Call: AMR Networks/Working groups

4th call, 2016

Inhibition of antimicrobial drug resistance: Exploiting an old drug as a basis for inhibitory discovery (EXPLOIT)

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Antimicrobial resistance (AMR) is a serious emerging threat for patients and the healthcare systems. It has been anticipated by the Institute and Faculty of Actuaries in Britain that AMR has the potential to reduce Gross Domestic Product (GDP) by 3.5% globally and to kill an additional 10 million people by 2050, and as such the topic is of high importance to the public.

Completed project

Our working group will highlight the efforts made in the field by academics and industry alike and raise awareness on the urgency of action and proposes the use of an old nitrofuran drug for future development of potent antimicrobials by intense study of its use, potency, and the fundamental science behind its mode of action and resistance mechanisms. The inclusion of distinguished and prominent scientists in the field coming from different backgrounds will emphasize a multidisciplinary effort is needed to tackle the serious problem of AMR in a timely fashion.

Network partners

  • Klaas Martinus Pos, Goethe University Frankfurt, Germany (Coordinator)

This network includes 10 partners, please click on the following link to see complete network composition: Network composition Inhibition of antimicrobial drug resistance: Exploiting an old drug as a basis for inhibitory discovery (EXPLOIT)

The alarming increase in the numbers of infections by multidrug-resistant Gram-negative pathogens in the EU calls for new strategies and solutions to address bacterial resistance mechanisms. In response to a call from the Goethe University Frankfurt and the University of Birmingham, UK, researchers from both institutions held a 2-day workshop in March 2016 with the aim of designing new strategies and solutions to drug resistance mechanisms. This workshop identified that there is an unmet need for a new oral agent active against multi-drug resistant Enterobacteriaceae causing urinary tract infections (UTIs) including in the elderly. To further address the question of feasibility of such a research proposal, we proposed a new network group including researchers from the Birmingham workshop plus additional experts with skills in medical microbiology, pharmacokinetics, in vivo models, and drug discovery/development in industry.

We organized a two-day event. On the first day, a conference in Frankfurt was held including talks from the WG members and invited experts in the field, discussion and opinion sessions. On day two, a working group meeting was held to distil all aspects of the conference and to formulate a research programme which will be the basis of an application to a H2020 call. This event was followed by a meeting on September 28th, 2017 in Frankfurt. Here the Work Packages were defined for a proposed consortium, as well as identification of potential funding opportunities. Moreover, we selected members of the consortium to contribute to a special issue on nitrofurantoin, focussing on its mechanism of action, resistance, PK/PD, and

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Phage Forward

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Antibiotic resistant bacteria represent a major threat to public health and solutions to this problem require actions at several levels of society.

Completed project

This is particularly true for phage therapy, which was initially proposed in the early twentieth century. Following a period of worldwide expansion this treatment option became almost obsolete in western countries before finally being stopped. In France and Germany, phage treatments were still applied during the 70’s while in some eastern countries, especially in Georgia, Russia and Poland it was continuously and successfully used up to present.

The biology of bacteriophages (phages), the natural enemies of bacteria, is now much better known and scientifically described than in the past. However, some questions about the safety of phage preparations in the context of their production process and their reproducible efficacies require more intensive research and pre-clinical and clinical studies. Also the diffusion of appropriate documentation about phage therapy towards the public, the medical community as well as other various stakeholders is lacking.

Our initiative is to develop an integrated approach to overcome the hurdles that slow down the reintroduction of phage therapy as a regular treatment option and therapy concept for antibiotic resistant infections, focusing primarily on phage-adapted regulation, production and research-based awareness. To realize this, we aim at building on knowledge-based trust and several highly relevant recent publications that have been focusing on phage-adapted production and regulative requirements so that the tangible benefit becomes readily available for the patients who need it.

Network partners

  • Thomas Rose, Vrije Universiteit Brussel, Belgium (Coordinator)

This network includes 7 partners, please click on the following link to see complete network composition: Network composition Phage Forward 

Antibiotic resistant bacteria represent a major threat to public health. Phage therapy, the use of bacterial viruses (phages) to combat bacterial infections, is increasingly put forward as an alternative/addition to antibiotic therapy. However, the conventional medicinal product (drug) pathways are developed to cater for static drugs such as aspirin or antibiotics, but are less suitable for sustainable (evolving) page therapy products. As such, there are no phage medicinal products on the Western markets, and very few phages are available to conduct the necessary safety and efficacy studies. PhageForward’s aim was to overcome the hurdles that slow down the (re)introduction of phage therapy in Western medicine. In concrete, PhageForward facilitated a series of meetings, workshops and a scientific publication, which contributed to the awareness that there is a need for an adapted phage therapy regulatory framework and to the elaboration and implementation of such a regulation.

This lead to the implementation of a prototype phage therapy framework in Belgium, which is slowly spreading to other EU Member States such as France, Germany and The Netherlands.

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Network on quantification of veterinary Antimicrobial consumption at herd level and Analysis, CommunicaTion and benchmarking to improve responsible use (AACTING)

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his network aims at developping guidelines and describing best practices for data collection systems of antimicrobials usage (AMU) in food-producing animals at farm level, applicable for herd level antibiotic stewardship, including benchmarking and result-communication to stakeholders and risk managers.

Completed project

To achieve this first a SWOT analysis of all currently available systems will be performed. Based on this strong and weak parts of the different systems will be identified and used to develop “best practice guidelines” adapted to the country specificities. The implementation of these guidelines also aim an improving comparability between results from various countries/ sectors/ species. Additionally, the up-to-date information on all currently available systems and the developed guidelines will be made publicly available through an online platform. This will aid interested people from various backgrounds to easily gain a comprehensive image of the work done on quantification of veterinary antimicrobial use at the herd level. Moreover, the platform will function as a discussion forum, where ideas, knowledge and experiences can be exchanged and discussed. Finally, a conference will be organized to gather all interested people active in the field of quantifying Veterinary Antimicrobial Consumption both to promote the guidelines and online platform as well as to discuss further developments and challenges.

Network partners

  • Jeroen Dewulf, Ghent University, Belgium (Coordinator)

This network includes 25 partners, please click on the following link to see complete network composition: Network composition Network on quantification of veterinary Antimicrobial consumption at herd level and Analysis, CommunicaTion and benchmarking to improve responsible use (AACTING)

AACTING, the “Network on quantification of veterinary Antimicrobial usage at herd level and Analysis, CommunicaTion and benchmarkING to improve responsible usage”, stems from the recognition that antimicrobial usage (AMU), as the main driver for the selection and spread of antimicrobial resistance, should be reduced. To be able to target the highest users and evaluate the effect of AMU reduction measures and responsible use campaigns, availability of adequate AMU data is vital.

Many countries have set up, are in the early stages of setting up or are planning to set up systems for monitoring farm-level AMU data in food animals. Such data have been shown to be powerful tools for antibiotic stewardship, e.g., stimulating a more responsible AMU through benchmarking farmers’ and veterinarians’ AMU. Due to a lack of standardisation among the systems, in terms of collection and analyses methodology (e.g., units of measurement and indicators) and benchmarking strategies (e.g., different benchmark criteria for acceptable or problematic use), the produced outcomes are typically not comparable. Furthermore, countries or organizations setting up a monitoring system will experience similar challenges and choices to solve.

The AACTING project has developed guidelines with practical advises on setting up AMU monitoring systems and their application to guide antimicrobial stewardship. These guidelines are disseminated through the AACTING-website. The website also contains a searchable database of monitoring systems, allowing to look per country or per animal species for farm-level AMU monitoring systems, currently containing information on 16 countries and 29 AMU data-collection systems.

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Bridging the gap between exposure to AMR in the environment and impact to human health

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Exposure to antibiotic resistant bacteria in the environment (water, soil, air) will impact human health involving complex interactions between bacteria and humans. Our network of experts, and advisors, will explore and summarize available tools and study protocols to systematically quantify environmental exposures to antibiotic resistant bacteria.

Completed project 

Guidance will be given to standardise surveillance protocols and exposure assessments in order to increase current quantitative knowledge across borders. Detection methods and modelling approaches will be outlined on how to link exposure data and epidemiological data to health impacts from antibiotic resistant bacteria. This involves quantitative exposure assessments from environmental emissions, as well as model development for carriage, excretion, colonization, horizontal gene transfer and dose-response. This will provide guidance to funding agencies and researchers on how to integrate exposure assessments and human health impact assessment into surveillance programs, funding schemes and research proposals/ projects.

Environmental transmission routes will be prioritised for future human health impact assessment studies. White papers to define a toolbox of existing approaches, best practices for study setups, and to identify research gaps will be produced by the two working groups responsible for developing guidelines and protocols for exposure assessments and human health impact assessment, respectively

Network partners

  • Ana Maria de Roda Husman, National Institute for Public Health and the Environment (RIVM), Netherlands (Coordinator)

This network includes 15 partners, please click on the following link to see complete network composition: Network composition Bridging the gap between exposure to AMR in the environment and impact to human health

Antimicrobial resistance threatens prevention and treatment of an increasing range of infections. Circulation of antibiotic resistant bacteria (ARB) in the environment (water, soil, air) may significantly contribute to human exposure. However, information on exposure to ARB from environmental sources is scarce, and little is known about the complex relationships between environmental exposure to ARB and its health impact.

With the working group set up in this project, available tools and study protocols to systematically study environmental exposures to ARB and to evaluate the associated health impact have been explored and summarized. Approaches on how to link exposure data and epidemiological data to health impacts from ARB have been described. These include quantitative exposure assessment from environmental emissions, as well as model development for carriage, excretion, colonization, horizontal gene transfer and dose-response, also including epidemiological studies. The results can serve as guidance to funding agencies and researchers on how to integrate EA and human health impact assessment (HHIA) into surveillance programs, funding schemes and research proposals/ projects.

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AMR Rapid Diagnostic Tests (AMR-RDT)

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Antimicrobial Resistance (AMR) has become a global threat and rapid diagnostics are urgently needed to tackle this challenge.

Completed project

To identify barriers to the development, implementation and use of rapid diagnostics and propose a roadmap to future solutions we are launching AMR Rapid Diagnostic Tests (AMR-RDT) as a multi-sectoral, multi-stakeholder and interdisciplinary working group with global reach. It brings together over 50 key individuals and organisations from 15 countries worldwide that are active in the field of diagnostics and antimicrobial resistance. This unprecedented body of expertise and the access it brings to national and international institutions, and networks will amplify the reach and implementation of the working group’s outputs. AMR-RDT will concentrate on five overarching topics: Need & Target Product Profiles, Technologies, Development Roadmaps, Business Models, and Behavioural Change.

The working group will focus on human healthcare but also recognises the importance of One Health aspects. AMR-RDT is funded as a one-year project by the UK Medical Research Council under the frame of the Joint Planning Initiative on AMR (JPIAMR) and is coordinated by Till Bachmann at the University of Edinburgh.

Network partners

  • Till Bachmann, University of Edinburgh, United Kingdom (Coordinator)

This network includes 50 partners, please click on the following link to see complete network composition: Network composition AMR Rapid Diagnostic Tests (AMR-RDT)

Antimicrobial resistance (AMR) is set to devastate modern medicine if left unchecked. Rapid diagnostics are urgently needed that can quickly tell if antibiotics are needed and which ones to use. Many strategic initiatives and policy interventions around the globe promote the development and use of rapid diagnostics. Nevertheless, there is a substantial gap between the urgent need for rapid diagnostics versus how much they are actually used.

To identify barriers of development and implementation of rapid diagnostic tests, the Transnational Working Group AMR Rapid Diagnostic Tests (AMR-RDT) was formed in 2017 from about 50 expert stakeholders and funded through the Joint Programming Initiative on Antimicrobial Resistance. This expert group has developed three major guidance publications in 2017/18. These documents address 1) how to find out which properties new diagnostic tests need to have to be accepted by end users, 2) which aspects must be considered for new diagnostic product development pathways and 3) which behavioural change is needed so a new diagnostic test is used and achieves its impact on tackling the threat of AMR.

The Transnational Working Group AMR Rapid Diagnostic Tests had input to wider AMR diagnostic initiatives such as the UK Longitude Prize on Antibiotics and the Innovative Medicines Initiative and plans to continue contributing to the global fight against AMR in the future.

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BEAM Alliance

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The growing risk of multi-drug resistant bacteria is a global public health crisis recognized by many governments; therefore, to combat the spread of resistant-bacteria and superbugs, new antibiotics, or alternative therapies must be developed. However, the financial attraction for R&D investment from large pharmaceutical companies is lacking, therefore, innovation in this therapeutic area is predominantly steered by small and medium pharma companies.

Completed project

To tackle the obstacle that superbugs present to society expeditiously, new policies and R&D incentives are needed to stimulate development in the EU. As an answer to this urgent need, we have formed the BEAM Alliance. The BEAM Alliance represents 50 European biopharmaceutical companies (small and medium size (SME) from 12 European countries involved in developing innovative products to combat antimicrobial resistance in humans and beyond.

The Working Group objective is to produce a new position paper regarding establishment of economic incentives in order to better sustain the innovation efforts of small and medium biopharmaceutical companies. The Working Group will collaborate with the existing community of stakeholders dedicated to implementing tangible strategies, including the EC DG SANTE, the UK AMR Review, WHO and the DRIVE-AB consortium. The BEAM Alliance Working Group should thus allow for expression of a unique and unprecedented opinion from the European SMEs perspective.

Network partners

  • Florence Séjourné, DaVolterra, France (Coordinator)

This network includes 50 partners, please click on the following link to see complete network composition: Network composition BEAM Alliance (BEAM Alliance)

Project resources

BEAM Alliance project website

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The Antimicrobial Resistance in Intensive Care (AMRIC) Network: A global surveillance network to monitor the role of the ICU environment in the emergence of AMR; Phase 1 (AMRIC)

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The intensive care unit (ICU) treats the most seriously ill patients in the contemporary health care system. Because of pre-existing illnesses and a high prevalence of infection – both as an admitting diagnosis and as a complication of ICU care – up to 75% of ICU patients are exposed to antibiotics during their ICU stay, and colonization or infection with resistant organisms is common.

Completed project

Patterns of resistance vary strikingly around the world, however, suggesting that there are potentially modifiable factors that can be targeted to minimize the emergence of resistance. We will leverage the collective resources of the International Forum for Acute Care Trialists (InFACT), a global network of close to 30 organizations that conduct investigator-led research into the optimal care of critically ill patients, to design a geographically representative surveillance program to track antimicrobial resistance in ICUs around the world, and to identify environmental and practice-dependent risk factors that are amenable to change.

During this initial phase of the program we will conduct a scoping review to identify key data elements to include in this surveillance program, and to determine the simplest and most costeffective manner of capturing key data. In collaboration with InFACT programs to map global capacity for critical care, to define the denominator in international prevalence studies, and to define the incidence of severe acute respiratory infection treated within the ICU, we will develop a pilot network of ICUs to launch the Antimicrobial Resistance in Intensive Care (AMRIC) network.

Finally we will use the data from these initial activities to develop a business plan and to seek long term sustainable funding. The global challenge of antimicrobial resistance requires global solutions. By addressing the impact of a venue within the health care system that is a major user of antibiotics and a key reservoir of resistant organisms, and ultimately doing so on a comprehensive international level, we seek to support efforts to address a major health challenge of the 21st century.

Network partners

  • John Marshall, University of Toronto, Canada(Coordinator)

This network includes 7 partners, please click on the following link to see complete network composition: Network composition The Antimicrobial Resistance in Intensive Care (AMRIC) 

The development of potent antibiotics has enabled the unprecedented survival of patients with life-threatening bacterial infections. However bacteria are able to develop resistance to these antibiotics (antimicrobial resistance, or AMR), with the result that over time, their effectiveness is lost.

Many experts believe that we are facing a crisis: the loss of antibiotics as a therapy for infection because of the rapid development of AMR. Nowhere in the health care system is the concentration of patients with serious infection, and therefore the widespread use of antibiotics higher than in the intensive care unit. On a given day, half of all ICU patients are infected, and ¾ are receiving antibiotics. The ICU is a breeding ground for resistance, but also a powerful but under-used resource to study the factors that drive resistance. It is recognized that both the organisms that cause infection in critically ill patients and their sensitivity to antibiotics differ in differing parts of the world, suggesting that there are modifiable factors underlying these differences.

The Antimicrobial Resistance in Intensive Care (AMRIC) program seeks to develop a global, ICU-based surveillance network that will use international variability in patters of infection and resistance to identify factors that promote resistance and to design programs to limit these. AMRIC builds on an international network of ICU-based research networks – the International Forum for Acute Care Trialists (InFACT). We have identified country leads in 22 countries on every continent, and are completing analyses of global capacity and needs for such a study, as well as modeling its potential utility by pooling published data. We have further developed collaborative funding applications and a program to evaluate the role of ICU water sources in serving as a reservoir for resistant organisms.

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Appropriate use of antibiotics: the role of CAM treatment strategies

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Worldwide strategies to control antibiotic resistance and its consequences (mortality, costs) are being developed, but are currently insufficiently, as for example demonstrated in the unchanged European consumption rates of antibiotics during the last years (RAND, 2016).

Completed project 

Preliminary studies have shown that Complementary and Alternative Medicine (CAM) practices and hospitals have lower antibiotic prescription rates and lower resistance rates compared to conventional practices based on additional prevention and treatment of infections strategies.

In order to offer conventional physicians a safe and effective alternative to antibiotics and to reduce misprescribing and overprescribing of antibiotics broadly, the available practical expertise and scientific knowledge on CAM strategies must be explored and systemized. The working group will collect available information on the use of CAM strategies regarding the use and prescription of alternatives to antibiotics in The Netherlands, France, Germany, England and Switzerland. The Working Group will further focus on the development of an evidence and expertise based decision-making tool for (conventional) doctors and the implementation of this tool in the European countries.

Network partners

  • Erik W. Baars, University of Applied Sciences Leiden, Netherlands (Coordinator)

This network includes 9 partners, please click on the following link to see complete network composition: Network composition Appropriate use of antibiotics: the role of CAM treatment strategies

Project resources

Reduction of antibiotic use by IM and T&CM

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Consensus group on the design, analysis and reporting of antibiotic stewardship trials

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Overuse of antibiotic is a major contributor to increasing resistance to antibiotics. One of the tools to reduce the inappropriate use of antibiotics is by antibiotic stewardship. Antibiotic stewardship interventions prevent antibiotic misuse by influencing the prescription behaviour of doctors.

Completed project 

Research of antibiotic stewardship interventions are often of insufficient quality to demonstrate the safety of antibiotic stewardship. This is partly because it is unknown what are the best methods to design and analyse these interventions. We will establish a working group of experts on antibiotic stewardship and research design to determine the best way to design, analyse, and report antibiotic stewardship interventions.

The goal of the working group is to formulate recommendations in a research guideline on antibiotic stewardship studies. The guideline aims to improve the quality of antibiotic stewardship research, which will lead to more effective use of recourses of safe and effective antibiotic stewardship interventions.

Network partners

  • Marc Bonten, University Medical Center Utrecht, Netherlands (Coordinator)

This network includes 10 partners, please click on the following link to see complete network composition: Network composition Consensus group on the design, analysis and reporting of antibiotic stewardship trials

Antimicrobial resistance is increasing globally. One of the main instruments to counter the emergence of antimicrobial resistance is by means of antimicrobial stewardship. The goal of antimicrobial stewardship is to optimise antibiotic to reduce the selection for antimicrobial resistance by interventions that focus on changing the prescribing behaviour of physicians. In the past years, there have been many publications about possible effective stewardship interventions. However, the quality of published stewardship studies is low. As a consequence, the evidence base for stewardship interventions is weak and does not guide clinical practise.

As part of the working group we conducted a comprehensive systematic review of the stewardship literature to identify where the quality of stewardship studies is most lacking. In addition, we organised two consensus meetings with experts on both antimicrobial steward and study design to discuss which recommendations are needed to improve the quality of studies. Based on the systematic review and consensus meetings we formulated recommendations that will be published in a white paper with the goal to inform researchers about how to properly conduct studies on antimicrobial stewardship interventions.

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Flies (Diptera: Muscidae) and the spread of antimicrobial resistant bacteria

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It is now common knowledge that antimicrobial resistant bacteria can be transmitted via direct contact in health care facilities and the community setting. However, recent studies highlight the importance of alternative transmission routes, such as zoonotic spread or potential dissemination through environmental sources (water, food items). In this context, vector-borne transmission of antimicrobial resistance has rarely been investigated.

Completed project 

The spread of antimicrobial resistance through flies could be a challenge both in industrialized (e.g. livestock, production, global warming) and low-middle income countries (e.g. insufficient sanitary systems, immediate contact between humans and livestock). However, there is up to date very little evidence for a public health-relevant dimension of antimicrobial resistance and flies.

Our objectives are therefore (i) to conceptualise the role of flies in the transmission of antimicrobial resistant bacteria, (ii) to identify gaps of knowledge for future research agendas and (iii) to suggest feasible strategies of intervention in both high and low/middle income countries. Typically for a One Health approach, our topic is in the interface of the environment, animal and human health. Our interdisciplinary working group engages sectors and actors from various disciplines (i.e. veterinary medicine, medical microbiology, entomology and infectious disease, representatives from low and middle income countries).

Network partners

  • Frieder Schaumburg, University Hospital Münster, Germany (Coordinator)

This network includes 6 partners, please click on the following link to see complete network composition: Network composition Flies (Diptera: Muscidae) and the spread of antimicrobial resistant bacteria

‘Filth flies’ share their living environment both with humans and animals and can transmit pathogens between these groups. In our working group, consisting of microbiologist, infectious disease specialists, entomologists and veterinarians, we wanted to find out if flies can transmit antimicrobial resistant bacteria similar to enteric pathogens.

We systematically appraised all studies on this topic that have been published so far. The main results of our work that flies carry antimicrobial resistant bacteria, particularly in the livestock setting. The similar genetic background of bacteria from animals, humans and the environment suggest that flies could be effective vectors of antimicrobial resistance. However, it remains unclear to what extent flies are responsible for infections with antimicrobial resistant bacteria in humans and animals. We therefore suggest to develop further models of risk assessment and to scale up surveillance of antimicrobial resistance in flies.

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