#1 Antimicrobial Resistance (AMR) – introduction from CN and NL

The world is fighting two pandemics at the same time – COVID19 and the silent pandemic of antimicrobial resistance (AMR). AMR occurs when bacteria become resistant to antibiotics, making their infections harder to treat. In Europe, approximately 25.000 people die every year because of drug resistant infections. It is estimated that AMR will kill an extra 10 million people globally by 2050.

In this episode we will talk with Dr. Maarten van Dongen (02:10) of the European platform AMR-insights and Dr. Yonghong Xiao (33:28), professor of infectious disease at the Zhejiang University and co-writer of China’s national AMR action-plan. We will talk about the scope of the problem, which industries are involved in the issue, the most important strategies in halting AMR and in which fields we should collaborate internationally. 

[00:00:00.820] – host

Welcome to the first episode of Innovation Matters, a podcast organized by the Netherlands Innovation Network. This episode we’ll be talking about antimicrobial resistance and is broadcasted from Shanghai, China.

[00:00:30.140] – host

Today, we cover the topic of antimicrobial resistance, also called AMR, antimicrobial resistance happens when microorganisms such as bacteria change, when they are exposed to antimicrobial drugs, such as antibiotics. This makes the infections they cause harder to treat or even untreatable bacteria are becoming increasingly resistant to many antibiotics, and too few new antibiotics are being developed to combat them. The World Health Organization rebukes this lack of innovation when it comes to the antibiotic pipeline. We will talk more about how the economic model is failing for developing new antibiotics. In Europe, approximately 25.000 people die every year because of drug resistant infections. It is estimated that AMR will kill an extra 10 million people globally by 2050. Without new antibiotics, it will be increasingly difficult to effectively treat infections and procedures such as organ transplantation, cancer, chemotherapy and common surgical operations such as hip or knee replacement will carry an increased risk of untreatable infection. The antibiotic pipeline needs to be revitalized by stimulating innovation and driving sustainable use at the same time. Today, I have two guests who are both experts on the topic, tackling the issue from the Netherlands and China, respectively. Our next episode will also be dedicated to this topic. Then we will talk with researchers who all combat AMR from a different perspective. My first guest is Dr Maarten van Dongen, who founded an online platform targeting professionals from several fields who are all dealing with AMR welcome. Dr. Maarten van Dongen, could you please briefly introduce yourself?

[00:02:10.610] – Dr. Maarten van Dongen

My name is Maarten van Dongen, I am a medical and molecular microbiologist and after my study at the University of Groningen in the Netherlands, I did my PHD at Amsterdam University in biochemistry. I subsequently started working in the pharmaceutical industry and later on in the biopharmaceutical industry in several European countries. And after that I did a lot of consulting work in the domain of innovation and life sciences.

[00:02:43.430] – host

Maarten started focusing on AMR after being involved in a number of projects on the topic for several Dutch ministries. He discovered that a variety of sectors are involved in causing antimicrobial resistance, but that the professionals within these sectors are not always connected adequately. This often causes them to be uninformed, as they tend to only focus on curbing the problem within their field in order to improve intersectoral collaboration. He founded AMR Insights, a global information platform on AMR.

[00:03:12.180] – Dr. Maarten van Dongen

I took the initiative in 2017 to involve 12 Dutch organisations, including public organisations but also private organisations, to very seriously investigate the feasibility of a novel information platform entirely focused on antimicrobial resistance. So together with these 12 organisations, we took a few months to investigate if it would be feasible to set up an international information platform to inform professionals on antimicrobial resistance. And after a few months of this feasibility investigations, we jointly concluded that there was indeed a serious market for a global information platform. And we took the initiative to initiate AMR-insights. So that was actually the beginning of a very inspiring journey because having this information platform was already the very beginning of a whole sort of, well, nowadays global Initiative focusing on curbing antimicrobial resistance.

[00:04:24.470] – host

I checked the platform and even though it started only three years ago, it has already transformed to the most comprehensive platform on AMR globally. The unique feature of the platform is that it’s the only one that targets all sectors involved in the AMR problem. You say six major sectors are responsible. Can you tell me which ones?

[00:04:45.740] – Dr. Maarten van Dongen

Many people think that this is only an issue for hospitals and maybe for doctors, but in fact, we see that six different sectors are heavily involved. And there should also be clearly addressed when when you talk about informing professionals. And one is the the health care sector, obviously, with the medical doctors, nurses, infection prevention specialists. So the all human health care sector, which is obviously a very important sector, the second very important sector is the the sector of animals with veterinarians, but also with the cattle farmers in this sector. Also, many professionals are involved, including what I mentioned, the veterinarians who should be aware of the developments should be aware of, well, that the threat of antimicrobial resistance, the third important sector is the agrifood sector. I mean, this is something which which many people do not realize, but also in the food sector, many antimicrobials, antibiotics are being used. So resistance is also a critical issue in this sector. And this applies, for instance, to the dairy sector and to the milk and the milk products, but also to the meat sector. Then we have the the sector of the what we call surveillance professionals and think of national and international authorities, but also NGOs and organizations like WHO. Also, these people are very much involved in antimicrobial resistance that obviously do need to very different information than, for instance, veterinarians. Then we have the sector of the innovators and I think of academia, universities, research institutes, but also academic medical centers and also certainly the the the research and development organizations or big pharma companies, small biotech company startups, diagnostics companies. Also, these organizations are dealing with antimicrobial resistance, but in an entirely different way compared to, for instance, doctors or veterinarians. So also these professionals need a different type of information. And then last but not least, we have the environmental sector think of water treatment plants, but also drinking water companies. I mean, these organizations are also dealing with antibiotics in wastewater systems. Antibiotics in the effluence of hospitals. And this is adds to the threat of AMR, of antimicrobial resistance. And so also the professionals working in this sector should be informed and should be involved.

[00:07:32.050] – host

So the platform collects all information on AMR, then selects all relevant materials for the specific sectors involved and then redistributes this information, right? That’s correct. If you if you read about the topic, you’ll notice right away that the main shortfall is data collection. Data is scattered among several sectors, research institutes, but also pharmaceutical companies that decided to discontinue their research activities, startups that have gone bankrupt, et cetera. And this all makes it unnecessarily complex to find solutions. So improved data collection and management is crucial and in my opinion, one of the strategies to curb AMR. But what other strategies should be followed as well?

[00:08:15.580] – Dr. Maarten van Dongen

Well, I fully agree with what you’re saying that data are of utmost importance. Data are, well, play an increasingly important role when talking about solving AMR, solving antimicrobial resistance. Basically, we as AMR-insights see five different strategies, five key strategies to curb and to fight antimicrobial resistance. And I will just briefly explain these key strategies. The first and by far the most important strategy is to actually prevent infectious diseases, because if you prevent people from becoming sick and also animals from prevent from becoming sick, then these people and these animals do not need antimicrobials, do not need antibiotics. And this means that also there’s no risk that you get resistant bacteria which are not sensitive anymore to antibiotics, prevention, better prevention can be obtained, for instance, through better hygiene measures, including washing your hands more frequently, but also, for instance, by vaccination, by having proper vaccination strategies such that people simply do not become sick.

[00:09:39.820] – host

So strategy number one is infection prevention, which is very obvious, personal hygiene is key here. And I think because of covid, there is more awareness of the importance of it. So if we could sustain the higher level of personal hygiene collectively, this would actually contribute to curbing AMR.

[00:09:58.560] – Dr. Maarten van Dongen

I fully agree, fully agree.

[00:10:00.670] – host

So strategy number two.

[00:10:02.770] – Dr. Maarten van Dongen

Well, the strategy number two is to have a better antibiotic stewardship and I will explain what is what this means is it is very important that the medical doctor, but also the veterinarians who do prescribe antibiotics and other antimicrobial products, that they do this, that they do so in a very careful way and that there is no irrational use of antimicrobials, that both by the medical doctors and by the veterinarians, it seems, or the evidence that in daily practice, antibiotics are being prescribed in many cases without proper testing, and this should be prevented to the extent possible. In addition, there is also this is related to antibiotic stewardship and there’s also a lot of the unwanted release of antibiotics and other antimicrobials in wastewater streams and effluence from hospitals and also in production plants. So this is also a way through which antimicrobials come into the environments and also will result in antimicrobial resistance. So actually, antibiotic stewardship has two sides of the coin. One is to have a better prescription, better and rational prescription of antibiotics to patients and to animals. And second, that there is a better control of the release of antibiotics in our wastewater streams and affluence of hospitals and in production plants throughout the world.

[00:11:39.510] – host

You say a lot of the antibiotics are prescribed without testing. Do you mean the need to test whether or not an infection is caused by a bacteria or a virus?Or are there also additional tests that should be conducted?

[00:11:53.850] – Dr. Maarten van Dongen

That is one of the three important aspects of a better testing and in fact, the better testing and improved diagnostics, in fact, also the third key strategy to curb antimicrobial resistance. It has, what I just said, three major aspects to this. One is to test for is this patient having a bacterial infection or does does the patient have a viral infection? Because many medical doctors do not realize that antibiotics do not work against viruses. So it is of crucial importance that it is known if the patient does have a bacterial or viral infection, and that means sometimes that you need to test. The second thing is, if you are if you know that it is a bacterial infection, it is of importance to know what bacteria is causing the infection, because not all antibiotics do work against all bacteria. So you need to know which bacteria is causing the infection. And thirdly and that’s of increasing importance, it should be known also to what antibiotics, the bacteria is already resistance and that bacteria can be resistant, can be sensitive to all available antibiotics, but they can also be and become resistant to one antibiotic, but also to two or three or even more or even to all commercially available antibiotics. So the prescribing doctor or the prescribing veterinarian should in fact know before prescribing the antibiotic to what antibiotics the bacteria which is causing the infectious disease is already resistance because then he knows what antibiotics to prescribe. So Improved Diagnostics is the third and important pillar in the global curbing of AMR.

[00:13:55.710] – host

So Improved Diagnostics, which is strategy number three, requires testing with testing you mean sampling the bacteria that is causing the infection. So a more informed decision on how to treat the infection can be made, right?

[00:14:09.810] – Dr. Maarten van Dongen

Yeah, yeah, yeah. And that has two two aspects. One is identification of the bacterium and two, identification testing. Or if the bacterium is susceptible, sensitive or already resistance to the antibiotic, well, to be prescribed.

[00:14:28.950] – host

So what about research and development for those tests? Because as far as I know, when I go to see my family doctor for an infection, I simply get antibiotics without any testing in advance. Are there accurate, fast and cheap tests out there or being developed? And also, what kind of technologies like artificial intelligence, for example, could play a role in this development?

[00:14:53.550] – Dr. Maarten van Dongen

A lot is going on when it comes to developing novel antibiotics. Many novel, types of diagnostics are being developed by, in academia, but also by many startups and small and medium sized enterprises around the globe. And that’s the good news. Obviously, many entirely different technologies are being tested and applied to these diagnostic tests. I must say already that it is not an easy task for these companies also to to validate these technologies, because it is quite difficult for them to, to well, to enter these tests to an existing health care centers and hospitals and to be able to test these new novel diagnostics, because obviously validation is of great importance. That’s in daily practice, quite a challenge for these companies. But coming back to your question, what is going on with different technologies and artificial intelligence is one of the upcoming and promising technologies when it comes to developing novel diagnostic tests. And, for instance, artificial intelligence can be used to better predict, predict drug resistance. It can also be used to better predicts the minimum inhibitory values for the antibiotics, but also to identify biomarkers and identify a resistant genes in the bacteria, but also for gene prospecting. And having said this, you can already conclude that because artificial intelligence is so broadly applicable already only within this small domain of diagnostic testing, that it it is obvious that we need to, well, sort of further streamlining of the use of artificial artificial intelligence. In order to avoid that, we will have many different type of applications because ultimately we would need to integrate data. We need to come to some unity. And in thinking where it comes to anti, uh, artificial intelligence.

[00:17:28.400] – host

Still, most AI solutions are premature and are in a premature state. Most of the new technologies are also only applied in the academia or at startup companies, but they’re not yet utilized at a large scale.

[00:17:43.400] – host

In our next episode, we will go more in depth as we’ll talk to several researchers in the field who are all tackling the issue with different tools and from a different angle. We’ll talk about understanding and predicting evolution paths of bacteria, the importance of big data collection and artificial intelligence. We’ll also talk about how technologies are used to develop new antibiotics and alternative treatments and how we could inhibit the resistance mechanism of bacteria. You will find the second episode to be released on this platform two weeks after the publication date of this episode.

[00:18:23.090] – host

I know that a AMR insights, your platform, also underlines the importance of applying new technologies.  On the website I read that last year AMR Insights hosted a matchmaking symposium on, quote, upcoming data technologies to corner AMR.  Next to artificial intelligence, other technologies were mentioned as well, like block chain technology and Internet of Things. I read about the topics discussed back then, and there are many promising developments out there, and if you think about it, there must be a great potential when these technologies will be unified. So we have these advanced insights already. We have improved tests, we could already prescribe medication much more efficiently, but for some reason it’s hard to get these technologies to use on a large scale. Apparently, these often startup companies face obstacles, bringing their product to the market. So what are the obstacles these companies face?

[00:19:28.640] – Dr. Maarten van Dongen

They face a number of obstacles to start with, and they also talk about the value chain of novel diagnostic, most ideas for novel diagnostics arise from basic research at universities. And this is obviously often subsidized or funded research, which is great. Then novel ideas come up, but to further develop the ideas to concrete applications. And this means and in practice to, well, pilot test systems. And once you have these and these startup companies can show that these tests may be effective and may be applicable, then these tests need to be well tested at a large scale, just then more money, more funding is needed for these large scale testings. And obviously these tests systems need also to be tested in real life and in hospitals and health care settings. I think that is by far the biggest hurdle because first of all, many different tests are being developed. I mean, there’s a whole broad scale of novel tests being developed that obviously is good news. But the problem is that all these tests need to be validated and hospitals are not the will not really set up to well, to provide testing possibilities for novel tests. And implementing a novel test system means also that you need to change the logistics. And so you need the input and help of all the professionals involved, including the doctors. And they may need to deliver the the blood samples and different test tube. As an example, the logistics may be different. Equipment needs to be changed, the data processing needs to be changed, the data integration need to be changed. So it is and it is quite challenging to actually test and validate these diagnostic tests in hospitals. And it is obviously needed to ultimately prove that these novel diagnostic tests are valid and could indeed be commercialized at a large scale and implemented at the global scale.

[00:21:42.820] – host

So the issue mainly concerns product validation and the lack of access to the infrastructure you need for clinical testing. But up to now, we were talking about companies working on products to improve diagnostics. So working on tests. But what about companies researching new antibiotics or alternative treatments? Do they face similar issues? Because what these companies try to develop is a solution for a severely pressing issue that the whole world is facing. If they would be successful in finding a new drug or alternative, the demand for their product would be insatiable. And it’s hard to believe that they would also suffer from similar issues due to their small scale effects.

[00:22:31.000] – Dr. Maarten van Dongen

You are now touching upon the fourth key strategy, which is needed to to curb antimicrobial resistance. And it’s the need for novel antibiotics and other novel antimicrobials to briefly elaborate on that. First, it is known that many bacteria around the globe are already resistant to existing commercially available antibiotics. There is a desperate need for novel antibiotics and other antimicrobial products. And one would indeed say, like you already mentioned, well, if there is such an enormous need for novel antibiotics and other antimicrobial products that it will be, well, a very lucrative business to well, to develop these and commercialize these, but in daily practice, in reality, it is a well, extremely challenging to start a company focused focusing on research and development of novel antibiotics and other antimicrobial products not only too well to develop these products, but to  ultimately, especially to commercialize these novel antibiotics. And this is also for AMR insights the reason to organize a webinar a few weeks ago where we invited Dr. Ryan Cirz as he was the co-founder of a United States company called Achaogen. This startup company was able to research and develop one, and at a later stage, even more antibiotics and also commercialized antibiotics. But despite having a antibiotic on the markets, this company went bankrupt after a short period of time. So we invited this co-founder, Dr. Ryan Cirz, to explain in this webinar why this company, with a promising antibiotic nevertheless went bankrupt.

[00:24:41.300] – Dr. Ryan Cirz

 And so really, the failures we’re seeing with the public companies, again, all my opinions, not the opinions of the entities I’ve represented in the past, is that this has always been the case. We’re just seeing it laid to bear in the public markets because the small companies don’t have the revenue from their other products to basically cover up this giant hole we’re about to talk about.

[00:24:59.130] – host

This was Ryan Cirz, founder of the antibiotic development startup Achaogen, he explains during a webinar on AMR Insights why it’s nearly impossible for a startup to develop a new drug.

[00:25:10.830] – Dr. Ryan Cirz

And so it’s not particularly complicated equation. So basically our argument is the cost to do business is much greater than the price you can charge for your product times the amount of times it gets used. That’s just the fact at every launch, the fixed costs do business. We’re really trying to be reductionist and get to core things that are really hard to argue with because of course, you can blow this away and add all kinds of bells and whistles and have a huge team. We’re really trying to get to the core issues in the business that are right there as you approved.  The limits on pricing, there’s lots of articles on that and where we’re sort of stuck there and then the limited number of patients we’re trying to get there before the problem is cataclysmically bad. But the math doesn’t work at that point in time. And then, of course, hopefully when we finally fix this some day, the issue that the most rare things, there’s no mechanism to get better reimbursement for something super rare. So today, an oral drug for ESBL UTI is more economically valuable than an I.V. drug for Acinetobacter. It just is. So how do we fix these problems? And they’re all driven by a number of patients and price.

[00:26:12.450] – host

The development of a new antibiotic takes often more than 10 years and can cost more than one billion U.S. dollars. And after investing the time and money, there is no certainty your product will turn out to be a successful antibiotic. It is a costly, risky and lengthy process. And even if you’re successful product reaches the market. There is another problem.

[00:26:35.930] – Dr. Maarten van Dongen

New antibiotics which have come on the markets, well, should preferably be kept on the shelf to the extent possible, because if we would allow these novel antibiotics to be distributed to the extent possible, then we would see that also for these new antibiotics, many bacteria would become resistance on that turn. And so we prefer to keep these novel antibiotics and reserve for already the very worst cases where patients will actually almost, well, nearly die. And this is sort of a last resort antibiotics.

[00:27:17.510] – host

This very low return on investment of the development of new antibiotics is probably the reason why big pharmaceutical companies hardly conduct any research in this field.

[00:27:28.880] – Dr. Maarten van Dongen

Exactly.

[00:27:29.690] – host

So what about other alternative treatments? When all antibiotics fail, phage therapy could be a solution. Phages are viruses that solely kill and selectively target bacteria, but there are other alternatives as well. Is that right?

[00:27:45.710] – Dr. Maarten van Dongen

That’s right. What you’re saying is that, well, alternative anti microbial strategies is in fact the fifth key strategy to curb antimicrobial resistance. It’s of key importance. And fortunately, many new technologies and many new products do arise, which are a very promising alternative to the use of antibiotics, especially also because it seems that to many of these alternative strategies, there’s no antibiotic, there is no resistance. Coming up, you’re mentioning phage therapy as one of the examples of alternative antimicrobial strategies. And from my perspective, phage therapy is an undervalued alternative to antibiotics. And phages are viruses. And these phages have the advantage to say that they do attack bacteria whilst not attacking human cells. So they are not dangerous in principle for for humans or for animals when you apply to animals so they can be used to to treat humans with bacterial infections because these phages do detect the bacteria whilst leaving the human body unattacked.

[00:29:06.440] – host

Are there any other important technological developments at the moment?

[00:29:10.930] – Dr. Maarten van Dongen

Yeah. What I also would like to stress is the use of novel nano materials and other tech materials which can be used, which have an anti microbial function. And as an example, you have novel materials which can be used, for instance, in hip replacement therapies, but also in bone replacement, other bone replacement therapy. And these novel materials have an anti microbial action. So in this case, it’s not needed to use antibiotics to treat patients when they have these replacements by these materials. In addition, there are also many upcoming genetic technologies like CRISPR CAS, and these are obviously, mostly used to, well, to identify and to to change bacteria. This is a very technical, technical story.

[00:30:08.450] – host

Our next episode will be more technical as we will discuss some technologies and research more in depth than we do now. So let me briefly summarize what we have discussed thus far. We’ve spoken about the six professions and industries that are in one way or the other affected by AMR and the five strategies how to fight and prevent it. AMR insights is a Dutch initiative and it’s serving a global audience. And I would like to zoom out to a global scale as AMR is a issue that crosses all national borders. Is there currently a global action plan or are there global guidelines in curbing AMR? And are all stakeholders, so institutions and countries, including China being a key player, are they all involved in this?

[00:30:55.430] – Dr. Maarten van Dongen

When talking about antibiotic stewardship and daily practice. It turns out that the regulations are there in some countries and there’s no unity when you compare the, the different hospitals. It’s is sometimes at a ad-hoc basis there are some well, in some cases national guidelines, also some international guidelines and recommendations by the WHO. These guidelines also are being included in the national and the international AMR in the global AMR actionplan. And also in the national AMR actionplans, but in daily practice, these regulations are not always yet implemented, so let it be that these are rules strictly followed. And in order to implement these these these guidelines, effectively, you need the involvement of many professionals. It’s not only the medical doctors who should stick to the regulations, but also the professionals in these health care centers and these nursing homes in these hospitals and these and these practices. And so in daily and daily practices, there is it’s it’s only partly implemented. And there are certainly not yet any sort of unity in thinking and unity and working and not at the national scale. Let it be at an international scale.

[00:32:29.280] – host

So instead of a global action plan, we have several action plans at national levels. So let’s shift our focus here to China. I ask about China because China is among the world’s largest producers and consumers of antibiotics, which are mainly used for disease treatment in humans and livestock. And China is also hit hardest by antibiotic abuse and therefore bacterial resistance. However, to control AMR, the Chinese health administrative authorities have taken a series of actions over the past 10 years, including the development of a national action plan in 2016. Dr. Xiao, who is here as well to talk to us, has co-written this national strategy. Professor Xiao is vice director of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases at the College of Medicine of Zhejiang University, Hangzhou, China. Welcome, Professor Xiao. Thank you for being here. Would you please introduce yourself briefly?

[00:33:29.140] – Dr. Yonghong Xiao

I’m a doctor Yonghong Xiao. You’re from the Zhejiang University. I’m also a professor of infectious disease at the first the hospital of Zhejiang university and worked as an infectious disease doctor for more than 30 years. And my major interest is the antibiotic resistance. So during the past to about three decades, I conducted some study, such as the surveillance of a resistance and also some study of the resistance to make Currentzis of the bacteria from the clinical settings. And also I did some more because to promote the rational use of antibiotics in the health care settings such as the hospital, the primary health care institution. So and I also conducted some education training for antibiotic management. So the major achievement during the past 20 years by a participant is a draft of some regulation and the orders issued by the Minister for Health, such as the administration, regulation for the antibiotic use. And also about four years ago, 2016, I drafted to the National Action Plan to contain AMR in China. So I think my major interest is AMR control in China and also do some study and cooperation with the government and also with some international cooperation with some other countries, such as the Netherlands, Sweden and Great Britain and so on.

[00:35:14.950] – host

You are the only Chinese ambassador of the AMR insights platform. Can you tell me why you joined as an ambassador? And can you also tell me to what extent the Chinese government stimulates international collaboration?

[00:35:28.990] – Dr. Yonghong Xiao

Yes, very interesting question, because I know AMR is a global health care crisis. That means that if we should to contain AMR we should have a wider international cooperation. That is AMR infectious disease resistant bacteria can spread by the human being’s immigration or some communication of the, and the transplantation and so on, so if we will the human beings hope to get victories over the control of AMR we should it take some international cooperation. Also, the international corporation is encouraged by the WHO, about the 2015, the WHO also issued a global action plan to contain AMR, one of the major strategic issues, the international cooperation that is in times also in China, in a global, in the national education plans of China to contain AMR. Also, the international corporation was right in the action plan. So I think we should need more and more international cooperation in the future. And also sometimes AMR insight is very, very interesting platform to promote the international cooperation in AMR control. And you can find the many, many ambassadors from different countries, different areas, who can find ambassadors from the Europe, from America, from Africa, from Asia. It’s true that at this stage, I am the only one from China, but I think the ambassador have a task to promote to the AMR control, while also promote the international cooperation. And also I will make use of the AMR insight platform to find more and more persons to join the AMR insight from China.

[00:37:22.900] – host

So the AMR topic is included in China’s national education plans. And these plans also call for the need for international collaboration. Can you tell me more about the main strategic points of this national action plan and in which fields is international collaboration stimulated in China?

[00:37:45.010] – Dr. Yonghong Xiao

Yes, but personally I think many kind of the field could be collaborating with other countries, for example, research and education and treaty and some others. But I think the most important thing is that we should have some international cooperation is a AMR surveillance, because we must get our  numbers, to manage the resistance around the world. And so we should get international cooperation in AMR surveillance and to get information about the resistance situation in different areas. And, by the AMR surveillance, we can find the spread of resistance between different areas. So after that, until we can make some decision to take some actions to control the spread of resistance, I think that’s what allows them to the international cooperation, because sharing experience, because, as you know, the education, uh situation in a different area, a different country is some difference. For example, in the Netherlands, the antibiotic use, is a relatively lower in comparison with China. So we can learn the experience of the Netherlands on how to decrease the antibiotic consumption and in the hospital in animal feeding and some other fields. And also sometimes during the past 10 years, in China will also take a very strict actions to control the irrational use of antibiotics in  hospitals. So we can found during the past 10 years, we got a very, very, very successful achievement in the antibiotics use in the hospital. So maybe our experience can be shared with other countries with similar health care systems. So I think that the the international cooperation is very important to see our experience of different countries, different areas, maybe can everybody can learn something from our country and experiences. And also the success stories can be implemented in some other country areas. I think it is very important that we should have some cooperation in the innovation study of the control of AMR, as you know, at the various stages almost where it lost the last chance to have a very powerful antibiotic for the pandrug resistant bacteria such as carbapenem resistant Enterobacteriaceae is a great challenge. Not only to China, but some other countries also have these problems. So if we have some cooperation in the new drug or new technology development, maybe you can find some useful major drugs or some other strategies to control the drug resistant bacteria. I think that’s my personal idea about a very important international cooperation field.

[00:40:54.800] – host

So international collaboration on surveillance is key in your opinion and you say that further collaboration on innovation, so the development of new drugs and new technologies should be stimulated as well? It’s interesting because for our next episode, we invited a Dutch researcher who’s developing a test which can measure the level of antibiotics in our environment. And this test is accompanied with data collection activity. And therefore, he’s starting a business, a data business in China to track the pollution levels in the environment. But so far, for the next episode, back to the back to the surveillance, how encompassing is China’s current surveillance system?

[00:41:37.340] – Dr. Yonghong Xiao

To my knowledge, we have some surveillance system just for the healthcare systems and also animal use of antibiotics that means, in agriculture and health ministers. You can find that we have both a mnister running the surveillance system for the antibiotic consumption and also AMR in human beings and also in animals. But to my knowledge, I did not found any surveillance systems for the antibiotic pollution in the environment. So but in fact, there are some studies of very small scale study about the antibiotic risk in the environment in the river, in the lake, in the land, some so on. So I think maybe in the future we should have some surveillance system to track the antibiotic residue of antibiotic resistant bacteria, see the environment as it is very important issue. And because as you know, this is the years and more and more environmental researchers, it’s getting very interesting to the control of AMR especially the environment, for example, in our university, there is a research teams is very interesting to involve the study of the AMR genes environment. So I think maybe in the future, as more and more researchers will be involved in the AMR of the environment, and sometimes I think maybe the environment authorities will set up AMR surveillance and also antibiotic residue in the environment i think.

[00:43:16.080] – host

Surveillance has improved over the last years, but environmental surveillance is not there yet. So China has seen vast economic growth over the last decades, which of course is great, but has also worsen the situation of AMR. Agriculture, for instance, agriculture has changed from traditional small-scale approach to a more intensive animal farming, which requires a lot of antibiotic use. But also, like I said before, nowadays China is the largest producer and user of antibiotics in the world. So there are many challenges China has to tackle. 2016 was a tipping point as this was the year the National Action Plan was initiated. Could you tell me what China has done thus far?

[00:44:06.600] – Dr. Yonghong Xiao

OK, as you know, the antibiotic consumption could be found in the health care city, also animal feedings as it’s the same in our country and about two years ago, the antibiotic consumption in the hospital is very, very high. So you can find ten years ago the hospitalised patients used antibiotics over 60 percent. That means that more than 60 percent of their hospitalised patients receive antibiotic treatment during this stay in hospital. And from 2011, the minister of health of China take a very strict management about the antibiotical use in the hospital and set some target for the hospital, that means, the hospital must meet with the target to within a very short time, for example, one to two or three years. So up to now you can count the antibiotic consumption in the hospital have a very sharp decrease. You see, for example, the antibiotic use rate in hospitalised patients is forty five percent now, that is, decrease from 70 percent to 40 to 47 percent and so is a big decrease. And also you can find the out-patient to use of antibiotics, also have a bit of a decrease. So in the hospital is patient in that hospital, for example, X Hospital and X hospital. The antibiotic use is getting more and more reasonable. But it’s true that the primary health care setting, for example, is some city clinic or the countryside. It can indicate to antibiotic use have some problems. Maybe the future of the government will take some action to control the use in the primary system. So I think in health care settings, the major strategies taken in China is the government administration, that means the government asks the hospitals to do something because in our country most of the hospital is a public hospital. Then, it’s over 80 percent of a large hospital belong to the government. So the hospitals always have a very good relation, with the order of the, the administrative authority. So I think you can found what was the reason why the hospital antibiotic consumption has a huge decrease during the past 10 years. Also in the same times, during the past several years, to my knowledge, the animal use of antibiotics also getting more and more strict control. During of about two or three years ago, the minister of Agriculture also issued a regulation, for example, forbidding the use of colistin as the growth promoters at animal feedings. So I think that’s good news. But the restrictions and a very careful situation in the animal sectors is not so clear for me because I’m not an agriculture expert, because I’m just a doctor so I can connect doctors. So I think in China the experience to get a success in antibiotic irrational control is the government is power. So I think as the government, to have a very strong powers to go in the irrational use of antibiotic use in both health care city and also an innovative setting after the decrease use your point about also you can found some resistant bacteria’s, have a trade to decrease gradually and very special that the AMR see them as a new resistant Staphylococcus aureus also decreased from 50 percent to about 35 percent, so during the past 30 years. So I think that’s a story of China of the past 10 years about the antibiotic use and to also AMR control.

[00:48:30.440] – host

What’s the current status of development of new medication, alternative treatments, new technologies, et cetera.? And is there a specific goal?

[00:48:40.640]

Yes, if you’re reading the National Education Plan to contain AMR that is in 2016, you can found to this every purpose of saying the National Education Plan. One is the development of new antibiotic and alternative therapeutic strategies which included so such as for example and phages and also some protein drugs and so on. So you can find a very set of targets to describe in the national education plan by the end of 2020 at the least, which would have to innovative drugs will be developed in China. To my knowledge, also the Chinese government have some of the science and development project managed by the minister of science and technologies. There’s a new drug, a mega mega project of the new drug development, which includes some project for the new antibiotic, which I think is the situation.

[00:49:54.020] – host

So two innovative drugs by the end of 2020, is that correct? By the end of this year. And is phage therapy one of these two to be developed treatments?

[00:50:04.820] – Dr. Yonghong Xiao

Yeah, found some researchers especially for example, from Shanghai and some other cities. Some researchers conducted a phages therapeutic for the pandrug resistant, for example, pandrug resistant Acinetobacter Baumannii. Also, those who come up are resistant to antibiotics. And but I think because the phages is also a virus and the bacteria virus, we should have some basic research about the possible use. In Europe also conducted phages study, to my knowledge, maybe we should have some study in the primary pre-clinical stage. We should we can to conduct some animal study and then we can use a phage in the clinic. Maybe I think we should have a relatively longer way to go. We’ll get into the final use of the phage in the clinic.

[00:51:06.560] – host

In order to wrap up what is the most promising solution for the problem and what are the most important steps to take, in your opinion?

[00:51:15.320] – Dr. Yonghong Xiao

I think to my opinion, my personal opinions. I think that the Netherlands is experiencing a very successful experience, I think, because you can found in the Netherlands the AMR is so bad. Resistance rate is very low. And in the same times what’s the reason of this result? The major reason is that the irrational use of antibiotics is, that means that in the Netherlands and also some other northern European countries, for example, Sweden and Denmark and some other countries that the antibiotic consumption is relatively small. So I think that while on the one hand we should promote their rational use of antibiotics, because the more antibiotic use is you’ll have a higher resistant level. That is if we lower the antibiotic consumption that means that the resistance level will be decreased. So I think that’s a balance. It Is is very important. So I think that any person is included, the doctors and nurses and the general persons can do his own jobs to promote the rational use of antibiotics. So I think antibiotic rational use should be the primary strategy to control AMR, because if we decrease antibiotic use, that means the bacteria can have a very, very less contact with antibiotics. The bacteria, will not convert to resistant germs so I think is very good, as the Netherlands is experiencing. OF course, on the other hand, we should have some new technology and new new drugs or some new diagnostic technic. And also we should find some new alternative therapeutic method to treat today patients. So if we have some more strategies to treat infected patients for them is antibiotic use will be decreased and also that bacteria will suffer from different treatments. Well, listen, that is I think we should have a two hands should be used.

[00:53:27.790] – host

Thank you, Professor Xiao, thank you for your time. I would like to ask the same question to Maarten van Dongen of AMR-insights.  Mr. van Dongen that we’ve discussed the five strategies how to combat AMR. In your opinion, which is the most important strategy or which one is the most promising or has the highest payoff?

[00:53:48.370] – Dr. Maarten van Dongen

Prevention has according to my gut feeling, the highest payoff. I think if. By preventing infectious diseases, we will be able to, well, avoid that many millions of people around the globe become diseased, get an infectious disease. And if we can prevent this disease, patients do not need antibiotics and do not desire treatment at all. So these patients do not deal with resistant bacteria, but it’s certainly not enough to focus only on preventing infectious diseases. So I think that by combining efforts and focusing all the five key strategies preventing antibiotic stewardship, better diagnostics, novel antibiotics and better and novel alternatives for antibiotics, I think only by jointly picking up all these key strategies, we may be able to well diminish the threats which are being well offered by antimicrobial resistance.

[00:55:05.010] – host

AMR insights is a unique platform, as we discussed before, but also partly because of its ambassador network, which is a broad network that is growing organically around the world. My question is, who are these ambassadors and how can you become one?

[00:55:23.320] – Dr. Maarten van Dongen

Yeah, the AMR insights ambassadors network was started last year in September, because we we realized that while many professionals around the globe are involved in curbing AMR, including what I said before, medical doctors, veterinarians, epidemiologists, entrepreneurs, journalists, professors, scientists working in public and private organizations around the globe. And we decided to start this network because we needed input from from people who were really working in the front lines, so to say, the boots on the ground. So we really anticipate and we we welcome their input. And at the same time, we also realized that as AMR insight, we want to have more output via these ambassadors. So these ambassadors also play a role in in in spreading the information we provide in the networks and their networks. So in effect, these are the capillaries from our insides, the lungs, so to speak. And so far we have now 170 ambassadors in almost 50 countries around the globe. We have set a goal to have at least one ambassador in each of the countries of the rest of the world by the end of this year. So this means in all the 180 countries we have in principle, everyone who is involved in curbing AMR and is interested to join can is welcomed at the network. I mean, addresses, simple form you have to complete. It’s online available on the AMR insights information platform. And by completing the form you you can you can enter that the network. We welcome professionals who are involved. We welcome especially those professionals who are really motivated and also inspired to add to the global curbing of AMR. And we have big ambitions for the network. We we recently started to set up a board for this network, which we are now with five people in this board from the .. And we we are working on the strategic plans for this network. We are working on setting our goals and how also we want to develop in the well in a and an important voice that when it comes to curbing curbing antimicrobial resistance at the global scale.

[00:57:52.890] – host

Thank you, Dr. Maarten van Dongen. And also thank you, Dr. Yonghong Xiao, for taking the time to share your knowledge and insights on how to tackle the problem of antimicrobial resistance. If you would like to know more about the topic, please visit Maarten van Dongen’s global Information platform www.AMR-insights.eu. If you are a professional in one of the fields that were mentioned at the beginning of the episode. Then you might want to connect to the platform to pass on and gain insights and share knowledge with others. Please feel free to share this episode and help spread awareness. If you want more information on the speakers, please visit our website NetherlandsInnovation.nl. Here you can also leave a comment. If you would like to reach us. Our email is China at NetherlandsInnovation dot nl, and our next episode will also be devoted to this topic. But then we’ll go more in depth. We’ll be talking about the importance of tracking antibiotic pollution in our environment and about current fundamental research and how it might offer solutions for the future. The next episode will be published in two weeks, and we’ll hope you’ll be tuning in again. Thanks for listening.