In June 2018, in cooperation with the Norwegian Institute of Public Health and other expert communities in Bergen, Stavanger, Oslo, Trondheim and Tromsø, TMF launched a research programme focusing on the AMR issues that the expert communities themselves prioritise. The response to this initiative was excellent. TMF received as many as 16 project proposals that international experts have assessed as being of high quality, while at the same time reflecting the breadth, strength and substance of Norwegian research on antimicrobial resistance.
In accordance with the experts’ recommendations, NOK 75 million was awarded to four projects. The projects, which will have a duration of four years (2019–2023), cover the three topics in this initiative: treatment, diagnostics and monitoring. Host institutions in Tromsø, Trondheim, Bergen and Oslo are engaged in the research. Universities coordinate three of the four projects, while Haukeland University Hospital will coordinate one project. Stavanger University Hospital, St. Olavs Hospital, Oslo University Hospital, the University Hospital of Northern Norway, Drammen Hospital and the University of Bergen are participating as partners. There are also some national partners, such as the Institute of Marine Research and the Norwegian Veterinary Institute. All the projects have international partners.
‘Paradoxically, antimicrobial resistance is partly caused by the health service itself. This is because incorrect use of antibiotics, for example where an antibiotic is used that does not “target” the microbe, is an important cause of the development of antimicrobial resistance,’ say Professors Elling Ulvestad and Harleen Grewal of Haukeland University Hospital and the University of Bergen. They are conducting research on methods for arriving at faster and more precise diagnoses of respiratory tract infections.
‘Pneumonia is one of the diseases where the use of antibiotics is too high, both in Norway and internationally. The reasons for this high consumption are that the disease is dangerous and that diagnosing it and identifying the pathogenic microbes involves difficult and time-consuming microbiology work. To ensure that patients recover, doctors therefore prescribe high doses of antibiotics, even for patients who do not need antibiotics. In the long term, this will prove to be a self-defeating strategy,’ Ulvestad points out.
The researchers will try to counteract the development of antimicrobial resistance by evaluating and developing new diagnostic tools, including a technological innovation – clinical metagenomics – which involves sequencing the genomes of the microbes. This could promote targeted and more correct use of antibiotics. In addition, the project will attempt to identify biomarkers that can help to indicate a prognosis for patients with pneumonia; endeavour to develop new diagnostic tools for identifying antimicrobial-resistant bacteria; optimise treatment protocols for pneumonia, and introduce new technologies that can help to detect and monitor antibiotic-resistant bacteria in people. ‘We thereby hope to make an important contribution to developing the knowledge we need in the fight against antimicrobial resistance.’
The project is being carried out in close cooperation with the University of Bergen and Drammen Hospital. The international research collaboration includes leading research groups in Denmark, the Netherlands and the UK.
In addition to reducing the use of antibiotics, it is important to develop new types of antibiotics that are effective against resistant bacteria and that can be combined with existing antibiotics. Under the leadership of Professor Marit Otterlei at the Norwegian University of Science and Technology (NTNU), an interdisciplinary team of researchers from the fields of microbiology, biology, chemistry and medicine is conducting research on several new antibiotics that can form the basis for the development of new drugs.
Marit Otterlei says that the knowledge on which the development of these antibiotics is based comes from basic research on the maintenance of DNA and what mechanisms the bacteria use to develop resistance to antibiotics, i.e. how they mutate. ‘These new antibiotic candidates attack bacteria in a completely different way from the antibiotics in use today, and they can potentially be developed into new antibiotics and be used to increase the effect of and counteract the development of resistance to current antibiotics,’ she says.
The project entails close cooperation between expert communities at NTNU, St. Olavs Hospital, Oslo University Hospital and Copenhagen University.
‘The project at the University of Tromsø, which concerns the bacterium Klebsiella, is an opportunity for an outstanding team of researchers to study this group of bacteria in greater depth. Klebsiella has a key role in the global spread of antimicrobial resistance, and it is a target bacterium for innovative diagnostics, monitoring and alternative treatment.
The World Health Organization (WHO) regards Klebsiella pneumoniae as a key factor in the global spread of antimicrobial-resistant pathogenic bacteria. WHO therefore classifies Klebsiella as a critically important target bacterium for research in the fight against antimicrobial resistance. The project is mapping the occurrence of and genetic relationship between Klebsiella in healthy and ill people and animals and in the environment in order to understand the importance of different reservoirs in the spread of antimicrobial-resistant pathogenic Klebsiella.
‘This could form the basis for new diagnostic methods and targeted monitoring with a view to preventing the spread of, and infections caused by, particularly important groups of Klebsiella. We are increasingly finding that we have no effective treatment alternatives against serious infections caused by multi-resistant Klebsiella. We will therefore also study the effect of bacteria viruses (bacteriaphages) on carriership and infections by antimicrobial-resistant Klebsiella as an alternative or supplement to antibiotics.
This a multi-disciplinary and cross-sector project. It utilises Norway’s unique infrastructure for monitoring antimicrobial resistance by using the Norwegian Surveillance System for Antimicrobial Drug Resistance (NORM), the Monitoring Program for Antimicrobial Resistance in the Veterinary and Food Production Sectors (NORM-VET), the Institute of Marine Research, the Norwegian Food Safety Authority and an established Norwegian and International network of researchers (www.nor-kleb.net). The project is being led from UiT – The Arctic University of Norway in close cooperation with Stavanger University Hospital, and it involves four other Norwegian institutions: the Norwegian Veterinary Institute, the Institute of Marine Research, the University Hospital of Northern Norway and ACD Pharma (business partner). The international research collaboration includes leading research groups at Karolinska Institutet (Stockholm), Monash University (Melbourne), Queens University (Belfast) and Institut Pasteur (Paris).
Under the leadership of Professor Jukka Corander at the University of Oslo, researchers in Norway and abroad are studying E. coli, a bacterium that often causes infections in the blood and urinary tract and that is now proving resistant to antibiotics more often than before.
The development of antimicrobial resistance is largely related to specific genetic variants (high-risk clones) in most bacteria species. These high-risk clones have now spread throughout the world.
‘If we are to succeed in stopping the development and spread of antimicrobial resistance, we have to increase our understanding of how and why such high-risk clones arise and are spread,’ says Professor Jukka Corander. ‘In this project, we will focus on Escherichia coli, which is the bacteria species that most often causes infections in the blood and urinary tract. The WHO has also defined E. coli as particularly important in relation to research on antibiotics and antimicrobial resistance.
‘In the project, we are taking a system biology approach in order to understand what lies behind the selection, evolution and spread of high-risk E. coli clones. The objective of the project is to develop a basis for future risk assessments of existing and new bacteria clones, to improve monitoring and diagnostics, and to study new potential treatment strategies to limit the spread of antimicrobial resistance,’ Corander says.
The project is a collaborative project with UiT – The Arctic University of Norway and the Norwegian National Advisory Unit on Detection of Antimicrobial Resistance at the University Hospital of Northern Norway. The project also cooperates internationally with research groups at the University of Birmingham, UK and Houston Methodist Hospital in the USA.
AMR-Bridge will make the research results from the National Research Program on Antibiotic Resistance (AMR) available to other researchers and to the general public.
“We will facilitate the recruitment and development of new research talents, arrange academic hubs and take on the role of a hub in both dissemination and in an international research network on antibiotic resistance”, says Arnfinn Sundsfjord, who leads the project. The project focuses on network building and dissemination and arranges, among other things, annual gatherings.
The Trond Mohn Foundation has, together with the University of Bergen, Haukeland University Hospital and Stavanger University Hospital, established the research center CAMRIA (Combatting Anti-Microbial Resistance with Interdisciplinary Approaches).
-The idea behind the center is that research on antibiotic resistance has largely been driven by medics and biologists. We want to connect knowledge from the social sciences, informatics and mathematics with medical knowledge to find out more about how and why resistance is spread”, says professor of infectious disease medicine, Nina Langeland, who heads the center: – The vision for the center is to engage researchers across disciplines and to use the entire population in Western Norway to find out how resistance is spread, and how to get health professionals, politicians and the population to come together to reduce unnecessary antibiotic use.
People’s attitudes to antibiotic use must also be included in the research at the center, and the Citizens’ Panel is part of the research group to study this in more detail. In addition to supporting the establishment of the center, the Trond Mohn Foundation will support 3-4 research projects linked to the center. Read about the establishment of the center and the announcement of the research projects here.
Programme period: 2019-2025
Total grant: 106 MNOK
The Bergen-led project
Title: The Impact of Molecular Point-of-Care Testing and clinical metagenomics on Antibiotic Stewardship for acute respiratory infections (RESPNOR)
Host institution: Haukeland University Hospital
PI: Elling Ulvestad
TMF-grant: 15,5 MNOK
The Trondheim-led project
Title: Targeting AMR by inhibition of bacterial stress responses
Host institution: Norwegian University of Science and Technology (NTNU)
PI: Marit Otterlei
TMF-grant: 20 MNOK
The Tromsø-led project
Title: Klebsiella pneumoniae – a key driver in the global spread of antimicrobioal resistance and a target for new approaches in diagnostics, surveillance and alternative therapheutics (KLEB-GAP)
Host institution: UiT – the Arctic University of Norway
PI: Arnfinn Sundsfjord
TMF-grant: 20 MNOK
The Oslo-led project
Title: Battling Pandemic Multi-Drug Resistant E. coli Infections
Host institution: University of Oslo
PI: Jukka Corander
TMF-grant: 19,5 MNOK
National cooperative project – AMR-BRIDGE
Title: AMR-BRIDGE – a common project to bridge and promote AMR-projects funded by TMF.
Host institution: University of Tromsø
Project leader: Arnfinn Sundsfjord
TMF-grant: 5 MNOK
Title: Combatting Anti-Microbial Resistance with Interdisciplinary Approaches – CAMRIA
Host institution: University of Bergen
Project leader: Nina Langeland
TMF-grant: 7,7 MNOK
Projects related to the CAMRIA center
TBD – autumn 2021
TMF-grant: 18 MNOK