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6 Aug, 2021 06:31

Antibiotic resistance to make pneumonia and appendicitis deadly again – microbiologist

We are hardly even done with the Covid-19 pandemic, but scientists are warning that something far worse is round the corner. We talk about this with Professor Peter Collignon, an Infectious Diseases Physician and Clinical Microbiologist, and a World Health Organization expert on antibiotic resistance.

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Sophie Shevardnadze: Professor Peter Collignon, an infectious diseases physician and clinical microbiologist, expert to the World Health Organization on antibiotic resistance. Great to have you on our show today. Welcome.

Peter Collignon: Thank you for having me.

SS: Alright. So tell us, what is in brief happening with antibiotics? Are they not working anymore? Why?

PC: Well, antibiotics are still working, but less so than before because of superbugs and antibiotic resistance. And what that means is if we have a really important infection, and we treat it more and more, the antibiotics don't work. So we have increasing deaths, and increasing what we call morbidity or suffering. So people are in hospital for longer and have more complications. So superbugs and the spread of those antibiotic-resistant bacteria and the genetic material that's responsible for that resistance is a real problem because it means more and more people can't be treated properly and there's more and more deaths and suffering as a result.

SS: So if I understand correctly, at some point, if we don't do anything or, more correctly, if we don't come up with anything, healthcare will be kind of thrown back decades. And we'll have what? Typhus? What exactly are we staring at here?

PC: Well, if you look at the time before we had antibiotics, the 1920s, for instance, if you look at data from numerous countries, if you had a serious infection in your blood, like the pneumonia germ, there was about a 70 or 80% mortality within 30 days, so high death rates. But antibiotics came along with penicillin, for instance, and that death rate went down to about 10%. Same with golden staph, very common infection in people's blood, without antibiotics – 80% mortality, with antibiotics – much, much lower, maybe 15%. And E. coli, a very common germ, that's a commonest cause of urinary tract infections and bloodstream infections. Again, if you've got antibiotics, you know, most, 90% of people survive. But if you don't have antibiotics, then a lot of those people die and a lot of people even if they get better are sick for weeks or months, rather than get better very quickly. So antibiotic resistance is a real problem because we can go back to what they call the pre-antibiotic era. We’ve effectively become post-antibiotic. And in a lot of countries, particularly countries like India, China, developing countries, or low-income countries that have particularly poor water supply, the resistance levels there are astronomical. You know, half the colon bacteria like E. coli are for practical purposes untreatable. Now, if you just have a urinary tract infection, you probably get better most of the time by yourself, but if you've got a serious infection, a bone infection, a bloodstream infection, then you have a lot of deaths that were otherwise preventable when we had antibiotics that worked.

SS: Antibiotic efficiency is declining because of antibiotic overuse. Why this is even a problem?

PC: Well, it's a problem because antibiotics are such wonderful drugs. I'm an infectious diseases physician, I treat people who are very sick. And one of the joys of my profession is you have people seriously ill, you give them a drug called an antibiotic, and they get better very quickly, often, you know, five days, seven days. That's very different to a lot of other things in medicine where you have to stay on drugs. So antibiotics are terrific drugs. The trouble is they’re so good and they’re now so inexpensive we overuse them. People have, for instance, a throat infection due to a virus, and we often give them antibiotics, or a bit of a cough, where the antibiotics don't make any difference. So there's a huge overuse of antibiotics in people, but also in agriculture, to fatten chickens, for instance, to make them grow faster; and all of that combines, to mean there's a lot more resistance or superbugs travelling between people to people, travelling from animals to people via food and water. So we get rising, rising levels of antibiotic resistance getting worse and worse. And a lot of that is to do with overuse of antibiotics, particularly in people, in hospitals, in the community, but also in the agricultural sector. And then what's very important is how those germs spread from person to person or from water to people or from animals to water and then to people. This spread of resistant bacteria is making it much worse, and the worse your resources in a country, such as a poor water supply, sanitation, the worse the spread is, so the more superbugs you have.

SS: So how exactly are antibiotic-resistant bugs spreading? I mean, has this process accelerated? What are the observations of the past years?

PC: Well, I think it is accelerating. Now, different germs spread different way. For instance, the pneumonia germ, what we call pneumococcus is mainly spread from person to person by being close to them – coughing, sneezing, that goes from one person, sitting in their throat, and if they're unlucky enough to develop pneumonia with it, they get very sick. The same for the golden staph or staph aureus germ, it's in people who are close together, skin to skin contact or touching benches, you know, often that spread that way. But other germs such as E. coli, which is the commonest bacteria causing urinary tract infections, particularly in women, but also as a commonest germ causing bloodstream infections, or what we call septicemia, that's spread by numerous other ways. It can be directly person to person, but more often, it's via what we call fecal material, you know, your feces when you go to the toilet, that can be directly spread to people, but also through contaminated water. People then intake the water and they come into their mouth, the germ sits in their bowel. And most of the time, it may not matter, but if they get an infected gallbladder or a urinary tract infection, then it can matter. And also via foods. If certain superbugs develop in food animals, then when you process the animal, it gets onto the meat. Then if you ingest that meat raw, or if it cross-contaminates your lettuce or tomatoes in your kitchen, then you get it into your mouth, and the superbugs can stay there. The reason we know that's a problem, and you get a lot through the mouth, is we did a study in Australia, where we looked at a whole lot of doctors and medical students and nurses before they went on a holiday to Asia and numerous other places. They carried very little superbugs. But when they came back, half of them were carrying E. coli resistant superbugs that they picked up just from food, water, interacting with people. Seawater, for instance, can have bugs in it, including golden staph on occasion. Freshwater can have numerous bugs. And you can see in some situations, for instance, in Asia, with aquaculture, you have fishing ponds, where they actually put in animal and human feces sometimes, also antibiotics; and then when those fish are taken out, they're coated with these superbugs that can then spread not only in the local environment, it can spread globally. You know you can have superbugs you've picked up in China or the Philippines that are imported into other countries and then get spread. And if we look at what happened in England and around the world, including Australia, many years ago, there was a particular germ or resistance called the New Delhi metallo-beta-lactamase. It was named so because it was first found in India, but that was resistant to most antibiotics we've got, and people from India who travelled there brought it back to England and it caused them cross-infections or infections in hospitals in England. But the same germ came to Australia, we had a case of somebody who had gone to India for elective plastic surgery that went wrong and they ended up in an intensive care unit, came back to Australia and they needed to go to the hospital or their nursing home, they had a germ on them that they picked up in India (presumably in the hospital, but can be in the environment), that was resistant to every antibiotic we had, in their urine. So these germs do get onto aeroplanes, 747s, and travel all around the world with people who then can spread it in their new environment or where they live or where their home is.

SS: The way I see it, this is a multi-layered problem because I thought antibiotics were needed by humans to treat infections. But now we're talking about antibiotic overuse in farming, right? Can the food industry lay off using antibiotics with their animals and, you know, still be able to sustain the level of food production that we need?

PC: Well, my belief is they can. You know, I've been involved in this for 20 or 30 years. And the argument is, ‘Oh, look, we can't grow chickens without antibiotics.’ Well, that's not true. Antibiotics do make animals grow a little bit faster but mainly if they're grown in relatively poor conditions. If you grow them in good conditions, good housing, good feed, antibiotics don't make that much difference. It's only when the housing conditions are poor that it makes a bit of difference. But again, studies in Australia, but particularly large studies in Europe, and in the US, the ones I've seen, they show that when you withdraw antibiotics, you can still produce chickens at the same rate, the same weight, in same period of time, you have to do a bit of modification to how you grow them, but you can do it because there's lots of places now that can grow chickens in particular without any antibiotics that we use in people used all for the entire growth period. So while it can be a bit more difficult, it can be done. Cattle, for instance, if you put them in open pasture cattle, which is what we mainly grow in Australia, they don't need antibiotics, they take longer to get bigger because they're eating grass. If you put them in feedlots, you can need antibiotics: because of the feed they get they sometimes get infections in their liver. But instead of growing them for 100 days, if you can grow them for 103 days, in other words, grow them slightly slower, you can do it without antibiotics. So yes, it can look more difficult at times to not use antibiotics. But you can get the same result if you change your practices, and basically look after animal welfare a bit better. My own view is if you have to use a lot of antibiotics to grow animals, there's a problem with animal welfare, their housing conditions are not as they should be, their diet is not as good as they should be. Because if you do it properly, you use a lot less antibiotics. And another example is in Norway where they were using a particular group of antibiotics called quinolones for their salmon. But what they did instead, they produced vaccines. and by giving the vaccines to the salmon, they managed to drop the antibiotic usage by about 99% and got the same result. So you can achieve good food production, healthy food without using antibiotics or using a lot less if you modify your practices and use other ways to prevent disease.

SS: In general, do humans use more antibiotics or farm animals? I mean, who needs to clamp down on usage first

PC: Well, the biggest volume of antibiotics in the world is using farm animals – about 80% by volume of all the antibiotics used in the world are used in chickens, pigs and cows. Now, and that's just you know, what most countries find if they actually look at the amount of use. So that is where most of the antibiotics’ use is and where most of the superbugs are likely then produced because the type of antibiotics they use in animals is very similar to people. So what you do in animals, even though there's drugs that have got different names, and often medical doctors don't know what they mean, because they're different, it has the same effect in people. A good example is a drug that used to be used as what they call a growth promoter. In other words, just an antibiotic just to make chickens grow faster, called avoparcin. Now that's not used in people, but it's the same type of drug as a drug we're using in people frequently all around the world called vancomycin. And by using that drug in chickens and pigs, you produce bugs called VRE, or vancomycin-resistant Enterococcus that then could come across the people through the food chain, be in their gut and cause infections, or the resistance gene could transfer to the ones in human bowels. So what happens in one sector can transfer to another sector. And sometimes it takes a while, but it happens and there's numerous examples how it's happened. And that's why we need to be judicious with our use of antibiotics everywhere. In people need to use less, in hospitals we need to use less, use them sparingly, have better infection control, so we don't spread infection. And exactly the same in the agricultural industry, because it's also in their interest to not use too many antibiotics, because they run out of antibiotics then, when they have to treat sick animals. So it's in all our interest to decrease antibiotic use, and to stop the spread of the superbugs. Because if we stop the spread in people and in hospitals, we’ll use less antibiotics and have better results for people. Exactly the same in agriculture. So it's good for agriculture. And equally, then you get less cross-over from the agricultural sector, often via water to people and vice versa because we've controlled it better in both sectors.

SS: Then I’m thinking, humans once invented antibiotics, can't we just do it all over again and invent a super antibiotic that would help us deal with these superbugs?

PC: Well, we can, but every time we do it, the bugs are one step ahead or not far behind us and produce resistance. There's no antibiotic where there's no resistance. And the interesting thing about antibiotics, penicillin we didn't invent we found and it's produced by fungi. And so a lot of antibiotics are naturally out there in the environment, or things that are similar. So other germs have already learned to ‘I don't want to be killed by this antibiotic.’ So there's natural protection out there in the environment. And what we do when we use the antibiotics, we actually then give an advantage to the germ, the bacteria that's already got that resistance, we let it multiply in high numbers, and then it spreads around in people, in a country in a farm, and then eventually travels internationally. So most of the resistance that’s out there isn't just, you know, suddenly, as a new mutation, it often is resistance genes are out there for other purposes and then, in fact, it’s there and multiplied up so that that germ has an advantage by not being killed by the antibiotic use, it multiplies to really high numbers compared to the ones killed, and then is much more able to spread to everyone else.

SS: Phage therapy – there is the thing where we use a virus that eats certain bacteria instead of an antibiotic that just kills bacteria en masse. And that sounds like a very refreshing alternative to antibiotics. Is it far from being mainstream?

PC: Well, it is far from mainstream. I think, Russia and Ukraine – my understanding is – have done a lot of research on this in the past; and phage therapy, phages are viruses, and they particularly get into certain bacteria and kill them. And in fact, in Australia and elsewhere, about 20 years ago, the way we, for instance, what we call, typed or fingerprinted golden staph was to use phages, that, you know, a number 87 would kill certain bacteria. So we would name the bacteria. So in theory, yes, very good. And I think it is a reason to advance it. The only thing about phages, just like antibiotics, you can develop resistance to it and a phage doesn't work against every type of bacteria. It's selective, which is good. But it also means you can have the same problem with it, it works for a while and then doesn't work because the bacteria develop resistance to the phage. But phages are, I think, something we need to develop more because in some ways you can develop them more quickly and utilise them more quickly. But yet, so far, they haven't reached the same level of development as drugs, you know, chemicals have, particularly modifications of antibiotics to try undo the resistance. But it's an area where I think we need lots of work. And I think there's a lot of experience in Russia, Ukraine, as my understanding, where we, you know, other countries should be able to learn a lot from that and what's been done in the past.

SS: So phage therapy seems to be more custom-tailored to the exact harmful bacteria that I have in my body. Can there be an industrial-scale phage therapy use, like we have with antibiotics?

PC: Well, in theory, I think they could be because we know for instance that certain phages killed golden staph or different varieties of it, and E. coli and every other bacteria. So yes, I think they can. I understand one of the problems with phage therapy, it often works the first time, but then it doesn't work the second time in the same person, you have to have a different phage, for instance. So I think it's got a lot of potential. And it is an area that we need to develop because it's a different means of killing bacteria than what we're doing now and very selective. One of the advantages of antibiotics, they kill the bacteria, and most of them don’t harm, you know, our kidneys or liver. And this is the same with phage, they're very selective as to which bacteria they go into, which means our heart cells, our liver cells, lung cells are not damaged by it, but it just knocks off the bacteria which is what we want, something very selective. So yeah, basically, we need a lot more research and development done. And the more superbugs we have, the more it's important to look at other alternatives and phage therapy is one of those alternatives.

SS: So these new superbugs that we're talking about, their resistance to antibiotics, what are they exactly? Are they new diseases, old diseases, upgraded?

PC: Well, they're all diseases caused by bacteria we've known about for a long period of time. But now those bacteria don't respond to the drugs or antibiotics we use to kill them. So the problem is that all diseases, with all bacteria are no longer killed by the drugs. So that's why we've got to come up with either new drugs, new antibiotics, or phage therapy or something else that might kill them. Or sometimes antibody therapy is used. But whatever we use, we basically need to do things to stop those bacteria multiplying up and overwhelming the body and killing the host or making them very sick. And phage therapy, antibody therapy, in other words, things produced by white cells that kill bacteria, are all different ways of trying to treat these superbugs but none of them so far have been a, you know, panacea or a complete answer. The other important thing we tend to neglect, we tend to be somewhat overwhelmed, I think, in saying, ‘Oh we’ll come up with a new drug, and that'll fix the problem.’ The basic problem is infection control and prevention, we have to stop these bugs from spreading because we get more effects and save more lives by stopping the spread, which is often not very high tech - it’s basics, like good water, good sanitation, washing your hands. Often that's not done. And we instead think, ‘Oh, look, we want a magic pill to kill this,’ when we would get much more effect and much more prevention if we just stopped the bugs spreading as much in the first place.

SS: How contagious and dangerous can an antibiotic-resistant bug be? I mean, what we have right now is we're having a situation with a virus, which isn’t treated by antibiotics. And it is quite bad, but it's not ‘end of the world’ bad...

PC: Well, none of this is the end of the world. I mean, you know, people before antibiotics were found, they would die very frequently but not everybody would die. Most people who got an infection got over themselves. Our own white cells, our own antibodies do a lot to kill the bacteria. It's just that antibiotics help.  So it's really making sure you look after your body. And it's when you get burns and you breach your skin that lets bugs in. If you take, you know, put tubes down people's throats in a hospital that lets bugs get through a barrier that would normally stop them. So a lot of the basics of infection, not doing things to people that make them more susceptible to infection, if we can do that. But there's obviously times where we can't do it. So a lot of the things we have to do, I think are the basics. But on top of that, we do need to develop new drugs, new ways of combating the germ itself. Covid is a virus but you know, it'd be nice if we had antivirals that were very effective against it. But it's the same. Even in HIV, which is a virus, we have very effective drugs, but you can get resistance to it. Fungi, which are different to bacteria, cause now more and more lung infection, particularly in people with their immune system depressed. And again, we can get resistance to that. And so another example where we use antifungals widely for farming, and particularly in Holland, they found that some of those fungi cause infections in people with leukaemia that don't respond to the standard drugs. Bacteria are more of an issue because they're more prevalent, and we've got more drugs to kill them. And that's why we call them antibiotics. But the other broader term antimicrobials are covered drugs that kill viruses, kill bacteria, or anti-protozoan, or anti-parasitic drugs, but also antifungal drugs. So there's a wide gamut of what we call antimicrobial resistance because every drug we use to kill either a virus or bacteria, fungus, all of them we can get resistance [to] in the first place or develop, and then that can spread to other people and be a problem.

SS: Professor, thank you so much for this wonderful insight into the world of antibiotics. You know, I'm thinking, scientists were saying for decades that the pandemic is imminent. No one would listen and look at us now. So I really hope that the Covid pandemic will give the momentum to more action on the global health crisis front. Thanks a lot for this wonderful interview. Good luck with everything.

PC: Okay.Thank you.