IRA FLATOW: This is Science Friday. I’m Ira Flatow. You might remember headlines from a few years ago ringing alarm bells about a global antibiotic resistance crisis. The issue might not exactly be front and center while we were busy focusing on combating COVID-19, but the bacteria did not take a COVID break. These microbes kept working hard to outsmart the antibiotics designed to kill them.

There’s a number of factors driving the crisis, including antibiotic use in livestock, the general overprescription of antibiotics by physicians. In fact, about 1 in 3 antibiotic prescriptions in outpatient settings, like urgent care or emergency departments, 1 in 3, are unnecessary. And scientists can’t keep up with developing new treatments needed to compensate for antibiotics that no longer work. It’s a big game of catch-up.

In the US, there are almost 3 million antimicrobial-resistant infections every year, and more than 35,000 people die as a result. Joining me now to talk about some possible solutions to this vexing problem and answer your questions about antibiotic resistance are my guests. Let me introduce them now.

Dr. Victor Nizet. Excuse me, Dr. Victor Nizet, Professor of Pediatrics and Pharmaceutical Science and faculty leader of the collaborative to halt antibiotic-resistant microbes. That’s at UC San Diego San Diego, based in San Diego, California. And Dr. Eddie Stenehjem, Executive Vice Chair of Medicine at the University of Colorado, based in Aurora, Colorado. Welcome to Science Friday.

VICTOR NIZET: Good afternoon, Ira.

EDDIE STENEHJEM: Thank you, Ira.

VICTOR NIZET: Thank you for dedicating time.

IRA FLATOW: Nice to have you. We want to hear from our listeners. What are your biggest questions about antibiotic resistance? Have you noticed a change in prescribing habits at the doctor’s office? Have you ever suspected you’ve been given an antibiotic for a viral infection. Our number, 844-724-8255, 844-SCI-TALK, or you can tweet us @scifri.

Let me begin with you, Dr. Nizet. To start off, can you give us an overview of how antibiotic resistance occurs in the body?

VICTOR NIZET: Well, bacteria, when they’re exposed to a chemical antibiotic, can either be susceptible, meaning they’re killed, or their growth is halted, or resistant, meaning they survive the exposure. And exposing them to an antibiotic is a life or death selective pressure. And by Darwinian evolution, mutations occur in the bacterial population that can lead to a change in the bacteria so it no longer binds the antibiotic– inactivates the antibiotic– so the drug doesn’t work in the humans.

IRA FLATOW: So Dr. Nizet, how does taking repeated rounds of antibiotics fit into antibiotic resistance?

VICTOR NIZET: Well, it’s a cumulative exposure. Bacteria are very small. They’re replicating every 30 minutes. So they have a tremendous mutation capacity. Each exposure to antibiotics, especially if the bacteria are not completely eradicated, gives them an opportunity to gain strength and expand their Resistance this can spread in the communities and create significant public health problems.

IRA FLATOW: So it’s sort of a survival of the fittest among the microbes. The stronger ones stay alive while you knock off the weaker ones?

VICTOR NIZET: Exactly. I don’t think there’s a better present example of Darwinian evolution. You can do it right in front of your eyes in the laboratory.

IRA FLATOW: As I outlined in the introduction, there are several factors driving the antibiotic resistance crisis. Do we know how big a role each factor is contributing to the issues? Let me ask each one of you. Dr. Stenehjem.

EDDIE STENEHJEM: Yeah. It’s a great question. And the answer is we don’t know. There’s a lot at play in terms of what is driving resistance. It’s antibiotic use in the hospital and subsequent transmission of resistant pathogen. Its antibiotic use in the outpatient setting– all those emergency department, urgent care, primary care visits that receive antibiotics. It’s antibiotics in livestock and subsequent development of resistance in livestock. And so, it’s all of these things taken together that is really driving the crisis that we’re in.

IRA FLATOW: Dr. Nizet?

VICTOR NIZET: Yes. And I think another point is that historically we’ve relied on a single class of medicines as antibiotics– these chemicals that have a direct action on the bacteria. And I believe that we’ve become complacent and maybe not had as much innovation in the field of antibiotic medicine that is necessary to most effectively treat diseases. And maybe we can take some lessons from the advances in cancer therapy and other fields, where they’ve harness the power of the immune system, developed more targeted rather than broad spectrum therapies. And with a bigger arsenal of tools for the doctors, we might derive better patient outcomes and less selection for resistance.

IRA FLATOW: So you’re focused on creating a more holistic approach to treating infection.

VICTOR NIZET: Yeah. If you think about it, having an infection is not just that the bacteria had the potential to produce disease, but that the patient’s immune system dropped the ball that day to allow the bacteria to spread deeper in the body. And what we’re discovering is that you might think of alternatives to chemical antibiotics that kill the bacteria or poison the bacteria. Rather, you might understand the tools the bacteria is using to cause disease– we call these virulence factors– and try to disarm the bacteria. An advantage of this kind of therapy is it would be specific for the individual pathogen by targeting its specific virulence factor and not have the adverse effects on all the beneficial bacteria that make up our human microbiome. And it would also reduce the selective pressure for resistance on different bacteria in the body.

IRA FLATOW: You’ve also done some research about how antibiotics are developed in the lab in the Petri dish. Why is the standard operating procedures for developing antibiotics falling apart? Is the Petri dish not good enough, representative of how antibiotics work in the body?

VICTOR NIZET: Yeah. If you think about it, the testing that we do to determine whether an antibiotic is effective– whether the bacteria is susceptible or resistant– is done in a clinical laboratory on media that is designed to support the growth of the bacteria outside the body. It’s basically beef broth and seaweed agar. It really doesn’t resemble the conditions inside the body.

And what we found is that if you test the very same antibiotics and bacteria under conditions that are more representative of the body, that have the same salt conditions and pH that are present in body fluids, you get different results. And we may be inadvertently neglecting or discounting certain antibiotic activities– ruling them out based on the laboratory test– when they’re effective in the body. Plus this testing doesn’t have any element of the immune system.

And there’s actually many antibiotics that collaborate with or synergize– they change the bacteria to render it susceptible to the immune system. And in fact, in this arena, we can repurpose many medicines that are used for other conditions, like statins, cholesterol-lowering drugs, antiplatelet drugs, anemia drugs, and find that they change the host-pathogen interaction so to speak to the advantage of the host and have therapeutic benefit in clearing infections.

IRA FLATOW: You’re saying they change the microbiome in our–

VICTOR NIZET: That’s another great idea. Rather than damaging the microbiome, we can support the microbiome. And there’s actually probiotic treatments that have been shown to benefit– fortify the barrier. Remember, all of us is not just a single lifeform.

IRA FLATOW: Right.

VICTOR NIZET: We’re really the mayor of a large community of beneficial microbes that live on our inside our bodies. And antibiotics damage the integrity and diversity of this– have led to increased rates of obesity, and autoimmune disease, and in allergy. We should fortify that– look for therapies that don’t disturb the microbiome, targeted therapies.

IRA FLATOW: I love that description of being the mayor of a large microbioma. Dr. Stenehjem, I want to talk a bit about the overprescription issue. We have known about this for a while, haven’t we? I mean, we’ve been talking about it for decades here on this program. Why are doctors still overprescribing?

EDDIE STENEHJEM: Yeah, it is fascinating that we have been having this discussion for decades. We’ve known that the large majority– not the large majority, but a large amount of antibiotics– that are given in the outpatient setting are just inappropriate. They are either not needed. Or if they are appropriate, many times they’re given at the wrong dose or for the wrong duration– say, 10 days when five days would have been fine.

And I think we’re realizing that this is a much more complex issue than what we made it out to be. For years, it was, oh, we just need to educate our physicians, and our nurse practitioners, and physician’s assistants. They just need to do better. We’ll just do more education.

And we find that it’s much more complicated than that, in that it’s not just the sheer education. We have to deal with the newfound respect of patient satisfaction and patient pressure. We need to think about the time constraints that we’re putting on our clinicians in busy urgent cares and ED where some clinicians feel that it’s just quicker to be able to give an antibiotic and move on to that next visit. We need to be able to manage all of these things and be able to design systems where clinicians feel they can take the time and explain to the patient why an antibiotic is not required, and it’s not going to be beneficial, and in many respects and many times it can be actually harmful.

We have to be able to give them that space to do that where they’re not worried about having to get to that next patient even quicker. We need to be able to provide them tools to make sure that they’re certain of their diagnoses. And I think we saw this during the COVID pandemic– to be able to give clinicians diagnostic tools to be able to put a label to the condition that the patient have. You have COVID or you have influenza. To be able to take comfort in knowing what the patient has, instead of just saying, oh, it’s a virus, it’s going to run its course.

So I think it’s a much more complex problem. And to Dr. Nizet’s point, we need to continue to evolve in the diagnostic space, the therapeutic space, the behavioral and implementation science space to really move the needle on outpatient antibiotic prescribing. Because it really hasn’t moved, at least in the adult world, for decades.

IRA FLATOW: Well, you also found that doctors understood antibiotic overprescription to be an issue, but that it was the other doctors, not themselves. Right?

EDDIE STENEHJEM: Yeah.

IRA FLATOW: What–

EDDIE STENEHJEM: Yes.

IRA FLATOW: –happened when you provided doctors with their own prescription rates?

EDDIE STENEHJEM: Right. And so, in Intermountain Healthcare, where I worked just most recently, we were able to take and do a large initiative in our urgent care network, which is a network of 38 urgent cares. And we were able to successfully reduce respiratory antibiotic prescribing significantly, from 48% down to about 30%. And part of that was being able to provide the clinicians their antibiotic prescribing rates, and allow them to see that, and allow them to see other people’s data as well.

We did this in an incredibly transparent matter where they could see their prescribing behavior and also their peers in their clinics or across the system. And in many cases where they thought, oh, I’m just doing it better, when we were able to show them their data, and allow them to compare it to peers, and allow them to talk with peers that do it better to learn from them– how do they have these conversations with patients– we saw people move in the right direction in terms of antibiotic prescribing. And in the end, not too many people were very upset about showing their data to the rest of their colleagues because they could learn from them.

IRA FLATOW: Very interesting. This is Science Friday from WNYC Studios. We’re talking about antibiotic resistance. Let’s see if we can get a call in before the break. Let’s go to George in New Bedford, Mass. Hi, George. George are you there? Well, let me try hitting the button again. George, are you there?

GEORGE: Yes, I am.

IRA FLATOW: Hi, there. Go ahead.

GEORGE: All right. I was wondering what the status of MRSA, the flesh-eating bacteria that was around and about in hospitals, et cetera. I haven’t heard anything about in its resistance to antibiotics lately.

IRA FLATOW: Gentleman, who would like to tackle that one?

VICTOR NIZET: I can speak from a scientific point of view.

IRA FLATOW: Go ahead.

VICTOR NIZET: We certainly still have MRSA as one of the leading antibiotic-resistant challenges. The rates are a little bit down from their peak. And a frightening specter of resistance to vancomycin, one of our last line antibiotics, seems to have not fully materialized.

However, patient outcomes in treatment with serious MRSA infections have kind of stalled. We see very high mortality in deep-seated infections like bacteremia and sepsis with staph, resistant and susceptible strains, which means we need better therapies. We also need a staph vaccine, which has been a real challenge for a long period of time.

But it’s in this arena where combination therapies, rapid diagnostics that let us know we’re dealing with a methicillin-resistant MRSA strain quickly, combination drugs, therapeutic antibodies– you heard about monoclonal antibodies during COVID. A beautiful paper came out from the Victor Torres Lab at NYU, showing a multitarget antibody that neutralizes the toxins that the bacteria makes and can lead to better outcomes in staph infection. So a lot of reason for optimism. But it’s still a very prevalent, leading threat.

IRA FLATOW: Dr. Stenehjem, is there one– is MRSA the top problem now with antibiotic resistance?

EDDIE STENEHJEM: Yeah, as a practicing infectious disease physician, I can tell you M-R-S-A or “Mersa” is alive and well. It is something we treat every day in the hospital. And it certainly causes very significant morbidity and mortality in our patient population. It’s one bacteria that we have high concern for and agree that we need better therapeutics for this particular severe infection. But other bacterias, such as gram-negative bacteria– these are bacteria that predominantly live in our gut that cause urinary tract infections, contrast bloodstream infections– are really seeing an increase in drug resistance, and can cause very significant mortality rates in our patients, and are really the concern of clinicians that are treating these patients in the hospitals.

IRA FLATOW: All right, we have to take a short break. And when we come back, we’re going to continue our conversation about antibiotic resistance. If you’d like to join us, please, our number 844-724-8255, 844-SCI-TALK. What would you like to talk about?

But only if you make the call– 844-724-8255 or tweet us @scifri. Stay with us. We’ll be right back.

This is Science Friday. I’m Ira Flatow. We’re continuing our conversation about the global antimicrobial resistance crisis and its solutions, with my guests, Dr. Victor Nizet, Professor of Pediatrics and Pharmaceutical Science and faculty lead of collaborative to halt antibiotic resistant microbes. That’s at UC San Diego. And Dr. Eddie Stenehjem, Executive Vice Chair of Medicine at University of Colorado, based in Aurora, Colorado.

Our number 844-724-8255. Let’s see how many calls we can get in before we have to go. Katherine in Ithaca, New York, hi, there.

KATHERINE: Hi, there. How are you?

IRA FLATOW: Hi. Go ahead.

KATHERINE: My name is Katherine. I am a registered nurse. My specialty is end-of-life care, both hospice and palliative care. And it’s been very disturbing to us as a profession to recently have patients that we are unable to keep comfortable because of the extent to which the FDA and other organizations have throttled down on opioids.

I respect that the thought is that this will curb accidental overdoses. However, that has not borne out in reality. The heroin-fentanyl combinations out on the street seem to be– in fact are– a much more deadly combination. So I do appreciate the efforts these programs that are trying to bring awareness to prescribers about antibiotic misuse, but it surprises me that the FDA has not weighed in more heavily on the matter of overuse of antibiotics leading to antibiotic resistance.

For example, there are many broad spectrum antibiotics that can be obtained without prescription that are intended for veterinary use. I wonder if your guests have any thoughts about why the FDA is not engaging in a more robust response to the issue of overavailability of antibiotics.

IRA FLATOW: Thanks for your call. Dr. Stenehjem, can you tackle that?

EDDIE STENEHJEM: Yeah. Katherine, it’s a great question. And I would say the FDA’s in the business of approving medications for use in humans. And we have had very significant progress in curbing antibiotic misuse in the inpatient setting, in the hospital setting, because of some key regulations that have come through both CMS and the joint commission. These bodies oversee and regulate hospitals.

And what we’ve seen is a very significant increase in hospital-based antibiotic stewardship programs which allow clinicians to better utilize antibiotics. We’ve seen an increase in these programs because of the advent of CMS and joint commission regulations. So we do have some policy-based guidance on the inpatient side that has improved antibiotic prescribing.

I think to your point, though, is we don’t have any policies on the outpatient side to govern and oversee antibiotic prescribing. There’s work looking at incorporating payers into this discussion, and how can we incentivize clinicians through the payer arm to better prescribe antibiotics. And I think as we move to a more value-based care model of payment structure, antibiotic overuse is going to be very front and center. We know that as antibiotic resistance go up, so does cost of health care.

IRA FLATOW: Let me see if I can get one more call in. Lisa in Yuba City, California. Hi, Lisa.

LISA: Hello. Yes. We know that antibiotics are found in most every water system. And we know that when these antibiotics and other drugs co-mingle together, they morph into various complications. So what we don’t know is how these complications are going to affect this in the future. How significant is that?

IRA FLATOW: Yeah. Yeah. Good question.

VICTOR NIZET: I can take a crack at it.

IRA FLATOW: Go ahead. Yeah

VICTOR NIZET: Victor. So yes, this is environmental release and exposure of antibiotics. We highlighted extensive use in agriculture as one source. But also, can find it in the effluent of the factories where they’re making the antibiotics, and levels of antibiotic-resistant bacteria are present in countries like India and China, where they are developing the antibiotics.

IRA FLATOW: Don’t we flush them down the toilet ourselves when we take them?

VICTOR NIZET: Exactly. And we flush them down the toilet ourselves. So wastewater detection and its sensitivity and throughput made a big impact on our management and staying one step ahead of COVID epidemiology and the emergence of variants. This was led at our University by Rob Knight as a model that was adopted elsewhere. And I think we can take the infrastructure that we’ve developed there and focus it on the key antibiotic resistant organisms and genes to get a good barometer not just from sick patients in the hospital, but the presence of the genes in the community to guide our prescription practices and target our interventions.

IRA FLATOW: Are you hopeful for antibiotic resistance and antibiotics?

VICTOR NIZET: I think it’s been said that infectious disease is the only specialty in medicine where we can reliably count on the drugs getting less effective over time and also new diseases emerging. We don’t have a new high blood pressure disease, and we don’t expect our blood pressure medicines to lose effectiveness over time, but I do believe that, following the model that we’ve seen in other fields of medicine towards personalized medicine, towards immunotherapy, maybe the pressure of this epidemic and some creative economic tools to boost antibiotic research investment, like the CARB-X accelerator or incentivize companies post-market, like the PASTEUR Act.

IRA FLATOW: Well, I’m going to have to leave it right there because we’re running out of time. We’ve reached the end of the segment. Dr. Victor Nizet and Dr. Eddie Stenehjem, thank you both for taking time to be with us today.

VICTOR NIZET: Thank. You, Ira.

EDDIE STENEHJEM: Thanks for having us.

IRA FLATOW: I’m Ira Flatow. This is Science Friday from WNYC Studios.

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