Christopher Murray
Big Brains podcst

The troubling rise of antibiotic-resistant superbugs, with Christopher Murray (Ep. 90)

Global health expert warns about a potential ‘pandemic in the shadows’

Christopher Murray
Big Brains podcst

Show Notes

For nearly a decade, public health experts have been warning that bacteria are becoming resistant to antibiotics. In 2014, the World Health Organization even said the post-antibiotic era is near. Despite these warnings, the problem has only worsened: Antibiotic-resistant superbugs like MRSA are rising—and faster than expected. 

University of Washington Professor Christopher Murray co-authored a recent study in The Lancet, which found that antibiotic-resistant infections directly killed over a million people worldwide. The study also found that superbugs might have played a role in five million more deaths worldwide.  Murray explains what's causing this troubling trend—and how we can combat it.

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(Episode published April 14, 2022)



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Tape: A miracle out of mold. That same green mold which everyone has seen growing in bread, or ruining fruit and vegetables. This evil looking fungus would still be regarded as a pest. Were it not for a brilliant doctor, Professor Alexander Fleming of St. Mary’s Hospital, London. Who discovered that it produces the drug known as Penicillin.

Paul Rand: He quickly found that this substance was able to kill all sorts of bacteria, but it took more than a decade for pharmaceutical companies to act on this discovery.

Tape: Industrial monument to the miracle drug. Mass production Penicillin plant at Terre Haute, Indiana. One of many where the lifesaving medicine is now being manufactured wholesale.

Paul Rand: The arrival of Penicillin marked the beginning of modern medicine. It led to the development of all kinds of new antibiotics to treat infections and diseases. But pretty soon doctors started prescribing antibiotics more, and more and more. And we started to notice a problem.

Christopher Murray: I’d say that from the point when there was widespread antibiotic use, it became clear that some bacteria were able to develop resistance.

Paul Rand: That’s Christopher Murray, professor and chair of Health Metric Sciences at the University of Washington, where they’ve been studying a troubling trend. The miracle drug that has made modern medicine possible is working less and less.

Christopher Murray: It’s the classic evolution of warfare. There’s an antibiotic, it can kill and attack the bacteria, they evolve or mutate to become resistant, and then that antibiotic no longer works, and then we have to look for another antibiotic or a modification so that it can overcome that resistance pattern.

Paul Rand: Dr. Murray is one of the authors of a new study published in the medical journal, the Larsen, that finds that in 2019 antibiotic resistant infections directly killed more than a million people worldwide.

Christopher Murray: It’s a big problem.

Paul Rand: The study also found that antibiotic resistant infections possibly played a role in five million more deaths worldwide. That’s more than the number of people dying each year from HIV aids or malaria.

Christopher Murray: That’s right. The difference between those two numbers, and there’s quite a bit of controversy in the field as to the bigger number versus the smaller number, which one is the right number, it bounds sort of the reality that’s out there. In the smaller number we’re being very stringent in the criteria for saying that death is attributable to the resistance. In the inclusive number it’s just, you had a drug resistive infection.

Paul Rand: And while the world has been preoccupied with the COVID 19 pandemic, researchers warn that antibacterial resistance is another pandemic in the shadows.

Christopher Murray: It is a ubiquitous problem, and one that you should want the government and society to do something about it.

Paul Rand: From the University of Chicago Podcast Network, this is Big Brains. A podcast about the pioneering research and pivotal breakthroughs that are reshaping our world. On this episode, the rise of antibiotic resistant infections. I’m your host, Paul Rand. There’s a term you’re going to hear a lot about in this episode, AMR, it stands for an Antimicrobial Resistance. Basically, it’s what happens when bacteria becomes resistant to antibiotics, and when antibiotics don’t work anymore, a relatively minor infection can be incurable or even deadly. It’s a problem that scientists have kept an eye on for decades. But when Dr. Murray saw the numbers from their most recent study, they were shocked.

Christopher Murray: Yes. Even for the people in the field. I think it’s a surprise of how big it is. And part of the reason that they’re surprised by how big the numbers are is that there was a very influential study called the O’Neal report for the UK government on the risks of AMR. And they had started off with some numbers for 2015, they were quite a bit smaller, only 750,000 deaths, and they were the more inclusive definition. So, our five million number is the one that’s comparable to their 750,000 number.

Tape: That’s a big job.

Christopher Murray: So it’s a big job, but we do strongly suspect that in aggregate deaths due to resistance are going up.

Paul Rand: So, how are bacteria developing resistance?

Christopher Murray: Basically what they do is through chance, there are mutations in their genome that change the target for the antibiotic, the pathway that the antibiotic is attacking. They change the target and the target is no longer affected by the antibiotic. By Mutation of the DNA in the case of bacteria you “acquire resistance”. And there’s actually ways that bacteria can rapidly share these resistance genes. And so you can actually see a mechanism to resistant an antibiotic being exchanged between different pathogens. And so, resistance can spread quickly, even jumping across a species lines.

Paul Rand: Think of this like the COVID 19 pandemic. New variance emerge.

Christopher Murray: What we think of in evolutionary terms of selective pressure. It’s a funny term, but basically all it means is that you create an environment where if that mutation shows up, it’s going to succeed and it’s going to spread. Just like on COVID right now, when Omicron replaced Delta it’s because Omicron had a mutation that was made it more transmissible

Paul Rand: There is another name for antibiotic resistant bacteria that you may also have heard of Super bugs. And some of them you might already be familiar with.

Christopher Murray: So, there’s a number of these sort of “Super bugs”, and then there’s a bunch where you haven’t heard of them. Most people or some will have heard of something called MRSA, which is Methicillin-resistant Staph aureus, Staph aureus is a bug that you will see people with pneumonia quite a bit, particularly people get this infection in hospitals. And it’s one of the more common sources of drug resistance deaths in the world. TB classic, but then there are these things like something called Acinetobacter baumannii, which most people never heard of. And then a very common bug, one of the main causes of pneumonia around the world, which is the Streptococcus, Streptococcus pneumoniae, these top six pathogens are a mixture of things that maybe the media’s picked up or the audience knows about. And then there are these sort of quite... Even for those who work in global health would be super surprised to see Acinetobacter as a major cause of death around the world.

Paul Rand: If antibiotic resistance keeps trending in the same direction, we could start to be back in a world where the simplest cut could be deadly, where illnesses many of us consider routine will become life threatening.

Christopher Murray: What’s your prospect of dying if you let’s say, have a pneumonia? Now if you take all comers to US hospitals, even the ones who get hospitalized, the case fatality rate is less than 5% for pneumonia, depends on the bug, but on average for them all. Whereas in the pre-antibiotic era, it would’ve been a much higher number. Look, antibiotics are life saving drugs, they can have or reduce your case fatality rate by 80, 90%, a good antibiotic, and so truly life saving. So people who need the antibiotics must get them, and they need to get the antibiotics at work. So antibiotics really make a huge difference. If you get to the point of having a bacterial infection, a pneumonia or a bloodstream infection as examples.

Paul Rand: And not only will fear of infection out in the world become a part of life, but it will also make surgeries and other medical procedures we rely on much riskier.

Christopher Murray: Somebody comes in from a road traffic accident and has an infection in their abdomen because they’ve had trauma, lots of places you can get bacteria. Infection control is big and for certain drug resistant pathogens like Methicillin-resistant Staph aureus, that is the most common root of transmission, it’s happening mostly in hospitals through inadequate infection control.

Paul Rand: Okay. Now you went out and looked at more than 200 countries. Is that right?

Christopher Murray: Yes. First we spread the net really broadly for data. By data we had a very broad inclusive view about what we met by data. So not just lab data, but hospital admissions data, death certificates, where sometimes the pathogen is listed, linked data which is super useful, studies for an individual pathogens that are done as part of other studies, huge array of data sources. So we spread the knot broadly, and then we looked and said, okay, how many of the pathogens can we be serious about this analysis? And we ended up with the 23, and then we ended up looking at 88 pathogen drug combinations in the 204 countries.

Paul Rand: So how did this problem become so ubiquitous? Public health experts and scientists agree that one big reason is that doctors are over-prescribing antibiotics and people are overusing them.

Christopher Murray: Most patients don’t come asking for a particular antibiotic, they usually just want advice. And if your primary care provider tells you just go home and it’ll pass, that’s when patients say no, I want something and that creates a little bit of this pressure on the physician to give them something, right? But if we go around giving antibiotics to people who have a viral infection and isn’t severe, and there’s no risk of them getting a secondary bacterial infection, then what are we doing? We are creating an environment that can encourage a drug resistant bacteria to emerge

Paul Rand: And over prescription isn’t just a problem in high income countries. This has touched all corners of the globe.

Christopher Murray: In a number of countries, you can just walk into a pharmacy and buy these antibiotics without a prescription. And so this effectively over the counter or direct from pharmacy sales are why we see resistance in west Africa, as an example. It’s not just a high income settings, there is more antibiotic use in high income countries if take all the numbers together. To that end one of the really big surprises and one that I think is changing the way people think about AMR is that, we found that there was more deaths from AMR, for example, in low income countries than in high income countries.

Christopher Murray: That seems so counterintuitive because people say, hold on, there’s more antibiotic use in rich countries, so shouldn’t there be more selection towards resistance there? But because the number of pneumonias or bloodstream infections or whatever infection you want to look at are so much higher, fourfold higher in Africa than in high income country, you end up with more drug resistance. It’s a bigger problem in that low income setting, particularly when you’re counting in a number of infections and not just deaths. So it is a true global problem. And that means the potential for spread is really very global since resistant organisms can spread pretty quickly.

Paul Rand: But it’s not just the overabundance of antibiotics that we’re taking, that’s causing this problem. It’s also the amount of meat that we’re eating.

Christopher Murray: Yeah. I mean, this is one of the big concerns that everyone has, is that the volume of antibiotics that go into animals is very large.

Paul Rand: With the massive and ever growing demand for meat. The factory farm industry needs to get the most out of each animal.

Christopher Murray: It’s been shown that prophylactic antibiotics in animals leads to faster weight gain. And so in the livestock industry, there’s really widespread use of antibiotics.

Paul Rand: So, when you talk about it that way it’s that they’re not showing signs of illness, they’re doing it as a way to give them a way of putting on weight faster.

Christopher Murray: Basically. Yes. So, it is mass use antibiotics. It’s not like this cow got sick and I took him to the vet and he got an antibiotic, or she, it’s that they stick in the feed for all the cows. And so the question is, is there a jump from that clear pressure to encourage the spread of resistance genes in the animal world into the humans? It seems like that’s a real risk. And there are specific studies that trace that jump from animals into humans, what’s missing is just what fraction of human deaths from AMR are somehow linked back to the food supply. And those are the types of studies that we need to know, because it is a really big issue potentially, given the volume of antibiotic used in the food industry.

Paul Rand: This is a troubling and somewhat terrifying trend. But in their study, Dr. Murray and his co-authors laid out three key ways that we can tackle the Super bug crisis. Those solutions after the break.

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Paul Rand: One simple way. We could reverse the rise of antibacterial resistance is well, by just cutting back on our use of antibiotics.

Christopher Murray: This is pretty easily addressed by just reinforcing to physicians, just what are the downside risks here. Not regulating physicians, but getting and not encroaching on their right to do what they think is the right thing for their patient, but give them the information so that they can understand the risks and benefits that are involved with antibiotics. The right use at the right time is key.

Paul Rand: So piece of advice for the people who get nervous when they have a cold.

Christopher Murray: The responsible thing to do is to not ask your doctor for antibiotics, let them see if that’s appropriate therapy. And then always be asking the question, is there something convincing here that this is not just a viral infection and an antibiotic will have no effect.

Paul Rand: Another strategy is infection control.

Christopher Murray: Just having fewer people get infections, right? If you have fewer pneumonias, and you have fewer people with urinary tract infections, and fewer people with bloodstream infections, then the whole challenge of AMR just becomes smaller. And so that means using things that will reduce infection, infection control in some hospitals is high priority and gets adequate funding, but there are many that you visit or hear about where it’s very low on the priority list or barely in the effort to monitor and improve on infection control.

Christopher Murray: But it’s also going to be things like vaccination. We have a good vaccine, for example against Strep pneumo, which is one of the big causes of deaths from AMR. If everybody got vaccinated, we would substantially reduce that. For things like E. Coli or things that are transmitted through contaminated food or bad hygiene, then water and sanitation become a strategy. So, they sort of just reduce the volume of infection and there’s lots of pieces to that strategy, right? But we should be using them all. It is often easy to forget but when you see the numbers where there’s like four times more pneumonias per capita in Africa than in the United States, it’s just a reminder that if you can reduce the number of pneumonias period you’re going to be way ahead on AMR.

Paul Rand: We’ve certainly read that hospitals can be really quite the hotspots for spreading of Super bugs. And I just wonder is that going to a hospital? And I’m going in, my family members are going in, I’m worried about catching a Super bug at a hospital. What advice are you giving me then?

Christopher Murray: Practice basic infection control, which we’ve all now learned the basics of through COVID, avoiding surfaces, hand washing, if you’re visiting somebody who’s very sick wearing a mask, those strategies as a society we’ve become very familiar with will also stand you well.

Paul Rand: By now, you may be wondering, why don’t we just create new antibiotics that these bugs aren’t resistant to?

Christopher Murray: Well, that’s one of the big solutions, right? Which is, we invest more money in research and development to find novel antibiotics. And so one of the conclusions from our work and lots of people who are out there championing that we take AMR seriously, is that we need a bigger investment in R and D for antibiotics, both from the private sector as well as some of the basic research behind that from NIH and others. That’s a super important step. There’s no guarantee, of course that will always be coming up with novel classes of antibiotics, because it’s a research and discovery process, there’s not not a cookbook formula. It says, okay, we want a novel antibiotic, give me one in two years. The science has to find something either in nature or by design of molecules to sort of figure out what might be novel strategies for antibiotics.

Paul Rand: Is enough money going to this. And if not, what would it take to get the funding necessary to be at what would be the right level?

Christopher Murray: The feeling there is that there hasn’t been enough investment. If you go back to the 1960s, there was almost this sea change and there was a famous address, the era of the infectious disease was coming to an end and we were moving on to the era of noncommunicable diseases. And in that view that infection was on its way out, I think did feed into less investment in new antibiotics. We need the same sort of more general push through, both the public sector, research agencies, through advocacy, through public private partnerships and that really starts with awareness of size of problem, and is it getting worse. And then I think we can hope that both the industry and the public sector will respond with bigger investment.

Paul Rand: Just like scientists had been warning about a global pandemic for years before COVID 19, scientists have also been warning about the rise of Super bugs and the decline of effective antibiotics. In 2014, the world health organization released a report warning that the post antibiotic era is near.

Christopher Murray: Which is when there’s a real threat or a potential threat in logical argument on evidence, do you wait until the evidence is absolutely unequivocal to act or do you “follow the precautionary principle” and you act on the risk that this is a serious threat to human health? And the European governments and the EU have actually legislated that you should use the precautionary principle and that’s sort of why they tend to be more forward looking on climate change, unlikewise not surprising on here on AMR. And so, the reason little bit of, what’s the bar of evidence before we should act on something like antibiotic in the food supply.

Paul Rand: And in terms of tracking and having the infrastructure to track how these Super bugs are moving. Do you get a sense that based on your study and others that there’s turning into be a greater effort for tracking of these things and the global medical community is beginning to think we’ve got to really... Like we’ve done with, COVID be a lot closer linked on this?

Christopher Murray: There’s some promising signs, there are some exciting initiatives out there. The UK government through something called the Fleming Fund has invested quite a lot of money in trying to strengthen surveillance systems, the world health organization has put more emphasis on what’s called glass, which is their reporting system on surveillance. So there’s progress on the surveillance front, we’re hoping the focus on pathogens and on COVID and laboratory capacity may have a spillover effect so that if there is better pandemic monitoring, that’ll help us get better real time data on resistance patterns. Global surveillance is key and not just global but national surveillance so that you can help inform decision making in each country, absolutely key and there is some glimmer of hope there.

Paul Rand: If you’re getting a lot out of the important research shared on Big Brains, there’s another university of Chicago Podcast Network show you should. Check out it’s called, Not Another Politics Podcast. Not Another Politics Podcast provides a fresh perspective on the biggest political stories, not through opinions and anecdotes, but through rigorous scholarship, massive data sets and a deep knowledge of theory. If you want to understand the political science behind the political headlines, then listen to Not Another Politics Podcast.

Tape: Big Brains is a production on the University of Chicago Podcast Network. If you like what you heard, please leave us a rating and a review. The show is hosted by Paul M. Rand and produced by me, Matt Hodapp and Lea Ceasrine. Thanks for listening.

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