The threat of antibiotic resistance

REDDY -I’m in conversation with Professor Ramanan Laxminarayan, who is vice president research and policy at the Public Health Foundation of India. Ramanan is a health economist by training, but in the area of public health he has become one of the world leaders in infectious diseases, especially in the area of antibiotic resistance. While many people thought that infectious diseases were only a problem of the 20th Century, in this century antibiotic resistance is now being seen as one of the foremost threats to public health. Ramanan, why is it that antibiotic resistance is being feared so much across by health professionals, policymakers, and even economists? I understand that IMF has now declared it as one of major four threats to global economy.

RAMANAN LAXMINARAYAN: So as, as you know, we’ve had antibiotics only relatively recently, since 1942. Propensity for resistance has always been known. In fact, Alexander Fleming mentioned the possibility of resistance in his Nobel Prize winning lecture. And every antibiotic that has been introduced has been followed by resistance in a space of anywhere between five and ten years. And this is because the use of antibiotics, there are like four strains that are resistant, while killing off the strains that are sensitive. Now all of the antibiotics we have now are dependent on the same 16 or 17 basic compounds from which all antibiotics are derived. And we have not had very much new drug development over the last 25 or 30 years. The huge increase in antibiotic use globally has placed enormous selection pressure for resistance to increase and as a result of this selection pressure in many parts of the world, both developing and developed countries, bacterial infections are no longer responding to antibiotics. This is a much more serious problem today than it was even ten or fifteen years ago. Many of the infections that we used to only see in hospitals are now common even in the community. And because the use of antibiotics truly global, the spread of resistance has also become truly global.

REDDY: What are the reasons for this? I mean bacteria seem to be becoming resistant fairly quickly to antibiotics. And many killer bacteria are now emerging across the world threatening large numbers of people. What are the reasons why this has become such a huge problem now?

LAXMINARAYAN: So the single most important reason for drug resistance is selection pressure which is simply the quantity of antibiotics that we use. Now rising incomes, particularly in low and middle income countries have resulted in a huge scale-up in antibiotic use in places like India, China, the BRICs countries. In fact a paper we published earlier this year showed that total antibiotic consumption in humans has gone up about 36% between 2000 and 2010. And of that increase, three-quarters is just in the BRICs countries. Now this is a good thing because it means that many people who didn’t previously have access to antibiotics now have access to antibiotics. But what is bad is that many of the antibiotics are now being used are very powerful antibiotics that are not necessarily being used by people in rural areas to save lives, these are being used in urban settings by people who can simply afford new antibiotics and have no barriers to purchasing them and therefore go out and buy them. The other trend that is worrying is the worldwide increase in demand for animal protein. This has meant that in places again like India, China, Brazil, that there’s a demand for livestock meat, chicken, pigs, and cattle you know for consumption. And to produce the amount of livestock that is necessary to meet this demand, we have to intensify production which immediately means that antibiotics have become an essential part of that production process, also leading to resistance.

REDDY: Well we have seen that antibiotic resistance is being contributed both among human strains emerging as well as in animals because of profligacy of use of antibiotics. Is it mainly a problem of the prescribing doctors, whether they are physicians or veterinarians? Is it a problem of patients being, using antibiotics irregularly and improperly? Or is it a problem of the regulatory systems which is unable to provide the right guidelines and checks and balances? Or, a combination of all of these?

LAXMINARAYAN: It is a combination of all of these. I think you mentioned that economists have increased interest in antibiotic resistance. You know drug resistance is a lot like climate change in the sense that it involves this idea that each of us, whether we’re patients or a veterinarian or a livestock owner, we don’t take into account the impact that we’re having on overall resistance when we choose to use antibiotics, in much the same way as none of us really thinks about climate change when we decide whether to drive a car or get on an airplane or go somewhere. Now this just means that we use vastly more antibiotics than are necessary or warranted. And at the end of the day no one is really responsible for worrying about the problem as sort of a residual thing. That you know no one is, is in charge of antibiotics. And it’s sort of like this global commons that belongs to everyone like the Earth’s atmosphere or climate, but no one is really responsible for. Therein lies the problem.

REDDY: From you comment it’s very clear that it’s not merely a problem of biology, but also of sociology, of political economy. Now is there that kind of an interdisciplinary learning coming in for multi-sectoral actions to provide the right kind of response to this threat?

LAXMINARAYAN: Sadly not yet. I think we still see antibiotic resistance as primarily a medical problem, driven by prescriptions. It turns out that you know a lot of people worry about you know patients in India for instance getting access to antibiotics without a prescription, just going directly to the shop and buying an antibiotic. It turns out that physicians unfortunately are not very good guardians of antibiotics in the sense that a physician doesn’t necessarily do a better job prescribing antibiotics in the studies that we’ve seen in India for instance than what a shopkeeper might actually provide. All that the physician is doing is acting as a cost barrier to the antibiotic. And therefore we do need that sort of multidisciplinary learning to figure out what drives demand for antibiotics? Why do people behave the way that they do? And in that sense we need the sea change in, in norms with respect to antibiotics, the same kind that we’ve seen with tobacco for instance. You know today it’s no longer acceptable to, to smoke in an office or in a public place but it’s completely acceptable to go demand an antibiotic from your physician whether you’re in the United States or, or in China. And we have made it a different norm with respect to tobacco. We need to change that norm with respect to antibiotics as well, to make people aware of the fact that these are powerful drugs, they have important side effects and should not just be used whenever people have a, a sniffle or a common cold.

REDDY: You convened a major global conference about three years ago. And I know that a number of ministers from several countries also attended that. Is there a global movement building up against this, including the required political will?

LAXMINARAYAN: A number of countries led by the U.K. and Sweden have convened many meetings around the world to help the World Health Organization convene a global action plan to deal with the threat of resistance. And, but this has really increased awareness in many countries. Just early in November of 2014, South Africa convened a large meeting of multiple stakeholders from all of the various sectors to promise to do something against antibiotic resistance. A similar action is underway in many other countries. So there’s never been political awareness of the kind that exists now, but we need to push on in order to really do something to solve the problem. The U.K., the U.S., all of these countries are willing to act, but that is not sufficient because even a few countries misusing antibiotics can have global consequences. DR. REDDY: What’s the role of technology and information systems? The drug resistance index or the online resistance map for instance? How can they advance our action in this area?

LAXMINARAYAN: So one of the reasons why the problem of resistance had not received the traction that it really required was because people could not visualize it, they could not see it, they could not see where resistance was, was increasing, where it was remaining flat because of antibiotic use not going up  And tools like the drug resistance index and also the resistance map have been important for that visual connection to the problem, because people don’t get to see resistance. No one that they know dies of drug resistance in the way that they can understand it. Those tools are very important. I think there is also room for other tools which involve big data and so forth to be able to extract data on antibiotic use as well as resistance to further drive home the importance of dealing with this problem.

REDDY: Across the world there’s a huge scatter of data related to the production of antibiotics, the purchase and utilization of antibiotics and the emergence of resistant patterns and so on. How can big data actually contribute to a better and quicker understanding of this problem?

LAXMINARAYAN: So a great example is the fact that we don’t really have state on drug resistance in most countries, including India for instance, just because to set up a network to do this is, is incredibly expensive. However, many patients do send their blood samples on the advice of their doctor to a lab network. And the lab network will turn back a test result which says, yes, you have a bacterial infection and yes, you may have a resistant pathogen. What we’re trying to do is connect up multiple lab networks which collect thousands of samples every day, not to inform surveillance, they do it just to serve a patient need as a provider. But by connecting up these data we’re able to create snapshots of resistance that are only a week old to be able to inform both prescribers as well as policymakers. And this is possible only because of our ability to link data sets and to make that sort of connectivity possible. It was certainly not possible ten or fifteen years ago. But now these networks of data sets are giving us information that, that is extremely valuable.

DR. REDDY: If you were to make major recommendations to global policymakers in the context of the sustainable development solutions network where we are looking at environment and health and other areas of development together and position antibiotic resistance in that framework, what would those recommendations be?

LAXMINARAYAN: I think the recommendations would be pretty straightforward in the sense that first of all, the main way to deal with antibiotic resistance is to reduce the need for antibiotics which is improved public health, improve vaccinations, improve water and sanitation. These are common goals but particularly important because when we don’t address these, we use too much antibiotics. The second is to phase out whenever possible the use of antibiotics in animals because the benefits of these are not very large but the consequences for resistance is extremely high. The third is to invest in good surveillance. It really doesn’t take a lot of money, it really takes these kind of innovative methods to connect up large data sets, to get a better understanding of the situation to do with resistance and antibiotic use within countries. The fourth is to invest in new tools. We need ne

w antibiotics but we also need other tools like better diagnostics because for instance if we had a diagnostic device that would tell us within 20 minutes whether the patient had a bacterial infection, imagine the amount of antibiotics that we could not use and still make the patient better. And fifth, we need political commitment. This is a problem that is not going away. And as far as we can see, our grandchildren and their grandchildren are still going to need antibiotics. We have not found a good substitute for antibiotics yet. And knowing that the bacteria will always fight back, this is a problem that’s going to stay with us for a very long time.

REDDY: Thank you Ramanan. Bacteria will always fight back, but humans must respond intelligently. If the production and use of antibiotics for human health and welfare has been a product of human intellect, then the growing problem of antibiotic resistance is a problem of our foolishness and how we are using them. So I think antibiotic resistance, while it’s a major public health challenge of the 21st Century is something that can be met with if we take the kind of steps that Ramanan has advised us to take. Thank you.

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