It seems like the plot of a sci-fi movie – drug-resistant superbugs. But this reality is far from fiction. Infectious disease specialist Steven Gordon, MD, walks us through how the surge in antibiotic use launched us into the age of drug-resistant bacteria. He discusses foodborne outbreak, unnecessary antibiotic use, innovative research and what you can do to help control the spread.

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Uncovering the Truth About Superbugs with Dr. Steven Gordon

Podcast Transcript

Nada Youssef:   Hi, thank you for joining us. I'm your host Nada Youssef, and you're listening to Health Essentials podcast by Cleveland Clinic. Today we're broadcasting from Cleveland Clinic main campus here in Cleveland, Ohio. And we're here with Dr. Steven Gordon. So nice to have you today.

Dr. Gordon:  Well thank you Nada, it's a pleasure to be here.

Nada Youssef:   Thank you. Dr. Gordon, is he chairman of the department of infectious disease in the Cleveland Clinic Respiratory Institute and also the professor of medicine in The Lerner College of Medicine of Case Western Reserve. And today we're talking about antibiotic resistance and superbugs. And please remember this is for informational purposes only and it's not intended to replace your own physician's advice.

Nada Youssef:   So recently, CDC raised the alarm over an outpouring of drug resistant super bugs infecting three million Americans annually and killing four people every hour. Drug resistant super bugs kill 35,000 people each year according to the CDC. So let's start by talking about super bugs. What does superbugs even mean?

Dr. Gordon:  Well thanks Nada. I think I want to pull back a little bit by saying my comments are going to be somewhat biased. As an infectious disease physician, this is something that is top of mind for us all the time in terms of infections and treatment. What I want to say is that the CDC report, which we'll get to, what we care about most is patient outcomes. And my background as you said, is infectious disease. And I always kind of grew up interested in microbiology. My mentors where I went to residency, had trained at CDC and again, full disclosure, I trained at CDC as well. So I do think it's important for the public to know that this is a what we would say an emerging threat, but also an opportunity. So I don't want to scare anybody.

Having said that, if you look at the CDC reports, which was just released last month in November 2019, I think it's a great document. In terms of measured, but also pointing the importance of this globally, not just to the individual patients, to the States, but as they determined that this is a one health thing. So although they state, again the estimates, and this comes from a variety of data, that yes, people are in America dying of drug resistant microbes in this case, if you look at the WHO estimates by 2050 if trends continue, they state that by 2050 50 million people globally may die of drug resistant infections. So I think as I said, okay, the numbers are there, but as [inaudible 00:03:01] says, those are statistics, but all of us are affected I think individually and at the bedside we see that. So as a clinician, when we are looking at people with proven or suspected infections, our mind is focused on that patient on the outcomes. We like to go into an evaluation of someone with a proven or suspected infection with our armamentarium.

And if we're focusing primarily now on what the CDC report did, bacteria in fungal, our biggest armamentarium is often antibacterials or antimicrobials per se. We want to be assured that at least there's a good chance that they're going to be effective against the things that we treat and all of us get a little nervous when those options decrease. Now the other impact of resistance, meaning that the antimicrobials, the things we use to treat proven or suspected infections are no longer effective, is we tend to use more, we tend to use, which tends to lead to more expensive empiric therapies, which tends to lead to more toxicity and from the patient's point of view, also more costs, direct costs. But again, our focus, CDC focus is really on health and wellness and we'll get into that. But yes, these emerging and present threats are out there and it, we are mindful about that because it does affect how we manage our patients, inpatient and outpatient.

Nada Youssef:   Sure, sure. Great. So can you take a moment to first explain the purpose of bacteria in our body, both good and bad, how they function?

Dr. Gordon:  I think that's a great question. So, we tend to be always focused on things that affect us. Human means tend to be selfish, it's very anthropomorphic, but we live in a community. We live in a community, an ecosystem. And we have to remember that microbes existed before we were here and will exist when we're gone. The other thing to remember is even in our own bodies, we harbor probably two to three times higher DNA of microbial DNA than human DNA. And so there is this, what we'd say, this ecosystem that goes on in as everyone knows now there's a big research and development in the microbiome now. The community of organisms, which can include bacteria, fungal, but also other things in terms of viruses. Very interesting research going on to that and health and wellness.

So most of the time we're not at war in this regard. There's a symbiosis. Bacteria in our guts produce vitamins like vitamin K, necessity things, and some of these bacteria that also keep other things out. Now, occasionally they can become pathogens or be introduced, even our own, and that's where infections and disease can result in. So we like not to say it's a war on pathogen. We don't like using those metaphors, but more how do we live in harmony, so to speak, and obviously to control those things that can cause disease or spread within our communities.

Nada Youssef:   So would you say superbugs is a natural evolution of germs then?

Dr. Gordon:  So super bugs. I think when we talk about, or when the CDC is talking about super bugs, we're really talking about potential pathogens with increasing resistance. So it doesn't necessarily mean that these bugs are more virulent, such as the Ebola or things that have a high rate of a fatality. But it means from a clinical point of view, our armamentarium to effectively treat if they cause infections is limited. In some cases, very limited. And that makes us all a little anxious kind of going into, if you're going into a gunfight with nothing to battle them. But it also creates some innovation. And again, it's creating a lot of also basic research and understanding. You know, we have not been in the antimicrobial era for very long. Technically speaking, penicillin was put into the arms of civilians and that was a war effort, but in the late 40s and 50s and we've seen obviously a plethora of antimicrobials and there was a time when the surgeon general felt that maybe the era of infectious diseases was over. Me standing here with a job obviously pushes back against that.

So I think this is a dynamic situation and I think that our approach now is much different. Much more sophisticated. We have a plan in the States as well as globally of surveillance. That is to say you can't manage what you don't measure. So these are making sure if there's outbreaks of things and ongoing surveillance. This happens in terms of foodborne pathogens, other types of pathogens. Containment, obviously antimicrobial development and using those wisely or trying to use those more wisely as well as basic science research, which I think is extremely important. So I remain optimistic here in terms of this.

Having stated that if you look at the top five pathogens that they put on as urgent. Meaning we require aggressive attention. And this isn't always about that they're killing more people are affecting more people. It has to do with some criteria in terms of potential for spread, what the potential might look like in the future and also what we have in our armamentarium. And if you look at that list again, the CDC had 18 pathogens in their, what we call their hit list that was published, the five that are interesting, one is a community pathogen, Neisseria gonorrhea. So this is a sexually transmitted infection. Why it's on the list is although we have treatment, now about half of the million cases that are diagnosed in the United States are resistant to one antibiotic. And so it's kind of a little warning here that if that antibiotic is rendered no longer effective, well we may be in trouble there and that's why I think that made the list and again, sexually transmitted infections control, there are ways that we can obviously prevent those. And we'll get to that in the prevention piece.

The second is a new bug, so to speak, and actually only caused about 300 infections in the United States in 2018 and that's something called Candida auris. Now why is that on there? Well again, I think that was on there because it's a relatively new identified organisms causing infections in the States. It may have had its origin in other parts of the world. It's hard to control. It can spread easily and in a certain number of patients can cause infection. So I said this is kind of the new hit and it is resistant to a lot of our antifungals, not all of them. And so that's another interesting one that made the list.

There's another one that most people have probably heard about Clostridioides difficile, which is probably our most common healthcare associated infection in this country. It can affect both patients, inpatient and outpatient. It's a direct effect usually of antimicrobials used for other reasons. So this is the C. diff-

Nada Youssef:   C. diff.

Dr. Gordon:  Or things of this nature is that I think most people are aware of. It can be a complication of all antimicrobial treatments. So we're aware of that as well. It can also spread and it can also cause severe disease. So that's on there. And the last one in the urgent category, well the last two, have to do with resistance to a certain class of antibiotics. So these are usually bugs, the Entrobacteriaceae, an Acinetobactor, resistant to a certain class of antibiotic. The carbapenems that are usually found more the healthcare associated infections. They don't affect a huge number of of patients. But again, difficult to treat, options limited. And this is our carbapenem resistant Acinetobacter in our carbapenem resistant Entrobacteriaceae. And so those are the top five.

Nada Youssef:   So those are not most common one.

Dr. Gordon:  Not necessarily, right?

Nada Youssef:   Right.

Dr. Gordon:  I mean the criteria I have to do with, it's kind of like a, I wouldn't say a beauty contest, but it has to do with what's a potential threat, how easily they spread, so what patient population are they treating and what are our potential options for treatment?

Nada Youssef:   Is it Ebola on that list too?

Dr. Gordon:  No. Remember CDC-

Nada Youssef:   It's not.

Dr. Gordon:  It's a great question. I mean CDC's list, this list of antimicrobial resistant was limited to bacteria and fungi. But as you know, the most common infections in the community are viral. This gets to influenza, things like RSV. So those are important. In terms of this, you mentioned Ebola, there are things like SARS, there are things like obviously Zika in terms of this nature. So it's not to leave those off. No parasites, but the focus of the CDC report was really bacteria and fungal.

Nada Youssef:   Okay. So I want to go back to what antibiotics do to our body. So antibiotics, do they kill both bad and good germs in the body?

Dr. Gordon:  It's a great question. I mean so there's no such thing as a free lunch. And so when we talk about antimicrobials there are different classes that generally attack different what we say, segments of antibiotic microbes. Generally when we talk about bacteria, we talking about gram positive and gram negative, it has to do with their cell walls. And the antimicrobials we choose generally can branch to both. And so that's what we treat in terms of this.

Now, having said that, it's not a threading a magic bullet. The mechanisms of actions here can affect the cell wall. They can affect other things in terms of mechanisms of replication. Some kill the microbes, some stun them in terms of this, but it will affect other organisms in our microbiome. And most of us know that because if you, with children, if they get on antibiotics, you can see fungal infections in terms of diaper rashes. People can get a thrush in their mouths when they're on a antibiotics. That's the fungus because you're killing off a lot of the bacteria. And so it just makes sense that nature doesn't like a void. If you wipe out a certain population, something else will pop up in there.

Nada Youssef:   Something else will appear. That makes sense. So can any species of bacteria turn into a super bug?

Dr. Gordon:  Well any species of bacteria can become resistant to our antimicrobials no matter how well we use them. And this gets to what is the mechanism of resistance? So we all believe in kind of Darwinism and you can think of it as selective pressure. So our microbiology, the microbiome, they just want to continue to grow and develop in terms of this nature. There are compete with different niches and they can send their genetic material, what we would say as they grow, just through replication, but they can also acquire pieces of DNA. So these are the transmissible agents of resistance potentially. And these can be in many forms, plasmids, transposons and things of this nature. That part doesn't matter, but they can also acquire those resistance and that is how that you can get, if your pressure with an antimicrobial, if you have a colony of bacteria that actually have that resistance gene either present, either acquisition or otherwise, that will survive in that pressure and continue to grow, while the wild type we'd say would die off.

And bacteria can trade this material amongst different species. So promiscuous in that regard. And even dead bacteria can transfect other bacteria and acquire resistance. So that's kind of the backdrop there and that leads us to the whole issue with say, our penicillin class or cephalosporins. There are many ways that bacteria naturally are going to protect themselves. The cell wall itself is to keep out certain things and keep things in contact. Gram-positives have a certain structure, gram-negatives, intrinsic resistance, but you can imagine that there's other strategies that have developed. One is you can almost say like destroying the antimicrobial, which generally will bind a certain area, in effect an integral part of the bacteria such as making a cell wall.

If the cell walls can't be made or broken, the bacteria will die. So you can secrete what they say, an enzyme to destroy that antibiotic and render it useless. You can actually alter your target site so the bacteria no longer attaches to the target it was designed for. You can pump it out in terms of this nature or you can render it ineffective within the cell. Many strategies. The ones we focus on such as the enzymes that destroy the beta-lactamases is one. And when we talk about the two carbapenemases it's a different, a different enzyme that destroys that carbapenem class, which used to be our go to bug and probably was the first to be classified as what would say super bug or for resistance only.

Nada Youssef:   Wow, that's a lot of information.

Dr. Gordon:  Well maybe too much information but-

Nada Youssef:   That's a lot of information.

Dr. Gordon:  But again, no such thing as a free lunch. Right?

Nada Youssef:   Yeah, right.

Dr. Gordon:  I mean it's not a magic bullet per se. You're going to perturb your microflora in terms of this nature. There are also side effects aside from C. diff. People can get reactions, interactions and things-

Nada Youssef:   To antibiotics?

Dr. Gordon:  To antibiotic treatment. Obviously you're being treated for something, which is why we really are getting back to, we really want to know ideally what we're treating, right dose, right duration and if you don't need antimicrobials, it doesn't mean you're not feeling well, but that that's, we don't want to do any harm. That's still what we believe in.

Nada Youssef:   Okay. So I'm going to go back to treatments and all that good stuff. But I want to ask you one question, is it in our food?

Dr. Gordon:  So I think it's a great question. And this gets to, if we look at antimicrobial use in this country, most antimicrobials are not used for human consumption directly. Most antimicrobials are used in agribusiness or aquaculture. And that is as usually growth promoters. So as you know, we produce a lot of beef, chicken and pig. Pork. Okay. And in America there is a lot of antimicrobials used, not necessarily to treat infections, but as growth promoters.

And so maybe up to 80% in some of those antibiotics, obviously create resistant pathogens that can be found on the farm and the farmer and then back in the food chain. And that is now an interest in terms of management, and so interesting studies are looking. So if you look at some of our fast food now you're going to see antibiotic free. Oh, I mean, because some the ... You know, which is a great way to change things, right? If the consumers want something, usually U.S. manufacturers will meet that. So antibiotic free chicken and we don't grow our chickens now on antimicrobials. So that's one start. Now if you look at pork and beef, it's a little bit tougher targets because chickens by the time they're raised to harvest, it's about six weeks. For pigs, that might be six months and beef even longer. And so you're starting to see some movement there in terms of can we reduce the antimicrobial use, making sure they're not the same antimicrobials used for human consumption.

And it's interesting even last week, it's interesting in Copenhagen, pork producers there do not use antimicrobials. And how they get there is you've got to go back on the farm, animal husbandry, a little bit more room for their sows and their pigs in terms of this nature. In fact, they don't have to cut the tails off of their pigs because they have more room. In America apparently, if you go on the pig farms, the tails are clipped-

Nada Youssef:   Oh, I didn't even know that.

Dr. Gordon:  Because of tight quarters. So again, nonpharmacologic interventions in terms of how we produce our proteins and things, I think can also help in terms of reducing antimicrobial use for non human consumption.

Nada Youssef:   So it's feasible. We just need to go back to the roots of how we're raising these animals and breeding and all that good stuff.

Dr. Gordon:  I think and probably consumer pressure. So if consumers say, look it, I'm willing to pay a little bit more, or for this. That may be probably the biggest lever in terms of that. And once that happens, how can I say that? That's a big pressure. If you remember going back to the 80s there was an E. coli 0157 outbreak in hamburgers in a fast food restaurant. Now that's their brand. It turns out that Americans like their beef a little bit raw, but very quickly they learned that at 147 degrees that will control that. And so again, nobody wants to be associated with a foodborne outbreak in the food business, in terms of this nature. So that's the other target now is what we call biosecurity. So if you go on chicken farms now, there is much more infection control practice there than many of the hospitals. You don't walk into the coop, these are ... How could I say that? Very controlled environment. They don't want salmonella contaminating their egg layers or getting into the eggs. And they also use vaccines against the chickens to keep them, to keep that bioburden down, to keep us safer.

Nada Youssef:   That's good news. So are there certain symptoms correlated with these super bugs or does it depend on what we have?

Dr. Gordon:  So I would say no. So from a clinician point of view, we talk about syndromes, right?

Nada Youssef:   Yes.

Dr. Gordon:  I mean, so someone's coming in with a sore throat, a cough. They might come in with evidence of what we'd say, inflammation in their skin for a soft tissue infection in terms of this nature. Unfortunately they don't come in with a forehead saying, I have pneumonia due to penicillin resistance, strep pneumonia. Oh, okay. I mean, we're not there yet. I mean maybe if you've watched Star Trek when he puts that thing there, we'll get there. We're not there yet. So what we have to do on the clinical side is we usually, what we'd say is we treat empirically. We think based on a lot of factors, time of season, other things going on, your medical history, where you may have been, what medications you're on.

We think this is the most likely syndrome and especially if you're being admitted to a hospital, I want to err on the side of caution. We know that if you don't get effective antibiotics for an infection, outcomes are worse in terms of time to effective therapy. So we tend to want to, I'm not going to say over-treat, but what we say, cover broadly initially, if we don't. And then reassess, in terms of this nature, maybe we'll get an answer from the laboratory what it is, what it isn't. And that is I'd say the feedback loop in terms of how we approach patients when we don't yet have the exact microbial diagnosis. And for many of the things we treat, we don't actually know for sure. And again, patient outcomes are most important to us. We want our patients to get better.

Now contrast that to the pressure. Well, why are you using so much broad spectrum antibiotics? That's a community resource. If you using all this big guns on Mrs Shlabotnick, what's going to happen to the community in terms of this nature. So you can see the ying and the yang as a clinician treating an individual versus the community. And so where we're working in the hospitals is something called stewardship. Trying to use understanding that we have sick patients. If I know what's circulating in the community in say, Cleveland here, or that it's flu season or things of this nature, that will affect my choices. Especially if I know from my micro lab what our resistance pattern is, say at the Cleveland clinic, to help inform my empiric choices. Then we say after 72 hours or so, you have an antimicrobial timeout, reassess, what's the diagnosis? Laboratory things. Can you either, what we would say narrow your spectrum? Change your spectrum of antibiotics or maybe even stop your antibiotics? So that's on the inpatient side.

Lot of work and a lot of measurement. So we are measuring, how many antimicrobials we're using by something called days of therapy and where we're using those. Prophylaxis before surgery. Empiric therapy, meaning we don't know what that is or directed. And this is how I think you can affect change in terms of that. Now outpatient is a bigger space and that's where more antimicrobials are used. And this gets to what you said earlier, you or your child have a febrile illness. You don't necessarily know what it is in terms of this nature, but you want something or you want something for that child or the daycare won't take the kid back unless he or she's on something. So there's a lot of pressure to prescribe, but 30% of the antibiotics we use in the outpatient are not necessary.

So these are not that the patients aren't sick or feeling sick, but they are generally things that are not caused by bacteria, so won't respond to that. So whether it's viral, upper respiratory tract infections, or things of this nature or maybe things that aren't infectious. So that's a great opportunity but you can also see how we're trying to get stewardship there in making sure that the antimicrobials used are also directed toward what you think you're you're treating as opposed to using broad spectrum antibiotic microbials or not.

Nada Youssef:   So this is good what you're saying. So let's say my daughter does have some kind of bacteria infection. The doctor gives her antibiotics, after 10 days still doesn't work. What do you do after that if you're R resistant? And how do I know if she is?

Dr. Gordon:  Those are great questions.

Nada Youssef:   So many.

Dr. Gordon:  I mean, patients feel what they feel. I would say that for us though is the most important cornerstone for us on stewardship is correct diagnosis. This gets too interesting now because our laboratory techniques now are getting very good in terms of this with not to get in the weeds, but now we can have molecular diagnostics. And again, we have panels now potentially where you can not just test for a single pathogen, but an array of potential pathogens for this syndrome, whether it's a sore throat, whether it's the diarrheal, and again, all those are not going to be responsive or need antimicrobials. So if I have an answer for you that isn't going to respond to antimicrobial, I might say look it, it's just got to run its course. But that might be more acceptable than just continuing to treat the symptoms.

So I think it is important for patients to understand what am I being treated for and how are you going to define success? And is there utilization to try to find the precise diagnosis? And our diagnostics are getting better now. And I think that that is becoming an important. And point of care tests now are also, it used to be you have to wait for the lab. Now in our emergency departments, the technology is there that we can potentially have some point of care testing. So let's fast forward, flu season. If you've got a flu like illness in flu season, chances are-

Nada Youssef:   It's the flu.

Dr. Gordon:  It's flu. So you may not need a test in terms of this nature. And I think that becomes important. On the other hand, we know that physicians with patients with flu, not in flu season or not, when there's a lot of community, there are about 50% correct in making that diagnosis. So I think situation awareness is extremely important

Nada Youssef:   Yeah. It sounds like every patient is also customized almost right? Based on what bacteria they have. If you're resistant.

Dr. Gordon:  It could be. I mean in part of that is obviously what the host factors are. So are you a healthy host? Are you a patient who's undergone a recent transplant or on a immunosuppressed ... How could I say that? Agent. Have you traveled to someplace? Is there anyone else sick. So that's why we still think history is important and in kind of reviewing that. Sometimes on exam, there might be certain exanthems or things that will give someone a clue in terms of what this is or what this isn't. So we still are a big believer in physical exam in this regard and sometimes obviously you just don't know and sometimes it is just let's watch and wait in terms of here.

Nada Youssef:   Okay, so can you tell our listeners or viewers how we can help tackle antibiotic resistance? And how do you use antibiotics when they're given to you, because are you supposed to use them 10 days straight? What if you skipped, what do you do with the leftovers?

Dr. Gordon:  So hopefully they are not leftovers. Remember most of the time many patients are going to be treated for, empirically that is without a diagnosis. For the kids with the sore throat, most we would recommend getting a group based strep test, and sometimes that tests may be pending. If it's negative, you can stop. If it's positive, you can continue in terms of here. However, many things can appear to be infectious. So sinus is one example, seasonal or otherwise. Your sinuses you feel this, you want something, but oftentimes antibiotic is not what you need.

The same thing for what we'd say upper respiratory tract infections or things that are caused by viruses, not by bacteria. Same thing for the kids with ears, with fevers, all that is not necessarily what we would say bacterial or titis. So our pediatricians are probably better overall than the adult side and remember to, where a lot of our patients are getting care now, are urgent care centers. All right. I mean they're syndromic, they're not that sick. And so we're focusing also on our urgent care to review the protocols and things and to try to have that crucial conversation. Yes, I know you're feeling miserable, but actually an antimicrobial is not indicated here. And this is why.

Nada Youssef:   I think that's very good information because a lot of us parents or even as patients when you go to the doctor and you expect an antibiotic. Just like you said, well the teacher told me I can't bring my kid back until she's on some kind of medication. So that is very, very good information. So the focus sounds like it should be on keeping these germs from developing. So how do we take it all the way back? Talk about prevention.

Dr. Gordon:  Okay. So I think there are different levels as we said, you need a strategy here, and I think the different strategies are going to be on a global level, on a national level, a state level, and also on the individual level. And again, we need good metrics. We need surveillance. One thing that the CDC and WHO has done based on outbreaks and things is build capacity, right? So build your laboratory capacity, build your playbook. It's not a culture of blame, it's more of a team of teams in terms of this nature. You want educated consumers in terms of this nature of people to understand. You also want, I think to influence in terms of why are we using antimicrobials in agriculture. Is there a different way that's a win-win? Not shutting the businesses down but moving and saying, yes we will pay a little bit more for not having antibiotics and our raising shrimp or for our cattle or things of this nature. It's the right potentially right thing to do.

At a local level though I go back. So what are the things we want to focus on health and wellness and prevention? As an infectious disease clinician, I'd rather prevent an illness than treat it. Okay. I mean I would, in terms of this nature. Put me out of a job, I'm fine with that. On the other hand, so what can you do? So one is obviously for health and wellness, we talk about prevention of all things. Wear your seatbelts. Don't smoke if you can, or try to quit smoking in terms of this thing. Things in moderation gets your 10,000 steps in, in terms of this nature. Meditate, I mean, so in terms of this. So I think those are basic things. Other is periodic checkups. Make sure that you don't have anything going on such as high blood pressure or things of this nature. So make sure that you have a clinician and that, you're aware of that.

In terms of what you can do, obviously whether you're in the home or whether you're in the hospital, look it, when you're in a hospital, yeah, you want to make sure the healthcare workers are washing their hands. But when you're at a restaurant you want your server to wash his or her hands as well. I mean this is basic stuff. In your own kitchen, I would ask you what infection prevention are you practicing there? Are you double dipping? Are you cutting the raw meat with a knife and then cutting the vegetable? Are you keeping cold things cold, hot things hot, right? So look at your own kitchen and your practices in terms of this nature, because once things get how we say we're defrosted and things, you can still get cross contamination occurring there.

Other things we've talked about. If you take your kids to the petting zoos or things of this nature. Again, hand hygiene, right? Before and after. Animals, I love animals. I'm not going to say don't sleep with your pets or things of this nature. Although there was just a recent, I think report in the CDC about Campylobacter associated with puppies, bought in things of you know ... Puppies in terms of pet stores. So I'm pro a pet. And then vaccinations. So I think this is crucial. There's how could I say that? I'm old enough that when I was a medical student in New York Hospital and rotate on an impedes, many of the children that survived the meningitis were very much impaired and most of that was due to Haemophilus influenza. You asked the people, now the trainees, they've never seen a case. In fact, the developer of that vaccine just died this week, Dr. Robbins. And he was the first to develop an effective conjugate vaccine that was effective for two month olds, which is a very vulnerable population.

That effect itself, whether it used to be maybe a half million deaths a year from this and now in the United States it's one in a million is huge. Same thing with our other vaccine preventables. And so this is where I think we're moving and when people forget about that or our instance, our issues about measles, that can be very, very, how could I say, impacted adversely. And so I think I'm pro-vaccine in terms of this nature. We now have anticancer vaccines. Hepatitis B can be viewed as an anticancer vaccine. Human papillomavirus, HPV vaccine is really an anticancer vaccine and we have within our wearable to eliminate that through vaccination. And finally the most common that we see is influenza in terms of this. And so the flu vaccine doesn't cause a flu, but it certainly can mitigate or decrease that. So these are the types of things that we want to get out there is that there is no better product in terms of this nature. That's still the best thing one can do for influenza and many of these other things that used to cause or can cause so much morbidity and mortality.

Nada Youssef:   Good. Good information. So I want to talk about new research. Are we working on any new research creating new or more effective antibiotics?

Dr. Gordon:  So it's a great question. I think one thing that, don't waste a crisis. It creates innovation in, I think American and the world is very innovative and this gets to the importance of basic research. Thinking out of the box a little bit in other things and we're seeing that. So yes, there are new antimicrobials being developed. I think there is as of June 19 in 2019 maybe 44 at least, antimicrobials under investigation in either phase one or phase three. So things are coming. But there are also other different strategies in terms of looking at combinations of antimicrobials. There's one that is in study, I call it the iron man. So I think it's called, [inaudible 00:33:42], but it actually takes advantage of iron transport for some of these resistant gram-negatives to get the antimicrobial within the cell. Kind of a Trojan horse approach.

So a lot of innovation going on on antimicrobials in novel classes. So new classes in terms of this. There are other strategies though. So interesting. So many people may have heard about fecal transplants for C diff. So these are the live biologics, interesting things going on there. And again the microbiome, not just for altering for C diff. infections but looking potentially for other disease states. A lot of activity going on that. So that's kind of the lie biologic approach. You have adoptive immunity, so new antibody therapy directed at certain infections. Phage therapy, which are genetically engineered viruses that can attack certain bacteria. So I think there's a lot on the landscape that potentially is being looked at. And I think that that becomes important. So I remain optimistic here in terms of this nature that there will be new development of different strategies.

Nada Youssef:   Now, is it likely that these germs in our body will also develop resistance to these new drugs?

Dr. Gordon:  Oh, I think so. I mean, there's no such thing as ... But some of these are going to work on different mechanisms and I think one of the things that we've learned in infectious disease and treatments, so such as things such as tuberculosis or chronic infections such as hepatitis C or HIV, is there are different strategies to use more than one drug acting at a different mechanism to prevent the underlying resistance from emerging. And so that's why we see combination therapy in certain things like mycobacterium tuberculosis or hepatitis C is a combination pill in terms of this nature. And of course we know HIV, we haven't cured HIV yet, but we've been able to control it from emergence resistance, using again, effective combination therapy. Different antivirals, working at different targets to keep that, how can we say, keep the virus which can mutate and replicate, but to do it in such a way that mathematically it becomes very difficult for it to overcome that barrier that you're empowering with your antivirals.

Nada Youssef:   So I'm going to leave you one more question. So the problem seems clear and the solution is obvious to prescribe antibiotics only when absolutely needed. Now implementing this nationwide sounds like it'd be a hard task. What do you think about that? How would you-

Dr. Gordon:  You know, as you said, our goal, the goal is not necessarily to reduce ... I mean if I was to say it from a patient centered point of view, it's about patient outcomes, right? I mean, and in my practice, yes, there are probably times I'm over prescribing. If someone does the Monday morning review, the Monday morning quarterback, but that's okay, we accept some of that. I mean, I think what you want is mindful prescribing, right?

Nada Youssef:   Mindful prescribing.

Dr. Gordon:  So it's, if you're being given a prescription for anything, I think you want to ask the provider, "Okay, I know what this is. You're going to go with the side effects, but what is this for and how are we going to define success here?" Is it a number for your cholesterol? Is it time for me to feel better in terms of this? So that you understand. I think we all understand what the purpose of any medication that we're putting into our mouth or being injected for and understanding the potential complications. I think again, we're moving toward, it's a multiple team of team approach in. Our laboratory in terms of giving us a different testing for resistance, resistant genes, surveillance going on. So we get reports from our local county health departments from the state in terms of what's circulating, and then kind of just reports. So it's all about information and then acting on that information to hopefully decrease and mitigate harm for our patients.

Nada Youssef:   Great. Thank you. Thank you. This is all the time that we have today. It's been a pleasure speaking to you. There's a lot of information I need to take in, so this is very, very good, thank you so much. And thank you again to our listeners who joined us today. We hope you enjoyed this podcast. For more information, you can go to clevelandclinic.org/infectiousdisease and to listen to more of our health essential podcast from Cleveland Clinic experts, make sure you go to clevelandclinic.org/hepodcast and for more health tips, news information from Cleveland Clinic, make sure you're following us on Facebook, Twitter, and Instagram at ClevelandClinic, just one word. Thank you. I'll see you again next time.

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