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Background

Carl: From your professional clinical career in Singapore as well as your work with peers and colleagues across south and southeast Asia, can you describe how attitudes have changed towards the rise in AMR over the last few decades?

HLY: It has been almost 20 years since I first came upon the issue of antimicrobial resistance and I must say that things have changed a lot and mostly for the better. When I was just a young medical officer, we would prescribe antibiotics and not bother too much about antimicrobial resistance. We had limited understanding of what it was. Likewise, the public at that time had little concept of antibiotics let alone antibiotics resistance. One of the common refrains from doctors especially in primary care, was that their patients would ask them for antibiotics and if they did not receive antibiotics, they would not be happy. I think if you fast forward to today, all the different educational and promotional efforts that have been done, especially in the hospital setting, most doctors and healthcare professionals are aware of the issue of antibiotic resistance and the need to prescribe and use antibiotics wisely. Likewise, amongst the general public there is a greater understanding that antibiotic resistance is something real and something that they would want to avoid. In fact, many patients now go to the GP expecting that they would not receive antibiotics and their change in perception and attitude has been quite a major shift over these past 20 years.

Growth drivers

Carl: What have been the major growth drivers of AMR in South and Southeast Asia?

HLY: If you mean by this question what are the factors that have led to an increase of drug-resistant bacteria in this region, then I think there are 2 parts to it. The first is in human health and healthcare, as I mentioned before, we were using antibiotics relatively freely a couple of decades ago, and only recently have we been aware of the consequences and attempted to use antibiotics more wisely. So, this increase in the human use of antibiotics for healthcare reasons is one of the main drivers of the growth of antibiotic resistance. Unfortunately, because we will still continue to use antibiotics, that’s unnecessary parts of healthcare now and this is less likely to change. The other component involves the use of antibiotics in livestock. Several decades ago, scientists have discovered that if we were to give a little bit of antibiotics, a little bit everyday to animals, they grow faster, they become fatter and gain weight more rapidly and they can be shipped off to the market in a shorter period of time. This is called using antibiotics as growth promoters and that is still a major strategy for lots of the livestock industry, especially in Asia nowadays. I think if this is not changed, we will continue to see an increase in the rate of antibiotic resistance for the foreseeable future. I think is appropriate to take a step back and understand that antibiotic resistance is part of evolution. The bugs themselves evolve as we use drugs that attempt to kill them and that is true for whatever we do and how bugs have evolved over time. So, what we have done however is to use antibiotics in such vast and ever-increasing quantities that we have sped up the process of evolution and we have done this in 2 ways. The first is in health and healthcare. As I mentioned 20 years ago, we would have given antibiotics and not bothered much about antibiotic resistance and the general public will also ask for antibiotics. Although that has changed, nonetheless there is still quite a lot of antibiotics prescribed for infections and that is not going to change too much. In the agricultural setting, what people have found is that antibiotics are effective growth promoters meaning that if I were to give in bits every day to animals, they would grow faster and become fatter and they can be then sold at the market much earlier than if no antibiotics were used. And that I think has been a major driver of antibiotic overuse in countries where livestock breeding, and agriculture is a major part of the economy. So, I think the combination of these 2 major uses of antibiotics have been driving the rise of antibiotic resistance rates across the globe.

Antibiotic Access

Carl: Do you think across our region, access to antibiotics needs be more controlled and more restricted?

HLY: That is a very good question and I think it deserves a nuanced answer. In metropolises like Singapore, big cities like Bangkok and around Asia, making antibiotics prescription only for instance will help greatly to prevent the misuse of antibiotics. But in the rural parts of many countries, where access to healthcare as a whole is challenging and where people have to travel many miles just to find a doctor for instance, then making antibiotics prescription only would have consequences and this includes people not being able to access these life saving drugs should they need it. So, we need to have a more nuanced strategy where we are able to control the use of antibiotics or at least use them wisely without preventing the access to antibiotics particularly in rural areas where access to healthcare is poor. to such an extent that people will start to die from the lack of antibiotics.

Economic Impact

Carl: If the current AMR rates continue on this trajectory unabated, what do you perceived to be the major economic impacts to our region? Will it be possible to foresee a possible timeline for when those impact will happen?

HLY: That is a really difficult question to answer. Partly because we have had very little work done on the economic impact of AMR just for South East Asia or Asia alone. But several years ago, in 2016 the World Bank published a report that looked at what would happen in 2050 if current rates of increase in antimicrobial resistance were to continue. And their estimate showed that if we did nothing now, by 2050 the impacts of AMR on the economy will be equivalent to what happened during 2008 financial crisis.

COVID-19

Carl: From this year, we have seen the healthcare industry struggle to manage the COVID-19 pandemic with a new pathogen running around in this global pandemic. How has this affected AMR in our region?

HLY: I think in general the COVID-19 pandemic has been terrible for everyone. If we just look at it from the perspective of AMR, then it has been both good and bad. Good in a sense that people are now aware that viruses cause community infections including upper respiratory tract infections and therefore perhaps people will understand that not all upper respiratory tract infections will require antibiotics. So, I think that the COVID-19 has driven this message more forcefully than anything else we have done in the past with respect to community type infections. But it has been bad in a sense that everyone for the past 10 months now have been focused on COVID-19, all messages for all other diseases have more or less been lost and it has also set back the work of people who have been trying to educate others on antimicrobial resistance and trying to promote the concept of better use of antibiotics. It has just driven everything off the agenda, so, COVID-19 has been mixed in this regard where AMR is concerned.

Stewardship

Carl: What sustainable measures in our region have you seen to reduce antimicrobial resistance?

HLY: Currently I am afraid to say that has been very little of that. I think there are the beginnings of sustainable activity, including this drive to have antibiotic stewardship in the hospitals. Antibiotic stewardship is this concept whereby we attempt to guide healthcare providers especially doctors to prescribe antibiotics more wisely. To stop them if they are not needed and obviously not to prescribe them if obviously the patient does not have a bacterial infection. So, I think this has been driven by the World Health Organization and many hospitals in the region including in Singapore have adopted this. In the livestock industry, I think what would really make a difference is if we were to ban the use of antibiotics as growth promotors for animals. This cannot happen overnight, and it cannot happen now because the livestock industry in this part of the world has not had the time to adapt to it. Nor had they been provided the kind of economic support they will need to make the transition which is what Europe has done for the past few decades. But I think that there can be progress here and hopefully in some point in the future we will be able to do what EU has done and banned the use of antibiotics as growth promoters for livestock in the region.

Diagnostic Solutions

Carl: From your perspective, how important are diagnostic solutions to the control of antimicrobial resistance?

HLY: I think that they have become increasingly important and perhaps more critically both the community as well as the healthcare professionals believe that is the case and it is largely driven by this COVID-19 pandemic for example.

Diagnostic Strategies

Carl: From your comment about community and healthcare setting, what do you perceive to be the most impactful strategies for diagnostic solutions from the community to tertiary care?

HLY: I think that encompasses a wide spectrum of diagnostics. In the hospitals for instance, what we want are more precise and sensitive diagnostic tests including those that provide some idea of what the bacteria are resistant to very quickly. In the community setting, what we are trying to achieve is to help both the patients as well as the doctors quickly find out, whether the patient has a bacterial or a viral infection. So, if we have a cheap test that rapidly distinguishes between bacterial and viral infections, that would be fantastic.

Research and Development

Carl: Are there any important lessons that we could learn from this pandemic, that we can leverage quickly to get back into the fight against AMR?

HLY: That is a very good question. I would like to say yes but I am not sure whether that is idealistic or close to realistic. I think COVID-19 saw remarkable collaborations between scientists and governments, between the public and private sector. As everyone scrambled to find different solutions for the different challenges posed by the pandemic. It has shown us that you can develop diagnostic tests very rapidly, you can develop new therapeutic agents and test them in a very structured and rigorous way, very rapidly as well. And I have never seen so many vaccines being developed for any other disease in the past. In fact, probably there are more candidates for vaccines for COVID-19 than there has been for all the different infectious diseases put together. So that certainly shows us what can be done if we are aware of a threat and we collaborate together as far as possible in order to deal with it. Unfortunately, AMR has been with us for decades and it has not driven this kind of sense of urgency or the need to do something about it. So, I am not sure that the lessons that we have learnt from COVID-19 can really be translated so easily into tackling AMR. I think perhaps the closer analogy would be climate change. Climate change has also been something that has been insidiously happening for decades as well but only recently has there been increased attention and increased efforts put up to deal with this problem.

Healthcare Industry Challenges

Carl: Dr Li Yang, the pharmaceutical industry are widely acknowledged for their involvement in the perpetual arms race against bacteria to develop better weapon, but for the diagnostic industry such as ours, we also spend a lot on developing innovative technologies to support the battle. However, we find the adoption rate to be far more challenging. How can we improve this for the future?

HLY: I think rightly or wrongly, there are several challenges. I find that in hospitals, particularly the public hospitals of the lower and middle income countries. The laboratories tend to be less well-resourced and have technologists that are less well-trained, than those in high income countries to bigger hospitals. And that means that they have fewer resources to buy new diagnostic test and the patients themselves are unable to afford some of these new tests, on top of all the other hospitilisation costs. I think that both the healthcare providers as well as patients and the general public need to be educated about the value of a good diagnostic test and why they should go for it or why the healthcare provider should order it. I think that the value proposition needs to be very clear and that is something that the diagnostic company can do more. In the community setting, the challenge has always been a test that is rapid and cheap there is no escaping from these 2 parameters and perhaps that’s why diagnostic companies have not been particularly willing to invest in this regard for antibiotic resistance because the alternative of just prescribing antibiotics to the patient is far cheaper in the healthcare providers minds as well. But hopefully COVID-19 will have changed the perception of both healthcare providers and the general public such that they will see the value of such tests to distinguish between bacterial and viral infections and the diagnostic companies will be then willing to invest in developing cheap and rapid diagnostics for this purpose.

Actions to stop AMR

Carl: So, Dr Li Yang, in summary what do you think are the most important action points for the region to stop or reduce AMR?

HLY: That is a very difficult question. I have a wish list but trying to achieve them will require a lot of effort. Let’s start with the livestock industry because in some ways, it is the simplest at this point, in terms of concept. If we were able to reduce or remove the use of antibiotics as growth promoters, that is a big win already. For human health and healthcare, in the hospital setting, it is important, that we continue to educate the doctors and other healthcare professionals and improve on stewardship, for better use of antibiotics. I think what has been happening so far has been great progress, but more can be done for antibiotics to be used more wisely in hospitals and healthcare institutions. In the community setting, the key is to continue to educate the public such that they become aware that viruses do not need antibiotics and the majority of upper respiratory infections are indeed caused by viruses. That will reduce the pressure on healthcare providers as well, to provide antibiotics to them if they have upper respiratory infections. It will be good if we can restrict access of antibiotics to general public. But as I mentioned, this has to be something that should be done carefully. In rural parts if the world, access to healthcare is challenging and they should not be denied the use of life-saving antibiotics when that is needed. I think in all these areas, there is a role for better diagnostics, such as the ones that your company comes up with. Particularly in the community setting, should there be a cheap, rapid test that distinguishes between bacterial and viral infections, that will be great. We cannot escape the issue of having to develop new antibiotics. It is key that pharmaceutical companies continue to make new antibiotics and different ways of incentivizing them is necessary. Because we always have to keep ahead of the evolutionary game and have new antibiotics for use when bacteria become resistant to the old ones.