Dr. Arjun Srinivasan: We've Reached "The End of Antibiotics
Explain to me why the discovery of antibiotics was so important for medicine.
Antibiotics were one of [the most], if not the most, transformational discoveries in all of medicine. Infections are something that we struggled to treat for many, many years, for centuries before the advent of antibiotics, and infections were a major cause of death before the advent of antibiotics.
So with the discovery of this new class of drugs, we overnight had an ability to care for people and offer them not just a treatment but a cure for an illness that previously would have taken their lives in a rapid manner. ?
They really are miracle drugs, and not only have they saved the lives of millions and millions of people ? but antibiotics have opened up new frontiers in medicine that would be impossible without them.
For example, organ transplantation. One of the major causes of death in patients who would have an organ transplant would be an infection. Without antibiotics, we wouldn’t be able to treat any of those infections.
And stem cell?
Stem cell transplants, bone marrow transplantation, cancer chemotherapy would be largely impossible ? because all of these are therapies that weaken people’s immune system, which of course makes them then vulnerable to infections. We don’t have to worry about that so much because we have antibiotics that can treat those infections.
A lot of the therapies that we use now for different types of arthritis, like rheumatoid arthritis ? you see ads for that now on television ? again, these are therapies that weaken immune systems. They make people vulnerable for infections, but because we have antibiotics, that’s not something that we have to particularly worry about as much as if we didn’t have the antibiotics.
So they have really transformed the practice of medicine, perhaps unlike any other drug that’s available to us.
?How does resistance work, and why is it a problem?
Bacteria, like any living organism, want to survive. They are adapted that way, and any successful bacteria is the bacteria that’s most able to survive in the environment. So bacterial resistance is largely inevitable, because bacteria will always change in order to survive.
So anything that we do to try and kill bacteria, or anything the environment does to try and kill bacteria, bacteria will eventually discover ways or find ways around those.
It’s important to know that this is a phenomenon that plays out in nature. Most of the antibiotics that we have available to us now were derived from products in nature. So penicillin was an agent that was excreted by molds in order to kill bacteria. Eventually bacteria will evolve, and they’ll adapt ways around that to overcome that obstacle.
There are lots of bacteria. They have the advantage on us in terms of numbers. And whenever you have that many of an organism, it’s likely that one among them will be resistant to an antibiotic.
If you use an antibiotic, then that one among the group that is resistant becomes the predominant one. So resistance is something that is an inevitable consequence of bacterial evolution. But it’s also something that we have certainly helped along the way.
We’ve helped it?
We’ve helped it, absolutely, by the overuse and the misuse of antibiotics, and this is something I think that we have to own up to. We’ve fueled this fire of bacterial resistance.
These drugs are miracle drugs, these antibiotics that we have, but we haven’t taken good care of them over the 50 years that we’ve had them.
So why is it a problem?
The more you use an antibiotic, the more you expose a bacteria to an antibiotic, the greater the likelihood that resistance to that antibiotic is going to develop. So the more antibiotics we put into people, we put into the environment, we put into livestock, the more opportunities we create for these bacteria to become resistant. ?We also know that we’ve greatly overused antibiotics and in overusing these antibiotics, we have set ourselves up for the scenario that we find ourselves in now, where we’re running out of antibiotics.
We are quickly running out of therapies to treat some of these infections that previously had been eminently treatable. There are bacteria that we encounter, particularly in health-care settings, that are resistant to nearly all ? or, in some cases, all ? the antibiotics that we have available to us, and we are thus entering an era that people have talked about for a long time.
For a long time, there have been newspaper stories and covers of magazines that talked about “The end of antibiotics, question mark?” Well, now I would say you can change the title to “The end of antibiotics, period.”
We’re here. We’re in the post-antibiotic era. There are patients for whom we have no therapy, and we are literally in a position of having a patient in a bed who has an infection, something that five years ago even we could have treated, but now we can’t. ?
?I wonder if you can reflect a little bit and describe how the MRSA phenomenon, this resistant bacteria, changed public awareness about the problem.
So methicillin-resistant Staphylococcus aureus, or MRSA, for a lot of people is the first time that they had really encountered one of these highly drug-resistant bacteria. ?
Literally for decades it’s been something that’s been difficult to treat. There were, up until recently, limited treatment options for MRSA. There is really one antibiotic that was available to treat it.
Was it that bad? Did people die from it?
People did die from it. It caused very serious infections. ? MRSA was something that if you asked any doctor or nurse about MRSA, they would tell you, “Oh, yes, it’s a very serious issue. We struggle with it in our patients, in our intensive care units,” but if you asked the average person outside of hospitals about MRSA, they probably would never have heard of it. That all changed maybe about a decade or so ago.
We began seeing MRSA infections outside of health-care settings. ?
We were seeing it in young people who were athletes, who were young football players who had serious infections, who died of these MRSA infections which had previously been limited to hospitals.
We saw outbreaks in schools. We saw outbreaks in health clubs. And what most of these people were getting was something very different from what we saw in hospitals.
In hospitals, when you see MRSA infections, you oftentimes see that in patients who have a catheter in their blood, and that creates an opportunity for MRSA to get into their bloodstream. They’re on a ventilator, so they have a tube that’s in their lungs, and it creates an opportunity for MRSA to get into their lungs. ?
In the community, it was causing a very different type of infection. It was causing a lot of very, very serious and painful infections of the skin, which was completely different from what we would see in health care.
What’s very interesting is that we now know that what happened here was not that MRSA escaped from the hospital and began causing infections in the community. The MRSA in the community was a completely different type of organism, or Staph aureus, that evolved this resistance to methicillin, to these drugs that we used to treat it. ?
So when MRSA showed up in the community, was there a lesson from that?
There were a few lessons that we learned from the MRSA emerging as a community pathogen. One is the fact that despite what we knew in health care about drug resistance and antibiotic resistance, we hadn’t done a great job of educating people about how serious the problem was, because there were a lot of people for whom this was the very first time they were encountering this phenomenon. ?
The other thing we learned, of course, is that these highly drug-resistant pathogens that we had for a long time thought were really an issue limited to hospitals and health care didn’t have to stay there. And in retrospect, it makes obvious sense that bacteria don’t respect any border. They don’t respect the door of the hospital, and so it makes sense that we could encounter these types of resistant infections outside of our hospitals and health care settings. ?
? In the last decade, there have been some other developments, especially with Gram negatives. Can you describe for me a little bit about what happened there with Gram negatives and why was that important and dangerous? ?
The issue with Gram negatives that I think is really important is that the Gram-negative bacteria are a large group of bacteria that generally do a very good job of developing resistance to antibiotics. ?
What do you mean?
A lot of Gram-negative bacteria, they come out of the box, if you will, resistant to a number of important antibiotics that we might use to treat them. We’re talking about agents with names like Acinetobacter, Pseudomonas, E. coli.
These are bacteria that have historically done a very good job of very quickly developing resistance to antibiotics. They have a lot of tricks up their sleeves for developing resistance to antibiotics, so they’re a group of agents that can quickly become resistant, can pose major challenges to resistance.
And what we’ve seen over the past decade is these Gram-negative agents becoming very rapidly more and more resistant to all of the agents that we have available to treat them.
To all of the agents?
There are Gram-negative bacteria that have developed resistance to everything, for which we have no viable antibiotics left to treat them. ?
So why are we so worried about these new bacteria that are Gram negatives, and what’s happened recently?
?For a long time we’ve seen Gram negatives develop resistance to antibiotics, but we had other tricks up our sleeves. We had other antibiotics that we could use.
Increasingly, though, what we’ve seen is that they’re developing resistance even to the agents that we’ve been sort of holding back and only using in the most serious infections. They were our last, best line of defense, and we now see some of these Gram-negative organisms that are resistant to even that last line of defense.
What that means is that we’ve had to actually reach back into the archives, if you will. We’ve had to dust off the shelves [and revisit] some older antibiotics that we haven’t used in many, many years. We stopped using them because they were very toxic, and as new antibiotics came about that weren’t so toxic, we of course stopped using these older antibiotics.
Colistin is a great example. And now we’re back. We’re using a lot of colistin, and we’re using more of it every year. It’s very toxic. We don’t like to use it. It damages the kidneys. But we’re forced to use it in a lot of instances.
But what’s really worrisome is that now we’re seeing bacteria that are resistant even to colistin, so there are infections for which we have really nothing to offer a patient. We’re in a situation where the patient will get better or the patient won’t get better based on whatever the defenses the patient might have, but we have nothing to offer them to help them get better.
? What are [the bacteria] doing? Are they hiding? Are they destroying? What are the weapons that bacteria have to fight the miracle drugs?
Bacteria have a lot of weapons that they can use to fight off antibiotics. One of the most common ways that they fight off antibiotics is actually just destroying them. They develop what we call enzymes, which is a fancy word for saying something that can chew up, so we put the antibiotic in, and the bacteria produces a chemical that chews it up. It destroys the antibiotic. The antibiotic becomes ineffective.
The bacteria are surrounded by a wall. They can change that wall in different ways to even prevent the antibiotics from ever getting in in the first place.
Bacteria also have ways that they can pump the antibiotics out, so even if we can get them past the wall and get them past the chemicals that would chew them up, the bacteria then turns around and just pumps them right back out again.
And many bacteria have more than one of these weapons simultaneously.
?Gram negatives have all of these weapons at their disposal, and many of the highly resistant Gram negatives that we see have all of these weapons at once that they’re using.
?What’s concerning is that what we also see with Gram negatives is that they are able to pick up weapons from their neighbors, if you will.
I don’t understand
Resistance, some of these weapons, are carried, if you will, by genes, so the gene is what tells the bacteria how to make the weapon. Some of these genes are now carried on little pieces of DNA that are very movable between one bacteria and another.
What we’ve seen is that one particular bacteria will develop resistance. It will put that resistance gene onto a little piece of DNA, and it might put a whole bunch of different weapons onto a little piece of DNA. So now you’ve got one piece of DNA that has the code for several of these resistance weapons, these genes, and that can be moved to a different bacteria. ?
Let’s talk a little bit about the antibiotics themselves, the drugs. What’s different today from the ’60s and ’70s with the drugs?
We’ve done a lot with antibiotic development since the very first antibiotics were discovered. We have antibiotics that are very nontoxic. They’re very safe to give. They’re very, very targeted at the bacteria. ?
They kill bacteria, and they don’t do much harm to the host, to the human cells, and that’s great. It makes them drugs that are easy to use. It makes them drugs that are nontoxic to use.
We’ve over time developed antibiotics that got around a lot of the weapons that the bacteria had to become resistant, so we were really ahead of the game for a long time. We were quickly developing new antibiotics. When bacteria developed resistance, we always had a new antibiotic waiting in the wings, and we had new therapy that we had to offer.
So what happened?
It all changed several years ago. What we found is that the pace of development of new antibiotics really began to slow down about a decade ago, and now we began encountering these highly resistant infections, and we didn’t have new antibiotics to use. We had the ones that we had, but we didn’t have anything new.
Why did it begin to slow down?
?There’s probably a variety of factors that have contributed to the fact that we don’t have new antibiotics. One might be that we developed a lot of the antibiotics that were easy, if you will, to develop. ?
There are some people who say we sort of picked all the low-hanging fruit, and then it got really hard to develop new antibiotics.
Another reality is there’s not much money to be made in making new antibiotics, so we saw a lot of drug companies who left the field of antibiotic development because of this combination of factors, that it was getting really hard to discover, to develop new antibiotics, and you don’t make a lot of money in selling these drugs, so the market really wasn’t there.
?I can’t tell a patient who has a resistant infection, “If we can get you through this next six months or this next year, there’s going to be a great drug that’s coming.” Or I can’t tell oncologists, for example, “Well, six months from now we’re going to have therapies to offer you; we’re going to have something to combat these infections.”
Why? The drugs aren’t there?
The drugs aren’t there. And we know it takes a long time to get drugs from the development stage through testing and into the market. Right now, I can’t tell you when you’re going to have a new antibiotic to treat these highly resistant Gram negatives. The best I can say is it’s probably going to be several years, but I can’t point to one that’s in development and say, “We’re going to have that one in three years.” And that’s a scary place to be in.
? You say you can’t make much money. I guess our society took it for granted that antibiotics were relatively cheap compared to chronic-disease drugs, but also isn’t there some economic calculations in these companies as well? Pressures on them? I don’t think they pulled out because they just don’t care anymore, right?
?Infections are not that common compared to other types of conditions like high blood pressure or high cholesterol. It’s a reality that many of the drug companies left this market because of financial realities that are placed on them. These are companies that are for-profit companies, and like you said, they have to answer to people. They have to develop drugs that will make money, and that’s not an antibiotic.
? Can you describe to me a little bit of what went into the thinking with [Centers for Disease Control and Prevention (CDC) head] Dr. [Thomas] Frieden’s announcement in March about the “nightmare bacteria” in the publication Vital Signs?
?This new, highly resistant bacteria that we talked about in the Vital Signs is one that has really concerned us simply because it is completely resistant to the most commonly used antibiotics, including some of the last lines of defense. It’s one where we really do have to reach for older, fairly ineffective therapies. It’s one that we saw spreading rapidly within our hospitals, and not just hospitals.
So this is just one bug?
It’s a family of bugs.
Is this the Klebsiella pneumoniae?
That’s right. So Klebsiella pneumoniae is one bug in that family, but it happens to be the bug that is the most common that’s developing this very powerful resistance to our antibiotics.
So there are confluences of factors that are really, really beginning to concern us. One is that it is highly drug-resistant. We didn’t have many therapies or, in some cases, any therapy to offer these patients.
We began seeing reports from people who were doing some fairly detailed studies, looking at patients who get these infections, and they were saying, “Gosh, in our experience, if you get this resistant bacteria in your blood, half the time those patients die.” Incredibly serious infections.
We began seeing outbreaks of these infections in hospitals, suggesting that it was highly spreadable within our hospital. So that’s something that’s very concerning.
We also began seeing reports from people who were studying these bacteria in the lab, and they began telling us, look, not only are these bacteria themselves very transmissible within health-care settings, but these bacteria also have the genes for this resistance on these little pieces of DNA that are really very movable, so you also have to worry about the bacteria sharing these resistance weapons with other organisms.
There’s really this combination of all of these factors as something so concerning to us that we felt the need to really sound the alarm. It’s an alarm that we began sounding several years ago. In 2009 the CDC released recommendations for how hospitals should combat this new type of resistant bacteria, and the Vital Signs I think was a good opportunity for us to reiterate that call, make it even more urgently, if you will, that we really need to do something about this.
It’s still a relatively infrequent occurrence in most U.S. hospitals, and that was something that we emphasized in the report. It’s bacteria that has been reported to CDC from about 4 percent of our acute-care facilities in the United States. So some have said, “Why are you sounding the alarm for something that’s not present in 96 percent of the hospitals that are reporting information to you?”
And to me, that’s the answer. It’s because 96 percent of hospitals have not reported this to us that we need to act now. This is one that we can’t wait around for it to become a bigger problem before we take really aggressive action. It kills too many people. We have too few options to treat it. It spreads too fast. We can’t wait.
? Talk to me about your interaction and how did you bring this alarm to fruition and the process with Director Frieden.
Every year, CDC, our group does a Vital Signs report on an issue that’s of pressing importance to health care safety. ?
We began having discussions: Is it time to sound the alarm about this, or is it just too soon? Are we just being overly alarmist if we really call attention to this problem that’s not present in the vast majority of hospitals in the United States?
As we began discussing this in small groups and discussing it with more and more people, our thinking on it really began to get to the point of, why are we following that same paradigm that we’ve always followed, which is we’ll follow the resistance for a while, and when it gets to be a really big problem, then we’ll sound the alarm and we’ll act on it?
That hasn’t worked so well for us. We’ve really been behind the game with a lot of these highly resistant pathogens. We began talking and thinking and saying maybe it’s time for a new model. If we’ve not been successful in combating the microbial resistance so far, maybe it’s because we haven’t acted at the earliest stage, when it first came to our attention, to really try to get people to take aggressive action.
Let’s break that mold. Let’s do something different. Let’s take an aggressive stance. Let’s encourage people to take a really aggressive stance at an early opportunity here. And that’s when we decided that this was what we were going to feature. ?
With this alarm out, did you tell the secretary of health and human services you were about to do this? Did you tell the White House?
Absolutely. There’s a chain of approvals for these Vital Signs reports, and so it is put in front of a lot of different people. All of the information, how we’re going to communicate about it, is communicated up to the Department of Health and Human Services and on up.
I’m just curious, because in this same time period, the director of the WHO [World Health Organization], Dr. Margaret Chan, made a similar statement, and also the top public health official in the United Kingdom talked about a catastrophic end event of antibiotics. I wondered if you’d been in touch with them, or was it just serendipity, or was this planned that you would all warn?
It wasn’t. We hadn’t really been in direct conversations with the folks at the WHO, with the folks in England. ?
But it was really interesting to us to see that in a very short period of time, you had some of the world’s leading public health clinicians from multiple different places who really reached the same conclusion at around the same time, that this was a pressing, serious problem; it was a nightmare; it was something that requires urgent attention.
This was a very loud alarm and certainly was heard by a lot of people. What did you think of the reaction to it?
I was actually pleased with the reaction to it. One of the things we worried about was would we simply get fear as a reaction, because the goal of sounding the alarm is not to generate fear; it’s to prompt action.
What we saw in reaction to the Vital Signs report was people asking the right questions: What can I do? How do we confront this problem? How do we combat this? That’s exactly the discussion that we want to have. The reaction we want was not, “The sky is falling.” The reaction is, “Well, what can we do now so this does not become a bigger problem tomorrow?”
What’s the real scope of this problem that you’re worried about?
We worry a great deal about antibody resistance among these Gram-negative organisms. The Gram negatives are a large family. They comprise many, many different types of bacteria. But within them, there’s one group of these Gram-negative bacteria that we’re especially worried about.
It’s a family of Gram-negative bacteria that lives in our intestines, and they go by the fancy word, the Enterobacteriaceae, which comes from the root meaning “inside,” meaning they live inside of people. They live in our intestines. It’s a group of bacteria that is a very common cause of infections, both in hospitals but also in the community.
Can you describe for me your worry about this particular category of bacteria?
? It includes some very, very common types of bacteria that lots of people have probably heard about, including one called E. coli, which many of us have heard about as a cause of illness. ?
What we’ve seen over the last decade or so is that this group of bacteria is becoming more and more resistant to antibiotics, and over time, as resistance has continued to develop, we’ve had to use more and more powerful antibiotics to treat these Enterobacteriaceae infections, and that wasn’t an issue for us, because we always did have the next one.
Several years ago, we encountered a situation where we really ended up in a place where we were down to our last one. We were down to a family of antibiotics called the carbapenems, which were a very powerful group of antibiotics, and they’d always been our savior when we needed them. Whenever we encountered a resistant infection, we were inevitably able to turn to the carbapenems, and we knew that they would work. And that all changed.
?Around 2000, there was a report of an Enterobacteriaceae ? in this case it was one called Klebsiella ? and it was resistant to carbapenems. That was not something that we had ever encountered before. ?Then we began to see it in sporadic reports, and then we began to see it more and more frequently.
?There were pockets, places like New York City, where they really began seeing this type of carbapenem resistance on a fairly regular basis, and it led to the coining of this term called CRE, carbapenem-resistant Enterobacteriaceae, this group of bacteria that was really resistant to antibiotics, resistant to our last line of defense, where we were now really struggling to find effective therapies and in some cases where we had absolutely no therapies at all.
?What did you do? And what did you see?
?We began looking at our data at CDC, and we found that over the course of a decade, they had gone from being reported by about 1 percent of hospitals in the country ? they’d quadrupled in the span of a decade. They’d gone to 4 percent. Maybe a small number, but still a very concerning trend to us.
? What has been the federal response to this problem that you call nightmare bacteria?
?We’ve taken a number of steps to try and raise awareness of it, to educate people about what these bacteria are and why there’s such an urgent need for action. We’ve developed recommendations for the types of actions that we want people to take. It’s not enough to tell people they need to take action. You’ve got to arm them with some things that they can do, and we’ve done that.
So we recommend, for example, a screening protocol for patients in hospitals where they’re encountering these resistant types of bacteria. We’ve told them how they can test other patients for the bacteria, which we think is especially important right now where we don’t see this very often. We want to know who has it in our health-care facilities. We want to know if we have other cases that we don’t know about. ?
We’ve recommended that when you encounter these types of bacteria, these patients need to be placed into what we call isolation. We need to place them in private rooms whenever we can. When health-care workers enter those rooms, they need to wear a gown, and they need to wear gloves. When they leave the room, they need to take off that gown and gloves, and they need to wash their hands really carefully. So we’ve recommended ways to prevent the spread of these bacteria.
We’re also calling upon people and trying to educate people about how to improve the way that we use antibiotics in our hospitals and outside of our hospitals, because we know we have to approach resistant bacteria on two different fronts.
We have to prevent them from spreading when they develop, but we also have to take steps to stop them from developing in the first place, or at least slow down their development. And the best way to do that is to improve the way we use antibiotics.
CDC has engaged in a number of efforts to try and help clinicians improve the way we use antibiotics in all of our different health care facilities and doctors’ offices, hospitals and nursing homes.
? Talk to me about the public policy response to antimicrobial resistance. Has it been response up to the level of the alarm that you sounded?
The federal government has actually taken a fairly broad approach to antimicrobial resistance to antibiotics. ? There have been a number of different groups within the government that had to be engaged, and that have been engaged. ?
Many years ago, there was the development of something called the Interagency Task Force on Antimicrobial Resistance. There was a call to bring all of the relative groups together and to say: “We need all of you to work together. All of you have different pieces of this puzzle, and you all have to work together on them.” ?
I think the message from this group was that any one of you working alone is never going to be able to solve this problem. Only by having all of you work in a coordinated way could we really get to the bottom of this.
? The Interagency Task Force was formed in 1999. ? It meets once a year, and I just wonder, what has it accomplished?
? What the task force does is it helps ensure that there’s communication between the agencies, so not just once a year.
Obviously there are scientists at all these agencies who are communicating on a regular basis. But it provides some points of contact, so if there are issues at CDC, if there are issues that I’m worried about with respect to research, with respect to drug development, I now have a point of contact at the NIH [National Institutes of Health], at the FDA [Food and Drug Administration]. ?
There’s a framework. There are people who now talk on a regular basis. There’s a formal meeting once a year where there’s a formal plan that’s developed. But I think even more important than a formal plan are the parts of work that have come about that I think have progressed because there is now a coordinated strategy to combat resistance.
You know, for something as important as resistance, which you’ve described so clearly ? how it’s changing, how it’s gaining ? I’m tempted to ask, you know, if this is a really big public health problem, who’s in charge of this problem for the United States government? Can you tell me who’s in charge?
Who’s in charge of resistance?
Of anti-microbial resistance and fighting it. It’s a threat to public health, right?
It is a threat.
So who’s in charge of dealing with that? Of coordinating it?
Well, I think the issue of who’s in charge of combating anti-microbial resistance speaks to the fact that this is a very, very complex problem, so you can’t really have one solution to the problem. If there were one solution to the problem of anti-microbial resistance, I think you could have one group that was in charge.
Dr. Srinivasan, I’m just thinking back a little bit about history that when we do have big challenges in public health, oftentimes we’ve tackled them in a big way. I’m thinking about, for example, HIV/AIDS and how we tackled that problem, and it required a lot of effort and people were in charge. And I took a look the other day at the research levels devoted to the problem of anti-microbial resistance at NIH. Anti-microbial resistance is way down the list.
It’s actually number 70 on their list. What does that say about the priority?
Well, what I think that points to is the fact that our research in this area has lagged. ?We’re going to have to do a lot more in the area of antimicrobial resistance. You know, I think for a long time, we weren’t investing a lot in anti-microbial resistance because we always had new antibiotics to combat the problem.
We got complacent.
In a sense, I think we did. You know, there were always new drugs to treat these infections and so I think the need to do basic research on anti-microbial resistance moved down our priority list.
And do you think that this is also a problem in which society hasn’t really made it a high enough priority? I know that in some diseases, there are very outspoken groups of advocates and patients, victims. Is this somehow different?
I think you’re right in that there isn’t a loud voice out there calling for more action on antimicrobial resistance, and I think that’s unfortunate, because the most powerful voice in any discussion of health is the voice of the patient. And here we don’t have a lot of those patients’ voices who are out there telling their stories and calling for more action to combat antimicrobial resistance.
I think that’s something that’s changing slowly. ?
I think we’ve reached a time in society where you’d be hard-pressed to find someone who couldn’t tell you a personal story or have a family member whose life has not been touched by the problem of antimicrobial resistance. And I think we need to convert that level of commonality of antimicrobial resistance to action, to getting people more interested in figuring out ways that we can combat the problem.
? Do we have enough data about this problem? Is our surveillance good enough about antimicrobial resistance and particularly about some of these Gram negatives that have been a real problem in recent years? ?
? We know this is a problem today. We don’t need more evidence of that. At least certainly I don’t, and I don’t think most other public health officials do. We also know a lot about what we can do to address the problem. Could we know more? Of course we could. We could always benefit from new strategies.
But we know a lot of things that work now. We know that we can improve the use of antibiotics. We know that we’re not doing what we should be doing. We know that today in our clinics and in our hospitals, up to half of all the antibiotics that are prescribed ? up to half in some studies ? are either unneeded or patients are getting the wrong drugs to treat their infections. So we know we can do better than that.
We have lots of good examples where we use antibiotics better, yet we’re not doing it everywhere. We know we can prevent the spread of these infections in our hospitals, yet time and again, when we do these investigations and we talk to the hospitals, people are not doing the simple things. They’re not washing their hands. They’re not wearing the gowns and gloves when it’s recommended. ?
? A lot of people have said to us there’s not that same kind of surveillance when it comes to antimicrobial resistance. ?There’s not really a way to understand the spreads throughout the whole country to this particular problem.
I think we definitely need to do a better job of improving the way we monitor and track not just antibiotic resistance but also antibiotic use. ?
Historically, we at CDC have had little if any information on how antibiotics are being used in our hospitals and other health care settings.
So there is a definite need to bring the surveillance of both antimicrobial resistance and antimicrobial use into the modern era, and that means we need to do this electronically. We can’t rely on the paper-based reports and those kinds of paper-based systems that we have historically been using a lot of to do this type of surveillance.
So what we’re doing at CDC is now working very hard to try and harness the power of electronic information, to revolutionize the way we do surveillance for antimicrobial use and antimicrobial resistance.
The way we’re doing that is we’ve developed two different parts of our national system that we use to track infections in hospitals. It’s called the National Healthcare Safety Network [NHSN], and that now has a new part of it that’s called the Antimicrobial Use [AU] Module.
It’s kind of a trial right?
It’s a system that’s up and running. ?[It] is a system that allows for completely electronic capture of the antibiotics that are being used in a hospital. ?It sends it to us at CDC, but most importantly, it gives it back to the facility in real time.
It’s a relatively new system and [used at only] a small number of hospitals.
It’s a very new system. Enrollment is growing, but it is small right now. And so it’s something that we’re really trying to raise awareness of to get more hospitals to enroll in the system.
The other change that we’re developing is something called the Antibiotic Resistance [AR] Module of this network, this surveillance net.
?We’d like to have an even fuller picture of antibiotic resistance in our hospitals in the United States, and so what we’re doing is developing a fully electronic system that will extract electronic information on resistance from hospitals and summarize that information and provide it simultaneously both to the health-care facility where the information comes from and to CDC.
That module, which will be launched we hope in the early part of next year, really will be a giant step forward. It will be transformative in our efforts to monitor resistance. It will take us out of the old model, which was doing this manually, trying to collect all this information from a variety of different laboratory systems, and take us to a position where we can do that electronically.
? I’d like to ask you about the use of antibiotics for farm animals. I know a large share of the antibiotics produced in this country is used in agriculture. Do you see problems there? Is that generating resistance as well as the use for humans?
We know that the use of antibiotics in any setting, and especially the overuse of antibiotics in any setting, is an issue that will generate resistance, that will lead to problems of resistance. That applies as much for human use as it does for animal use.
Do you think that if they’re used for animals, there’s actually a pathway to resistance that is a threat to human health?
I think there is. There have been a number of studies that show that when you give antibiotics to animals, especially to animals that we then eat, there are antibiotics that get into their systems that can develop resistance, and then when we eat the food, we can be exposed to those resistant organisms.
We also know that if antibiotics are used in animal feed that they can end up in animal waste, so we can end up with antibiotics in our water supplies, and it’s that type of low-level presence of antibiotics that can also lead to issues with resistance. ?
Do you think we have enough data to know what’s happening with the antibiotics used on the farm?
? I think we know enough to say that we need to be doing a better job of improving appropriate use of antibiotics in all sectors, humans and animals.
But the agriculture sector is different, because antibiotics have been used there for a long time with an eye toward improving the growth of the animals, really for food purposes, to make them bigger and fatter with less food. Does that concern you as a use?
Certainly the CDC believes quite firmly, and I think there are a number of veterinary experts here and in other places who agree with the stance that we should never be using antibiotics in agriculture or in people for any other purpose than to treat infections.
Using antibiotics to promote growth in animals is not a good use of antibiotics. It’s not careful use of this really delicate and invaluable resource. ?
? Do you think that it’s fair to say that we’ve had a failure of capitalism here?
?The fact that these are for-profit companies that we asked to develop drugs for us, then it should come as no surprise to us if the drugs that we’re asking to develop don’t make money that they’re not going to invest a large amount in making new ones.
So in a sense, I think it’s going to call for a different approach when we’re talking about drugs that really are critically important to society. They’re a shared resource. Antibiotics are different than any other drug that we have.
Why do you say that?
If I overprescribe a drug to treat high blood pressure, if I give it to too many patients, it’s a problem for those patients and for the people who are paying for those patients to get the drug, but it doesn’t create any problems for other patients.
If I give my patients too many antibiotics ? say I am in a hospital, working in a ward, and I create resistant organisms in my patients, those organisms can then be spread to other patients on the ward. My patients can leave the hospital and take those organisms to other hospitals. So I as one individual, with my prescribing pen in one hospital, can create a problem for a very large group of individuals who I’ve never even met. ?
They’re in a way a public resource, so we have I think a responsibility ? to steward that resource effectively, much like we do natural resources.
There were a lot of people who have said that we really should think about antibiotics the way we think about the environment. We all share the air we breathe. If I pollute the air, it has a negative impact on you, just like antibiotics. If I misuse antibiotics, it can have a negative impact on you.
? Should we change the way we produce them?
?I think this is clearly an area where drug companies have to remain active. They’re the companies that bring these drugs to market. They make them. They produce them. They know how to do this kind of research. But we can’t rely on them exclusively to do this work.
We have to view this as something that all of us bear a stake in, so that means we may need to explore ways that we can have better public-private partnerships to develop new antibiotics, to bring them to market. So I think it calls on a new model to develop new antibiotics.
Does a new model mean that we may need to change the pricing structure? Some people we’ve talked to say that for many, many years, antibiotics were relatively inexpensive compared to blockbuster drugs for chronic conditions and diseases. Do we need to make them more expensive? Is that plausible?
I would say that that model has already changed. If you look at new antibiotics now, they are very expensive. And that’s a reality of developing these very, very difficult-to-develop and expensive drugs.
So I think as new agents are developed, they are going to be expensive, which I think will call on us to steward them carefully, to use them wisely, and then administer them effectively.
? Do we need to change the regulatory pathway for new antibiotics? Would that encourage more drug development?
There’s a lot of discussion about ways that we can change the approval process for new drugs in order to try and get these drugs to market faster, because there’s an urgent need, we know, to get these new agents on the market, and we know our current approval process is a slow process. It’s designed to deliver safe drugs to the public.
There’s a need, though, to balance that safety with speed, and that’s a difficult balance that we have to strike. But I think there are a lot of discussions that are ongoing about how we might work to speed up the approval of new drugs, perhaps in a very limited way, so that we can at least offer them to the patients who have no other options. ?
Does that mean, though, relaxing regulatory controls?
I wouldn’t say it’s relaxing regulatory controls, because I don’t think anyone wants to accept drugs that are not safe.
I think anytime we administer a drug, there is a risk and a benefit. We know that every drug has side effects, and we know that every drug has benefits to the patient. So we may need to enter a situation where for a limited group of individuals who are at very, very high risk of dying from their infections, they have very serious infections, we may need to approve for them or allow them to use drugs that have more side effects.
It’s akin to what we do now in chemotherapy. We know that there are chemotherapy agents that have a lot of side effects, but we allow them to be used in limited ways for patients who don’t have other options for them. And I think that’s the same type of model that people are talking about exploring for antibiotics.
? When you think about public policy ? what needs to be done that is not being done? ?
I think there’s action in all of the areas where there needs to be action. The issue is that we need a lot more of it. We need to better understand the problem. We’re developing the tools that will help us do that, but it’s not enough to simply develop tools. People have to use those tools. ?
And it’s not easy to do. There are a lot of things that we ask of our physicians, our nurses, all of our health care providers. We ask them now to use antibiotics wisely, to wash their hands, to wear gowns, to wear gloves, to test their patients for these agents. It’s a lot, but it’s incredibly important.
So in other words, it’s one thing to set the rules, but it’s another thing for people to follow them.
That’s exactly right.
And you don’t feel that they’re following them.
?We’re not doing it enough. We know that there’s a lot of overuse, of misuse of antibiotics, and what’s discouraging about that is it’s been an issue for a very long time. This is something that if you look at data over time on people who have assessed what percentage of antibiotic use is not optimal, that percentage hasn’t moved very much. It’s ranged from 20 to 50 percent in studies from every decade where they’ve been done, the ’70s, the ’80s, the ’90s, even now. So we know that there is substantial room for improvement.
Given the threat to public health that you’ve described, do you think we need a more forceful response on all different fronts?
I think we do, and I think that that’s something that we have to consider. ?
We talked earlier about the need to break the mold, to do things in a new way, and one of those ways might be new ways to tackling some of these issues, to make things that are voluntary now not voluntary.
One of the challenges, of course, is anytime you talk about new regulations, there are always costs and expenses and unintended consequences, and that doesn’t mean that we should never have new regulations. What it means is that we need to work together, both as people who write regulations and as people who will have to follow them, to figure out what are the right types of regulations that might get us progress on the directions we need to go.
Some people we’ve talked to said about the Interagency Task Force that it’s worked for a decade, but in that decade, the problem of resistance has grown more severe, and some of these people said it hasn’t really done a thing. Could you respond to that?
I think that no one would say that the creation of a task force was the necessary step to tackling the problem of antibiotic resistance in the United States. I think it was a necessary step in the right direction, but it’s certainly not sufficient. ?
At the end of the day, what we really need is specific actions to be taken, and that’s not just on the part of the government. It’s actions across the front from all stakeholders who are threatened by this problem of resistance.
So the task force has been effective in some areas, but the goal of the task force, the purpose of the task force, was not to create a committee that was going to solve the problem of antibiotic resistance. The purpose of the task force was to try and lay out the actions that need to be taken to get us where we need to go. But there are a lot of groups that are going to have to be involved in taking those actions.
It sounds like you think that there is a crying need for leadership on this subject.
I think the crying need is for action. ? Everybody has to step up. I think that’s one issue they talk a lot about, the tragedy of the commons, where if you have a common resource, nobody thinks they own it, so we all tend to overuse it.
We don’t need leadership from one person to stand up and say, “I am the leader who’s going to solve the problem of antibiotic resistance.” This is an issue where everybody has to step forward. Every provider has to become a leader in this way. Every person who prescribes antibiotics has to do so responsibly.
You’ve described a very diffuse arrangement, where lots of people are working on it. But would it help, like it has on other diseases and other crises, if there was one person in charge, a czar at the department who could coordinate and be in charge of the subject?
? Appointing one person is not going to solve the issue of antibiotic resistance in the United States. Having a single person who is the “resistance czar” is not going to solve the problem of overprescribing of antibiotics or of people not washing their hands after they care for a person with a resistant infection.
In fact, what we’ve found in a lot of our work is that it’s leadership at the local level which can make an even bigger difference. It’s local leaders, it’s leaders at the hospital, taking these types of actions that are oftentimes much more effective in getting people to do what’s really necessary to be done. ?
When I look at the Department of Health and Human Services, for example, I look at the assistant secretaries, there’s not an assistant secretary who deals with anti-microbial resistance. There is, for other kinds of health problems. It seems that this is a problem that hasn’t actually registered in the high levels of the government. It’s a crisis, you said.
It is a crisis. It’s indeed a crisis. There are a variety of different issues that have to be addressed. They require a variety of different actions by all of the different federal agencies who are involved in this.
? But when you think about the history of health care crises in the last generation, our system is a political system, and there are competing battles for resources and for time. Look at how we responded to HIV/AIDS. It wasn’t done at the local level. It required somebody to say, “We need to do this.” It’s fought in budgets. It’s fought in organizations. And you don’t seem to be wanting to look at those problems. If we have a nightmare bacteria and public health crisis, it seems to me that you’re setting it up as a big problem but not thinking about the response in a big way.
I disagree. I think there is a tremendous amount happening at the national level. There’s better surveillance. There’s more investments in research. There’s explorations of new drug-approval pathways. There’s all of these actions happening at a large level.
But HIV/AIDS is a great example. There was action that was required at the federal level with respect to developing new drugs, but then we also had to have behavioral change, which required action at the local level as well. So no amount of policy changes could alter the way that people were behaving that were putting some people at risk for getting HIV.
So you have to have both. You have to have policy writ large. You have to have active government involvement, and I think there is that. But we also have to have leadership and involvement, engagement and action at the local level. You can’t have one without the other because either is ineffective without the other one.
If you’re talking about changing public opinion and the way people behave, doesn’t that really require leadership and an outspoken voice at the highest level?
I think it does, and I think we do have that. The director of our agency is, I think, the leading voice on health who people turn to and trust, and he has spoken up in a very loud way about this issue. ?
But then we also have to have a doctor at the local hospital who’s going to stand up and say: “That’s right. In response to that, I want to implement a policy in my hospital. I want to change the way that I use antibiotics and my colleagues use antibiotics.”
So it requires leadership writ large at the highest levels, and it requires leadership at all of the local levels, and it requires follower-ship, if you will. People have to be willing to change practices that have been unchanged for a very long time if we’re really going to get to a solution on this.