  • Improve appropriate therapeutic use of antimicrobial drugs in medical and veterinary communities,
  • Prevent healthcare- and community-associated drug-resistant infections,
  • Develop strategies for improving the pipeline of new antimicrobial drugs.

Directorate General for Health and Food Safety for the European Commission, John Ryan, is also co-chair of TATFAR. Ryan to SciTech Europa Quarterly about how antibiotics are posing as threat to antimicrobials.

Can you start by introducing us to TATFAR, and the role this Taskforce plays in antimicrobial resistance?

First, let me highlight the threat of antimicrobial resistance itself. Since their discovery, antimicrobials have transformed medicine and saved lives. However, these achievements are under threat due to the excessive and inappropriate use of antibiotics in human and animal health. This has led to a huge increase in multi-resistant bacteria, which are easily spread and difficult to treat. This is known as antimicrobial resistance (AMR). If antibiotics stop working, common infections would likely cause significant harm or death and routine medical procedures would be high risk. AMR causes an estimated 33,000 deaths in Europe and 700,000 deaths globally each year. It also results in €1.5bn (~£1.3bn) per year in healthcare costs and productivity losses in the EU.1 The EU is at the forefront in galvanising global political against AMR and promoting a One Health approach through our European One health action plan on AMR.2 As bacteria and viruses do not stop at borders, AMR is also recognised as a global threat to health security and human development.

The Transatlantic Taskforce on Antimicrobial Resistance (AMR), also known as TATFAR, was established by an agreement made at the 2009 EU-U.S. Summit. The aim was to create a transatlantic task force focused on appropriate use of antimicrobial drugs in the medical and veterinary communities, on prevention of both healthcare- and community-associated drug-resistant infections, and on strategies for improving the pipeline of new antimicrobial drugs such as antibiotics.

Starting with a cooperation between the USA and the EU, TATFAR has meanwhile expanded to include Canada and Norway. It is composed of the main government agencies working on AMR from the four TATFAR partners. Work is divided up into 20 action areas, each of which has a working group composed of people from the relevant agencies. Joint working takes place mostly via email and teleconferences. There are face-to-face meetings every two to three years. The TATFAR Secretariat, which organises meetings and coordinates the work, is based at the Centers for Disease Control and Prevention (CDC) in Atlanta, USA and it also hosts the TATFAR website with plenty of additional information on what TATFAR is doing.3 I am privileged to co-chair TATFAR, together with my counterpart Larry Kerr from the Department of Health and Human Services in the USA.

So how does TATFAR go about its work? Put simply, it is about exchange of information and cooperation between agencies with a common interest. TATFAR’s technical experts collaborate and share best practices to strengthen domestic and global efforts to reduce antimicrobial resistance. TATFAR has no budget or resources of its own. Its work is integrated into the work of the participating countries/organisations. This means that the work is planned a long time in advance to take account of the planning cycles of the partners.

TATFAR have three key areas of focus – how do you go about meeting these?

Below are a few examples of TATFAR activities from each of the main areas of action:

Improving the use of antimicrobial drugs

Here we are working on both the human and animal fields. Key activities in the human side are:

  • Co-operation on developing common structure and process indicators for antimicrobial stewardship programs,
  • Reviewing goals for appropriate human antimicrobial use in TATFAR countries,
  • Aligning campaigns that promote appropriate antimicrobial use, including collaboration with other partners, like the World Health Organization, to support World Antibiotic Awareness Week,
  • Compiling resources for how to assess appropriate outpatient antimicrobial use in TATFAR countries.

In the animal health field actions include:

  • Cooperation on ways to measure and report antimicrobial consumption by animal species in veterinary medicine,
  • Implementing Guidelines for Risk Analysis of Foodborne Antimicrobial Resistance in TATFAR countries,
  • Promoting the implementation of rapid and informative diagnostic tools to identify the most appropriate treatments for animals and trace the spread of AMR in the farm to fork continuum,
  • Aiming to better understand foodborne transmission of resistant infections, including publishing resources that can be used to improve surveillance methods.

Of course, we also exchange information on the key policies being implemented in this area in the TATFAR partners. We recognise that each partner has its unique set of responsibilities, competencies and ways of working. In the EU, we have been pleased to share our regulatory approaches to promote prudent and responsible use of antimicrobials in animals such as the recent Regulation (EU) 2019/6 on veterinary medicinal products and Regulation (EU) 2019/4 on medicated feed. We have also shared our guidelines for prudent use of antimicrobials in veterinary medicine and the EU guidelines for prudent use of antimicrobials in human health. We have been pleased to benefit from information on initiatives from the USA, Canada and Norway – for example on the Canadian regulatory framework for veterinary drugs, and the goals that the USA and Norway are working on to reduce inappropriate human use of antibiotics.

Prevention of drug resistant infections

TATFAR work includes:

  • Evaluating the burden of healthcare-associated infections (HAIs) in TATFAR countries through point-prevalence surveys and publishing studies on HAIs and antibiotic use across healthcare facilities,
  • Developing a common global system for sharing and analysing information about resistant bacteria,
  • Providing expertise in the development of a rapid alert system, led by World Health Organization, to notify countries of new and emerging types of resistance,
  • Working with partners, including the Clinical and Laboratory Standards Institute and the European Committee on Antimicrobial Susceptibility Testing, to harmonise antibiotic breakpoints.
  • Research and strategies for improving the pipeline of new antimicrobial drugs

Research is crucial to combatting AMR. For over 25 years, there has not been a completely new class of antibiotics to come onto the market. This is partly due to scientific challenges, and partly due to the rising cost of antimicrobial development and testing and relatively low profitability for manufacturers. This has discouraged innovation. TATFAR has sought to address these issues through actions such as:

  • Reviewing and suggesting economic incentives to encourage antibacterial drug discovery. TATFAR has published two papers about this work. One of these was a literature review on economic incentives for antibacterial drug development.4 The second paper was specifically on pull incentives,5
  • Exchanging information and cooperating on the development of research opportunities and partnerships such as the Innovative Medicine Initiative (IMI) with its New Drugs for bad Bugs programme, the Joint Programming Initiative on AMR (JPIAMR), and CARB-X to address challenges in combating antibiotic resistance,
  • Collaborating with partners to provide funding mechanisms to advance development of therapeutics, diagnostics, and vaccines,
  • Aligning clinical trial networks to evaluate novel antimicrobial products among critically important patient populations,
  • Working with TATFAR partners regulatory agencies to streamline the process of approving newly developed antibiotics and alternatives to antibiotics.

TATFAR recently published the report ‘Data for Action: Using available data sources at the country level to track antibiotic use’. Can you expand on this?

TATFAR collected information about the setting of targets for reducing antibiotic use in humans from Canada, Norway the USA as well as EU countries and Iceland.  Nine countries had established targets to reduce antibiotic use in humans, and 17 countries indicated that work to establish such targets was underway. In general, it was too early to say how far countries had got in achieving these targets.

What was useful was to be able to compare the different ways that the targets had been set and how they were measured as well as some of the different strategies and methods used for achieving them. For example, some countries had introduced incentives to support the achievement of targets.

Recently the Council of the European Union adopted Conclusions on the next steps towards making the EU a best practice region in combatting antimicrobial resistance.6 They include a call on Member States to establish national measurable targets, inter alia, on reduction of overall use of antimicrobials and monitor progress towards reducing the spread of AMR, taking into account to the appropriate extent the indicators developed by EFSA, EMA and ECDC. I am sure that the review carried out by TATFAR on targets for reducing antibiotic use in humans will be useful in taking forward this recommendation.

What is the importance of AMR research, and what are some of the challenges/limitations this brings? How are these overcome?

As mentioned already, research plays a pivotal role in addressing the threat from antimicrobial resistance. Research and innovation are firmly embedded in the EU action against AMR, being an integral plan of the EU one health action plan. The main priority is of course to develop new antimicrobials that can effectively treat currently resistant infections. As said above, that is not easy and requires continued and long-term investment in pharmaceutical research.

However, this is not the only direction where we are investing. Equally important is to develop new ways to prevent resistant infections: through innovation in the detection, surveillance and infection prevention and control of infectious diseases. This also requires new and more rapid diagnostic tools to allow doctors to quickly determine, for example, whether a patient has a bacterial or viral infection and hence, whether to prescribe antibiotics or not. In the EU, we have also developed EU Guidelines on the prudent use of antimicrobials in human health, addressed to not only doctors, but all healthcare professionals such as nurses, pharmacists and other healthcare workers on the appropriate ways of prescribing antibiotics only when they are really needed.7

To come back to research, vaccine development and vaccination (to protect against infectious diseases altogether), also plays a role in preventing the spread of AMR. The less people get sick from preventable diseases because they have been vaccinated, such as for example tuberculosis or pneumonia, the less they will need treatment with antibiotics.

Last but not least, we also need more research into AMR and the environment. This was also clearly recognised in the latest Commission’s policy paper from March this year on strategic approach to pharmaceuticals in the environment.8

What’s next for TAFAR?

TATFAR has been going for 10 years now. It has shown its usefulness and is included as an area for further development in the European Commission’s one health action plan against antimicrobial resistance.9 We have already begun work with our partners in the USA, Canada and Norway to plan our work for the next five years. We hope to agree an action plan for the period 2021-2025 in the autumn of 2020. We intend to continue our exchange and cooperation between agencies working on AMR in the human health, animal health and research fields. In addition, we will add some new area of cooperation. Here we will certainly be considering expanding our work on antibiotics in the environment, the use of whole genome sequencing and advanced digital techniques in combatting AMR. It is going to be an interesting, and very productive, next five years for TATFAR.

 

References

  • ECDC, OECD (2019). Antimicrobial resistance: Tackling the burden in the European Union. Online at: https://www.oecd.org/health/health-systems/AMR-Tackling-the-Burden-in-the-EU-OECD-ECDC-Briefing-Note-2019.pdf
  • https://ec.europa.eu/health/amr/action_eu_en
  • https://www.cdc.gov/drugresistance/tatfar/
  • Sciarretta K et al. (2016). Economic Incentives for Antibacterial Drug Development: Literature Review and Considerations From the Transatlantic Task Force on Antimicrobial Resistance. Clinical Infectious Diseases 2016;63(11):1470-4
  • C Årdal et al. (2017). Pull Incentives for Antibacterial Drug Development. Clinical Infectious Diseases 2017;65(8):1378-82. Online at: https://academic.oup.com/cid/article/65/8/1378/3862465
  • Council conclusions (2019). The next steps under a One Health approach towards making the EU a best practice region in combatting antimicrobial resistance (2019/C 214/01). Online at: https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=OJ:C:2019:214:FUL
  • https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=uriserv:OJ.C_.2017.212.01.0001.01.ENG&toc=OJ:C:2017:212:TOC
  • COM (2019). Communication from the European Commission to the Council and the European Parliament. European Union Strategic approach to pharmaceuticals in the environment COM (2019) 128 final. Online at: https://ec.europa.eu/environment/water/water-dangersub/pdf/strategic_approach_pharmaceuticals_env.PDF
  • Communication from the European Commission to the Council and the European Parliament (2017). A European One Health Action Plan against Antimicrobial Resistance (AMR) COM/2017/339. Online at: http://eur-lex.europa.eu/legal-content/EN/TXT/?uri=COM:2017:339:FIN

 

John F. Ryan

Co-chair (TATFAR)

Director for Public Health, Country Knowledge, Crisis Management

Directorate General for Health and Food Safety

European Commission

John-F.Ryan@ec.europa.eu

Tweet @CDCgov

https://www.cdc.gov/drugresistance/tatfar/index.html

Laboratory Supplies Directory - Now Live

LEAVE A REPLY

Please enter your comment!
Please enter your name here