This results in persisting infections in humans and animals which cannot be controlled. Because of this, various types of medical interventions such as surgery, chemotherapy and stem cell therapy may become impossible. The development of new antibiotics might seem the obvious solution. However, most pharmaceutical industries do not see that a priority, because it is expensive and lengthy, often yields little to no profits – and more likely than not, a newly developed antibiotic will never even reach the market.
"We are therefore waiting for a huge crisis to happen," says researcher Nathaniel Martin, professor, and head of the Biological Chemistry department at Leiden University, the Netherlands. "That's why as academic researchers we need to be proactive in addressing the issue of antibiotic resistance (AMR). We know that some bacteria become resistant because they can produce enzymes that break down antibiotics. We are trying to tackle that problem by developing enzyme inhibitors that prevent bacteria from destroying the antibiotics and thus maintaining their antibacterial activity. Another approach our research team is using to overcome resistance is by structurally modifying antibiotics. In this way, the bacteria are exposed to a 'new' antibiotic to which they are not resistant. Now, several years into the research, we are testing how well these modified antibiotics cure infections in animals. This is still the preclinical phase, but the results so far are very encouraging. If we can show that these new antibiotics are safe and effective in animals, the next step is to test them on humans."
Partners who could hardly be further apart – yet have a lot in common – have united to fight resistant pathogens. The International Consortium for Anti-Infective Research (iCAIR) is based in Germany and Australia – separated by nearly 16,000 km as the crow flies. This has not stopped the research cooperation from achieving its objectives: the development of new agents against infections.
Educating professionals worldwide
Martin: "But there is more we can do to prevent an increasing number of bacteria from developing resistance. Educating every prescriber of antibiotics is high on the agenda."
Education and communication – these were the motivations for Molecular/Medical Microbiologist Maarten van Dongen, in coordination with twelve Dutch public and private organisations, to found AMR Insights in 2017. The information platform focuses entirely on combating the issue of antimicrobial resistance worldwide. "The subject already had my attention, but when my neighbour died of an infectious disease, and there was no antibiotic that could save him, AMR came awfully close. There is a lot of research and information being generated on antimicrobial resistance worldwide. And that amount of information makes it difficult to determine what is of interest to you and to keep abreast of the latest developments. In the Western world it might be possible with some effort, but in developing countries it is much more difficult or even impossible. AMR must be tackled now. I do not accept that millions of people will die because of that. Already each day around 800,000 people worldwide die, and according to the World Bank, AMR leads to extreme poverty in many places. But make no mistake, also in Belgium, Germany and Southern Europe AMR is much more common than in the Netherlands. This is because in the Netherlands we are cautious about prescribing and using antibiotics in humans and animals. When I became involved with an app that collects and ranks information on type 1 diabetes, I thought that a collection platform with information on antibiotic resistance should also be feasible."
About the platform
The online expertise platform AMR Insights informs, educates and connects experts from different disciplines worldwide. Symposia and innovation missions are organised, and people can subscribe to the free newsletters. These contain information for people from different sectors; professionals in the human, animal, food and environmental sectors can draw on the collected and tailored information that helps them in their daily work. Information on research such as the modification of antibiotics, which Martin's team is working on, is also available on the platform. In addition, more than 300 ambassadors including researchers, doctors, veterinarians and entrepreneurs in some 60 countries work together to represent AMR Insights in the workplace. All with the aim of keeping antibiotics available and effective and preventing AMR from further threatening our health and food safety. "During an (emergency) consultation, a broad-spectrum antibiotic is often used until it is determined whether it is a viral or bacterial infection and, in the latter case, what type of bacteria it is," continues Martin. "We need to be able to view and sequence the genome of bacteria more quickly to see which are resistant and to what. As progress is made in diagnostics, this should also allow a more targeted approach to the use of antibiotics."
According to the experts, prescribing antibiotics to humans too much and too often is only one of the causes for developing resistances. Another reason is that antibiotics are also used in animals. There are countries where animals are given antibiotics because they promote growth. These animals and their products are then eaten by humans, along with their antibiotic contents. Furthermore, antibiotics-laden wastewater from institutions like animal farms and hospitals, ends up in the ground water, which must be purified to prevent further accumulation. Van Dongen: "Good systems are needed to filter antibiotics and resistant bacteria from wastewater. To this end, AMR Insights, together with VIG and EWS, established the Dutch Consortium Antibiotics and Medicinal Residues from Water in 2020."
A major summit meeting in London, Great Britain, has seen politicians, doctors, scientists, farmers and other experts come together in a bid to tackle the growing global antimicrobial resistance (AMR) crisis. Among these experts was Dame Sally Davies, England’s Chief Medical Officer, who described AMR as a ‘problem without a face’ because most patients are not told they have a resistant…
Both Martin and Van Dongen believe that prevention of infectious diseases is one of the most important ways to prevent the fact that, within a few years, many antibiotics will no longer work at all. The reasoning behind this is that, if people and animals do not become ill in the first place, antibiotics are not needed for their treatment, and further resistance does not develop. Good hygiene plays a role in prevention and should certainly be highlighted. Another important weapon in this fight is Antibiotic Stewardship, which is crucial in monitoring the use of antibiotics in humans and animals.
The amount of unnecessary antibiotic use could be further reduced through better and quicker diagnostics and tests which indicate whether antibiotics need to be prescribed and, if so, which ones. And while the development of new antibiotics remains a factor, the search for alternatives such as phages is another vital strategy. These are viruses that selectively attack bacteria and render them harmless. Last, but not least, new techniques can be used to tackle AMR, such as the modification of existing antibiotics. "So there are plenty of possibilities," states Van Dongen. "And all this information must be made available worldwide to mobilise everyone in the best way possible to tackle the antibiotic resistance problem".
With sustainable funding, AMR Insights can go one step further to become a global information and knowledge platform with even more searchable informationMaarten Van Dongen
Asked about their outlook on the developments in the coming years, the experts remain optimistic, even though there is much yet to be done: "The information that someone needs must be easily available," Van Dongen stresses. "And that is different information for a veterinarian than for a general practitioner. As an independent platform, we offer that targeted information. Now, our income consists of project income, contributions for participating in events and from sponsors. The objective is to change from short-term, project-related funding to long-term, programme-related funding. Then we will be able to set and realise our own objectives. With sustainable funding, AMR Insights can go one step further to become a global information and knowledge platform with even more searchable information. Because clearly AMR needs to be addressed now."
Martin adds: "The path I see for five years from now is that there is still a lot to do. A lot of money is needed for further research and clinical studies. The twenty people in our group are mainly working on that. We find the modification of antibiotics looks very promising, but having that said, it is certainly not the only way to tackle AMR."
Dr Maarten Van Dongen is a Molecular and Medical Microbiologist. After attaining his PhD in Biochemistry at the University of Amsterdam, the Netherlands, he has worked for the international Pharma and Biopharma industry in the Netherlands, Switzerland, Finland and Belgium. As such, he has gained extensive experience as a (project) manager of complex, international projects. More recently, he has worked as an advisor for Dutch and international public and private organizations in the domains of Life Sciences and Innovation. As an advisor, Maarten was increasingly asked to lead projects in the field of antimicrobial resistance (AMR). In 2020, he took the initiative to set up the global AMR Insights Ambassador Network.
Nathaniel Martin obtained his PhD degree in 2004 from the University of Alberta, Canada, after which he performed postdoctoral studies at the University of California, Berkeley, USA. In 2007, Martin moved to the Netherlands where he started his independent research career at Utrecht University. In 2018, Martin accepted a professorship at Leiden University where he currently holds a chair in Biological Chemistry. In Leiden, the Martin group works on developing new molecular strategies to address antibiotic resistance. Which a firm foundation in bioorganic chemistry, the approaches used by the Martin lab include the design and synthesis of new antibiotics as well as developing small molecule inhibitors of different resistance mechanisms.