Episode 6 – Antibiotics: handle with care

Intro (00:10): 

Science on the menu, a podcast by the European Food Safety Authority.

James (00:21): 

Hello everyone, and welcome back to Science on the Menu, the podcast series by EFSA, the European Food Safety Authority. My name is James Ramsay, I'm the head of communications at EFSA, and today we're going to be talking about a really important public health issue, and that is antimicrobial resistance. And to talk us through this topic today, we're very happy to be joined by an expert at EFSA, scientist at EFSA, a vet who specialises in microbiology, Ernesto Liebana, a very warm welcome Ernesto, how are you today?

Ernesto (00:56): 

Hello, James. I’m very well, thank you.

James (00:58): 

What we'd like to do with you today Ernesto is for you to share with us your expertise, your understanding, the work you're doing on antimicrobial resistance. So, I've got a series of questions for you, but what I'd like to do at the start, just really to put the whole thing into perspective, is to talk a little bit about what we mean by antimicrobial resistance and maybe the best place to start there is by actually just talking about what antibiotics are. So, can you start us off with an answer to that question?

Ernesto (01:31): 

Sure, yes, with pleasure. So, the first thing to say is that when we talk about antimicrobials, we're not only covering antibiotics, which are, I think, the substances we will talk about today. So, antimicrobials in general are substances we use to treat infectious diseases. Let it be viral diseases, bacterial diseases, or parasitic diseases. But what is the most concerning public health issue right now is the problem of resistance to the medicines we use to treat bacterial infections, so those are the ones we call antibiotics. And what are they? Basically, as I said, they are medicines that we administer to people or animals to combat infectious diseases and they kill bacteria in the vast majority or some of them inhibit the possibility for the bacteria to grow. Most of them are found in nature, so they are produced by other microorganisms, but also most recently or recently in the last kind of 20, 30 years, some synthetic molecules have also been developed. So, this is basically what we call an antimicrobial. And just to put things in perspective, it is something that we have been living with for a very short time in history because they were only discovered about 90-95 years ago. It was when Fleming discovered penicillin back in 1928. It took a while from the discovery to their use in humans, it took almost 20 years before we learned how to purify and produce enough quantities to treat people with. And then after starting treating the first patient, which happened in 1941, it only took five years before we started seeing problems with these drugs. So, it was kind of a miracle molecule. It was helping a lot of people in need, especially during the Second World War. And then Fleming, when he gave his speech in 1945, the Nobel Prize speech, he was already warning at the time that we had to be careful in using that.

James (03:35): 

Even after just five years.

Ernesto (03:37): 

Even after five years, which is really telling us how important it is to be prudent about this wonderful resource that we have.

James (03:47): 

And I mean, so that challenge, I guess it's with us still today. I mean, that's why we're here talking about it. Presumably in that period, the level of resistance somehow is increased, or we see more antimicrobial resistance.

Ernesto (04:02): 

Presumably that is the case. So basically, what happens is that bacteria find ways of coping with this threat for them, which is an antimicrobial. And how do they do that? Well, they have different strategies. I'm talking like if bacteria could think they cannot, but in a way they are clever. So, they could, for example, produce certain proteins which have the ability to eat the antibiotic to destroy it, and these are kind of enzymes that destroy the antibiotic. They can also develop some kind of a pump mechanism. So, when the antibiotic gets into the cell, they immediately pump it out. So, they don't get affected. They may have certain characteristics on their membrane and bacteria have a kind of a wall around them. And this wall protects them from anything entering, and in this case, the antibiotic entering the cell. Or they may find alternative ways of using certain substrates for production of energy. They are living beings, so they need to eat something. And with all these mechanisms, they become resistant. And what this means is that they are able to either survive or even multiply in the presence of these antibiotics.

James (05:21): 

Yeah, wow, I mean bacteria, they know what they're doing to evade these antibiotics. And I guess over time they, you know, they develop these strategies in different ways.

Ernesto (05:33): 

Exactly. This has existed forever, it's not something that started in the last hundred years. As I said, the problem is when we increase the use of these substances, there is out there what we call a selective pressure. So, if by tons, one of these resistance mechanisms emerge and there is an antibiotic in the immediate vicinity of those bacteria, they have a selective advantage. They can grow, the resistant ones can grow, while the ones that we call sensitive will die with the antibiotic and then they multiply. And again, they are kind of clever beings in a way because they can find ways of exchanging genetic material. And that is how antibiotic resistance spreads.

James (06:19): 

Okay. I think the majority of listeners will be familiar with, you know, the idea, the need to use antibiotics prudently in a public health care setting, let's say, you know, we hear about superbugs in hospitals. We know that there are campaigns with general practitioners to reduce or not to overprescribe antibiotics. And I think that message at least, it's fairly widely diffused. It may not be followed the advice consistently everywhere. But we also use antibiotics, don't we, in agriculture? And that may not be as obvious for some people. So, could you just explain a little bit how antibiotics are used in an agricultural setting?

Ernesto (07:07): 

Sure, they have been used and they are used nowadays with different purposes. One of them, perhaps the less genuine one is using them as what we call growth promoters. So, years ago somebody realised that by giving low levels of antibiotics to animals, there was a positive impact in the speed of growth and in what we call feed conversion, meaning that the animals with the same amount of feed were able to grow faster and that was, in economic terms, a very attractive thing for farmers, so they started using some of these molecules as growth promoters. Luckily this was discontinued in Europe in 2006 and is one of the things that Europe is really proud about. Although in other parts of the world there is still use of antibiotics as growth promoters. Then the second way they are used it’s to prevent animal diseases. Sometimes done, or it was done, as a substitute for good husbandry, so you could treat animals in the right way so that they don't need to take something to prevent they get sick again. In Europe, we are quite advanced in not using them. They are still certain occasions where it is a bit unavoidable to use them and it is for example when we have to operate on an animal, on a cat or a dog or a horse, as they do with humans. But that level of use is much lower than the one I'm talking about, when you use this in a farm, you know the animals when there is no real need. There is a third way of using them, which is what we call meta phylaxis, it is a kind of complicated word but what it means is that in a farm you may have a group of animals which are sick and that you need to treat with something, and then you have animals which are in contact with them that may become sick. So, what you can do is to treat all the animals to prevent the spread from the sick ones to the healthy ones. So, in a way there is a justification for the use of the drug, but in a strict sense you are treating healthy individuals, which is again, not ideal. So, this meta phylaxis is further restricted, so if a vet would decide to do that in a farm, we'd have to justify exactly why. And then the last more intuitive way we use antibiotics in animals is to treat when they become sick, and that is absolutely necessary because it's part of keeping their welfare, you have to still have something to treat them when they get infectious diseases, and this is what we try to protect that the resistance do not hit those animal bacteria which cause them diseases.

James (09:41): 

Yeah. So, I mean it seems like there are a couple of policy initiatives or rules in place that have already been made to prevent the overuse of antibiotics in agriculture. You mentioned the phasing out of growth, you know, use for growth promotion. What are the alternatives then? You know, if you're a farmer or if you're a vet, what are some of the alternatives to antimicrobial antibiotics in the agricultural production system?

Ernesto (10:11): 

Okay, let me kind of summarise this in three areas. As you said, there are policy options or mechanisms that have been put in place. We are not there yet with kind of the ideal situation. So, the first of the pillars that is there would be what we call reducing the need to use or the level of use of these substances. And that can be done by different measures like for example, putting industrial sectors in a situation where they would have to report the amount of antibiotics that is used and then you could compare either sectors or countries or regions, and then it would be more and more difficult for those which are high users to continue if they see that their neighbours are equally producing with less amounts. So that puts pressure on everybody, and this peer pressure helps somehow. So, this is what we call the reducing alternative. But then there is, as you mentioned, the replacing one which is trying to find other substances to perhaps substitute the antimicrobials with them and examples of that would be vaccines for example. If you could prevent an animal to get bacterial infection by administration of a vaccine, the animal would not get sick, you would not have to treat, so less antibiotics needed. They are other things that may boost the immune system of the animals, immunomodulators, so these may be medicines or drugs that you give them to have a better immunity. There may be interventions in the way we feed, we give feed to the animals, for example, introducing a certain level of acidification of the feed, meaning that the pH, the acid level is high, the pH is low, the bacteria cannot grow that much, and this may help the digestion also of the animals. So many various things, various things. And then the third kind of area would be rethinking, which is really providing all the conditions to these animals to grow and to be raised in in a way where they have a good welfare that, as I mentioned before, they have a good biosecurity so that we provide better conditions in general that would help the overall health, let's say situation of the farm. So those three things in combination I think is what provides an ideal situation to tackle this problem of resistance.

James (12:33): 

Yeah, Okay. You mentioned animal welfare there and maybe use that as a way to get back a bit to what we're doing here at EFSA. So, could you just explain our role? You know, what is it that EFSA is doing in the area of antimicrobial resistance?

Ernesto (12:47): 

Yeah, the first very important thing we do is to monitor the situation. So, the European member states, they have to have a look at what is the level of resistance in certain bacteria, in certain animal species. So, they, every year, have to get the number of samples grow from them, a number of bacteria test them for resistance to antimicrobials and then report all that data to us. So, every year we get all that data and produce a report, and this report is a joint report with our colleagues in ECDC. They do the same thing for humans, and then we put all this data together.

James (13:23): 

The ECDC, just for our listeners, is the European Centre for Disease Prevention Control.

Ernesto (13:28): 

Correct. And we do this with a focus on what we call Zoonotic bacteria. So, these are bacteria that can be transmitted from animals to humans either by food or either through the environment. So, as I said, we have this collection of data, and this allows us also to look year after year how the situation progresses. So, we calculate what we call trends, and we see if in a given Member State or overall, in Europe the situation is improving. But then we also have a very important role in doing risk assessment. So it may be, for example, that a particular resistance type emerges, and nobody knows why, and we may be asked, can you have a look at the situation? Tell us what is to know about these? How can we detect it? How can we prevent it? Then thirdly, we have a role in communicating everything we do. So, activities like the one we are doing today, we are quite active also in translating as far as possible all of these into comprehensible messages. And the last thing that we have been doing and which is also highly rewarding, is spreading the wisdom of what we learned in Europe over all these years of actions to other places where perhaps they were lagging behind or didn't have the same concern about these.

James (14:43): 

Yeah, okay. Just maybe statistic on the international aspect for a moment. So, I mean, obviously at EFSA, we're concerned mainly or looking at least mainly at the sort of EU picture, how would you characterise the kind of cooperation that happens at a global level? I mean, we know it's widely recognised as a global public health challenge. Are different jurisdictions further ahead of us? Behind us? How are we working together?

Ernesto (15:08): 

As you said, this is a global problem and unfortunately you may be very active and putting a lot of effort into your immediate geographic location but if somebody else is not doing the same around you, this can be quickly jeopardised. The access to medicines, the need for prescription or not, he use of growth promotion, all these things are very diverse and not everybody's at the same pace. So, there are international organisations that are trying at least to have global standards or advise minimum standards for monitoring or for risk assessment like Codex International, I don’t know, FAO, WHO, the OIE now called WOAH.

James (15:58): 

Okay, what's the current situation? Also thinking about the trend over recent years, I mean, are things improving generally speaking?

Ernesto (16:06): 

Okay, it's a complex question. In some areas, yes, we are improving. You cannot put everything in the same basket. If we talk about, for example, levels of general use of antimicrobials, certainly in the animal sector, we have seen a constant and a steady decrease in use, which is good news. Just the level of consumption in animals was higher than the level in humans while now the lines have crossed, and it is the other way round. We are seeing this type of trends. The good news is that when we monitor what we call resistance to highly important antibiotics, so these are molecules that we use as a last resource when we get really ill and the doctors have to think about what to use, we see that the levels of resistance to those antibiotics are still low in general, relatively low or low in Europe. Although we see also differences in different locations like North, South, East or West. So, you can still see that there is progress to be made. Unfortunately, the bad news is that to those antibiotics that are very commonly used, the levels of resistance to these common drugs are still high, in some cases even very high. That tells us that there is still a problem and there is something to be done there. And that is an important message that we should not just give up and continue. The situation did get better in the use, we are still observing important levels of resistance to some of these. This is what we call nowadays a one health approach. And I think it's clear that unless all of these is taken care of because it's all connected, we would never succeed the mechanism, so we have to be watching out really that there is not a change in that because that would be a disaster.

James (17:54): 

Yeah. Would one solution not be just to develop new antibiotics?

Ernesto (17:59): 

I think, again, there was what is called the golden era of antibiotics where a lot of new molecules were discovered, and they were put in the market. And history has told us that for every single one of those, it's a matter of years before you start seeing resistance. So, it is not a very attractive, let's say, avenue for any pharmaceutical company because they will be investing heavily to produce something that as soon as it is used in the market, first you have to promote using it as conservatively as possible. And second, you know that sooner or later your product is going to fail. So, the thinking is that yes, we have to find in this society ways to help industry in finding out new ones, but we have to really protect the ones we have as gold because it's not going to be a quick fix.

James (18:54): 

Thanks very much Ernesto. I mean, you've really given us a great overview and insight into the challenge, the public health challenge that is antimicrobial resistance. Maybe just before we close, I could ask you if you were to pass one simple message or you wanted to convey something that you think is really important on this topic, what would it be?

Ernesto (19:16): 

Okay let me think about, um, I think what would be really important is that our efforts in tackling this problem are sustained in time. We cannot expect quick results, we have to be perseverant. And because all of this is connected, it is connected to humans, it is connected to the environment, it is a complex issue that does not have a single answer. I think what is really important is that everybody contributes.

James (19:53): 

So that's all we have time for today, listeners. Thanks very much for joining us again on this podcast series Science on the Menu. If you are enjoying what you hear, please feel free to subscribe. And if you want more information about antimicrobial resistance, do check out what we have on our website. You can also find more on the website and the podcast of our sister agency, the European Centre for Disease Prevention and Control. Thank you very much again and see you next time.