Policy Approaches to Containing Antimicrobial Resistance

ROBERT JOHNSON:
This is Public Health Review, I'm Robert Johnson.

On this episode, the fight against bacteria too tough to kill—

DR. ARJUN SRINIVASAN:
Antibiotic resistance really fundamentally threatens the delivery of modern medicine.

JOHNSON:
—a recognition that the stakes are high—

DR. THOMAS WILLIAMS:
If you can prevent one death or one case, that's worth doing.

JOHNSON:
—and Nebraska's plan to defend public health.

DR. MAUREEN TIERNEY:
Seeing what happened in the states where it's really common, particularly in the mid-Atlantic and North Atlantic states, made everybody in the rest of the country say we really need to take notice so we prevent a similar problem where we are.

JOHNSON:
Welcome to Public Health Review, a new podcast brought to you by the Association of State and Territorial Health Officials. With each episode, we will discuss the most pressing public health issues facing our states and territories and explore what health departments are doing to improve the condition of our country's most vulnerable populations.

This time, we're tracking the challenge of antimicrobial resistance, or AMR, and the worst of them all—so-called nightmare bacteria. We'll explore Nebraska's efforts to get ahead of the problem later.

But first we get an overview of the challenge and a briefing on an April 2018 CDC Vital Signs report coauthored by Dr. Arjun Srinivasan, the associate director of the Healthcare-Associated Infection Prevention Program within the National Center for Emerging and Zoonotic Infectious Diseases at the CDC. Dr. Srinivasan begins our conversation with a few important definitions.

SRINIVASAN:
When we talk about resistant bacteria in the broadest of all possible terms, we are simply referring to bacteria that do not respond to the recommended antibiotic, and so they can't be treated with the antibiotic that the clinician would normally prescribe to treat a particular infection.

And what that means is that the clinician is left having to pick a different, an alternate, antibiotic, and sometimes that means it may be one that has more toxicities, more adverse effects. It may be more expensive. In some cases, that means they're sometimes less effective. And in rare instances, it actually means that there are no options at all.

And so, we do see infections in the United States where clinicians really have run out of good treatment options for their patients. So, it's a broad term—antibiotic resistance—but basically means that your options to treat are limited in some way.

JOHNSON:
And the definition of nightmare bacteria?

SRINIVASAN:
You know, that's a term that's been coined. It doesn't have an official medical definition, and so every provider I think probably has a slightly different terminology for it.

But when we think about that term—and it was coined by our former director, Tom Frieden, and I think he was using it to describe these bacteria, things like the carbapenem-resistant Enterobacteriaceae, or CRE, which is a major focus of our prevention efforts now—and I think he coined that term because he said, "Look, here is a bacteria that is really resistant to antibiotics. There are very, very few options to treat these patients."

Patients who get infections with these bacteria—if you get this bacteria in your bloodstream, the mortality is very high—half of those patients die from these infections. And the bacteria can spread from person to person, and the resistance genes that confer that resistance can also be spread. So he said, you know, "Here you've got this incredible threat on so many fronts and this is, from a clinician's perspective, this is a nightmare."

JOHNSON:
You are the co-author of a CDC Vital Signs report on the containment of nightmare bacteria. Can you tell us why you and your colleagues wrote this report?

SRINIVASAN:
Absolutely. The MMWR report on containment was really meant to highlight and summarize our experience with this new approach to addressing the problem of antibiotic resistance.

You know, Robert, in the past with antibiotic resistance, we would wait until we had, you know, an outbreak of several cases or until a problem had gotten to a certain point before we would really jump in and react. And I think what we recognized over time is that, you know, the earlier we can intervene on something, the more effective our interventions might be.

And in the report, we actually do compare and contrast two different experiences: one in the past where we didn't really initiate an early and aggressive response to a new resistance threat—and that was back in the eighties; and, more recently, we summarize what happened with these carbapenem-resistant Enterobacteriaceae—or CRE—or the nightmare bacteria as they've been described. And for CRE, we really did implement a much more aggressive response fairly early on in the development and the recognition of CRE, and what we saw is that early response seemed to contribute to a decrease in CRE that we did not see for the older type of resistance, the so-called extended spectrum beta-Lactamase resistance.

And so, it's a suggestion that if we intervene early, we might have an effect on resistance, and that really led to the development of this containment approach, which is what if we were even more aggressive? What if, rather than responding early, what if we're responding to the very first case, the very first time or times that we saw a resistance that we hadn't seen before? What if we went in aggressively and we looked at the infection control practices at the facility, and we did some contact investigations of patients around that index patient, and really put an aggressive effort in place to contain that resistance at the very first occurrence?

And that's what this new strategy is. The report that summarizes our initial experience with that strategy, where we did find these really novel resistance threats over 200 times in healthcare facilities throughout the United States. And we did execute a really aggressive response to this resistance at its earliest occurrence.

JOHNSON:
Can you take us through the five steps of the containment strategy?

SRINIVASAN:
Absolutely. So, there are multiple steps in containment, and they really kind of boil down to the early detection of the organisms. And this obviously requires some new capacity in order to be able to do that type of detection. So, we have now a network of labs in the United States called the anti-microbial resistance lab network, and it's a group of labs. There's a lab in every state, and then there are seven regional labs throughout the country. And so, now there is this capacity to do this early detection out in the field, right on the front lines in every state. You know, in the past, all of the samples had to come to CDC in order to be tested, and now we've pushed that capacity out into the states. And so, early detection is one of the key components.

The other—another key component is the ability to respond. And so, you know, it's not just enough to detect resistance, you have to respond to it. And so, now every state has staff that are trained and are experts in helping healthcare facilities respond to these, this discovery of this novel resistance. And so, they are trained to go in and look at practices for what we call infection control—how good a job are you doing at making sure that this resistance doesn't spread. They can work with the lab in the hospital to make sure that they are optimized to detect the resistance.

And so, that is a capacity where the health department is able to assist the healthcare facilities in responding. And then, we recognize that this is a continuous process, right? We have to keep doing this work until we've got the pathogen contained. And so, detection and response needs to continue until there is no more transmission of the organism.

And so, that's really kind of the crux of what this containment response looks like on the front lines.

JOHNSON:
It sounds like there is a lot of work going on behind the scenes. That makes me think this is an issue that's a little more urgent than I might've thought otherwise.

SRINIVASAN:
We think this is an urgent issue.

You know, antibiotic resistance has been identified as one of the urgent threats to human health, not just in the United States but globally; and it's important for a couple of reasons.

Of course, it's important because these resistant infections make people sick: they can prolong hospital stays; in the United States, we estimate that 23,000 people a year die from these resistant infections. So, there is really important morbidity and mortality that goes with these infections. And so that, you know, in and of itself makes this an urgent public health and clinical issue.

But the other thing that's really important is that antibiotic resistance really fundamentally threatens the delivery of modern medicine. So much of what we do in modern medicine depends on our ability to treat infections effectively.

And what I mean by that is to think about things like joint replacement surgery, where we give antibiotics before we do the surgery because we are worried about the potential for developing an infection. Think about an organ transplant, where we will suppress the patient's immune system so that they can accept that donated organ. Think about cancer chemotherapy where the drugs that we give weaken an immune system.

So, all of these advances in medicine depend on our ability to treat infections that might occur effectively. If we lose the ability to treat infections, then we risk losing our ability to perform some of these modern medical treatments that we all now really take for granted.

JOHNSON:
Is the problem on the rise? Are we seeing more of these cases? Is that why it's become so urgent?

SRINIVASAN:
The problem has gotten worse over time. You know, resistance tends to develop and then increase over time. We are in the process now of looking to see, you know, where things are. We issued a report in 2013 on the current state of the burden of antibiotic resistance in the United States, and we are in the process now of looking at those numbers again.

But historically, we do know that this is a problem that tends to get worse over time unless aggressive action is taken. The good news is that, as we showed in that morbidity and mortality weekly report that we published, there is the ability to put the genie back in the bottle, so to speak.

With this aggressive intervention that we did for carbapenem-resistant Enterobacteriaceae, or CRE, we have over time actually seen a decrease in that resistance. And so, that's a really encouraging finding, for us to know that the increase in resistance is not inevitable. It is that we can address and make resistance go back down if we implement these aggressive and coordinated responses.

JOHNSON:
Is the problem confined to hospitals or centers where surgeries are occurring, or is it more widespread than that? Can you pick this up anywhere?

SRINIVASAN:
Yeah, that's a really good point to emphasize. A problem is not limited to any one particular healthcare setting—you know, antibiotic resistance as a problem, really it's a problem everywhere.

So, people have probably heard about infections with methicillin-resistant staphylococcus aureus, or MRSA or "mersa". That has been an issue in gyms and locker rooms. There are problems and challenges with a drug resistant neisseria gonorrhoeae that, of course, occur out in the community.

But some of the things that we really talk about, these nightmare bacteria, these very, very resistant pathogens, they do tend to be seen much more commonly in healthcare settings, mostly in acute-care hospitals and also in nursing homes.

So, they are seeing them throughout the healthcare delivery system; but antibiotic resistance is a problem that really knows no boundaries and no borders.

JOHNSON:
Who should take note of the report, and what do you think they should do with the findings?

SRINIVASAN:
You know, we really hope that the report will speak to both the public health community, so that our colleagues in state and local health departments will be aware of this containment strategy because they are so fundamentally important in executing this strategy. And we hope that they will see this and see kind of all of the different things that are both available to them and all of the different places where they can serve such a critical role.

And we also hope that our clinical colleagues will read this report and be aware of the problem of antibiotic resistance, and also now be aware of this new response capacity. You know, the containment approach only works if clinicians send these bacteria to the state lab when they're suspicious. And so, all of the containment responses have to begin with a clinician saying, "Wait a minute, this organism has really resistant. We haven't seen something like this before. I'm going to send this to the lab to test it to see if its one of these organisms that requires an aggressive response."

JOHNSON:
Our audience is largely made up of public health professionals, but occasionally there are people out in the general public listening.

Do they have a role in helping contain these bacteria, or is this left to the public health and the professional health community?

SRINIVASAN:
You know, everybody plays a role. If you are a member of the general public, I think that is really important to be informed and aware of this problem of antibiotic resistance, and important to know the types of things that you can do to keep yourself healthy. You know, we always say that if you don't get an infection, you won't be at risk for an antibiotic-resistant infection.

So, doing those simple things to keep you healthy—you know, cleaning your hands regularly, covering your coughs when you have a cold, getting your influenza vaccine—all of these are the types of things that we can do to keep ourselves from getting an infection or from spreading infections. And those are all things that are useful in our efforts to combat antibiotic resistance.

JOHNSON:
You noted that progress is being made. So, what's the prognosis going forward?

SRINIVASAN:
You know, I think we are cautiously optimistic. We have put into place a response, a testing and response infrastructure, that we hope will help us get ahead of this problem. And we know that this is a situation that is going to require continued vigilance. We have to continue to do these responses.

We, you know, we are not in a place where we can just rest and say, "Okay, well, this problem is solved. We don't have to continue to really aggressively work on it."

But we do believe that this new containment approach will help us get ahead of the problem of antibiotic resistance.

JOHNSON:
Given a serious threat of antimicrobial-resistant bacteria and the importance of keeping resistance from spreading causing hard to treat or even untreatable infections, states and territories across the nation have taken decisive action, Nebraska among them.

Dr. Thomas Williams is the state's chief medical officer and director of the Office of Public Health. His view: the investment of time and effort is well worth it.

WILLIAMS:
If you can prevent one death or one case, that's worth doing; and I think that the likelihood of preventing more than that is significant in the state. And so, it's very positive.

JOHNSON:
On December 27, 2016, Nebraska governor Pete Ricketts approved changes to state law requiring that nightmare bacteria cases be reported within 24 hours of infection.

Dr. Maureen Tierney is Nebraska's healthcare-associated infections coordinator. She's been driving the program that started with the reporting rule and CDC's containment strategy.

TIERNEY:
We followed the CDC framework, and having that framework adds legitimacy to what we've done; and then we personalized it or individualized it a little bit to underscore the way things happen in Nebraska. And, you know, we have a lot of very small hospitals here. So, in addition to our large academic medical centers, we wanted to make sure we have a protocol that could be rolled out in all types of facilities.

But we have guidelines for the reporting—the detection, reporting, and containment of CRE that contain all of the CDC elements, plus a few of our own.

JOHNSON:
Now, requiring a facility in a state to report an issue within 24 hours is going to generate data and paperwork, I assume.

How did you deal with all of that? How are you dealing with that now that you're, what, about a year and a half into this?

TIERNEY:
Well, thankfully most of the laboratories in Nebraska report their data via electronic lab reporting—or ELR—and we are able to review electronic lab reporting data at the state on a daily basis. So, that helps a lot with removing the paperwork part and making it electronic.

However, the ultimate responsibility for reporting lies with a physician for any patient who will have a condition on the reportable disease list. But because it's pretty complicated—once we actually find someone—if someone has CRE, what we want to do to contain it.

So, not only do we review those electronic reports, we ask facilities to call us; and then Dr. Caitlin Pedati and myself work very closely with any facility as to what the next steps have to be.

JOHNSON:
And you've been at this again about a year and a half, right?

TIERNEY:
Correct.

JOHNSON:
How is it going?

TIERNEY:
I think it's going really well.

It's complicated because what we need to do anytime we find someone with CRE—and, in particular, with a certain kind of a CRE called CPCRE—so, what we do is work with an infection preventionist inside of a facility to say, okay, who would that facility would potentially be most likely to have to also be colonized with this organism as a result of interaction with the what we call index case or individual.

And so, that process can be pretty time consuming and sometimes confusing; but we have a good system and very good support from the Nebraska public health laboratory in doing this. And so, I think that it's really flowed out—I wouldn't say seamlessly, by any means—but I think we've been able to accomplish it each time we've been challenged.

JOHNSON:
Are the people on the front end of this process—the physicians—are they cooperating?

TIERNEY:
Very much so. And, as a matter of fact, I think because it's something that all physicians or nurse practitioners or PAs understand is, you know, can have very serious consequences. They actually welcome their interaction with us.

JOHNSON:
And the system—it sounds like, because it's electronic—is going to at least make the data entry piece of it not as difficult as it might've been the old fashioned way, I assume.

TIERNEY:
Well, you know, when we come to the outbreak part, so when—not the reporting of the laboratory report and then some of the particular data about the patient, 'cause anytime there's a lab entry for a particular laboratory test, that will include a fair amount of patient information—but the next part, the outbreak investigation protocol—and we have this on our website, and it follows many of the CDC guidelines—there's a lot of additional information that we are collecting about where the patient is in the hospital, who their roommate was, who were the other patients on the floor.

That information we actually still collect by hand.

JOHNSON:
How did you get everyone ready for this? Did you conduct trainings or just provide information online? What was the process, in that regard?

TIERNEY:
We did a couple of things. We sent out a health alert letting everyone in the state know that this condition, as well as a few other conditions along with it, had become reportable and had been added to that list. We have put all of this information on our website.

So, in addition to stating that and describing CRE, we have links to all our guidance documents and outbreak protocol documents. We held a conference calls with the laboratory network around the state.

And lastly, we have held training and given talks on this. Probably the best example is the NIC—Nebraska Infection Control—network has two separate trainings for infection preventionist practitioners in the state. And we held sort of a walkthrough, a containment workshop, for CRE last May, and then—I mean this last September, and then again just a few weeks ago in May—and walked through a scenario of someone in their facility who might all of a sudden have a culture with this organism and how they would have to work through that in a team way with members of my team.

JOHNSON:
So, you have the rule in place and the 24-hour clock is ticking when a case is identified. What happens in Nebraska at that point?

TIERNEY:
Once we've identified a case, and this happens similarly in many states, when we have a case of CRE—not all CRE are the same, some are more concerning than others, depending on the mechanism of resistance—so, that lab specimen is sent to one of two labs in the state that have the capacity to detect the more concerning type of resistance called carbapenemase production. Once we identify that we have what's also known as the CPCRE, that information is immediately sent to either myself or one of the individuals on my team.

We call the facility that's involved and talk with the infection preventionist at that facility to try and get the information about who would be at risk for colonization with this organism as a result of their connection with this index case. And so, we talk for an hour, an hour and a half, to fill out the investigation form. And then, if we suspect there is certain people we think would be at risk—so, the individual was in a room with two other people and was next to a room with another two other people for a week, let's say—we then have those people are then screened, which actually means they have a rectal swab taken. And those are actually sent to the Nebraska public health laboratory for further testing to see if indeed they may have been colonized.

At the same time, the index person is put under contact precautions—which means gloves and gowns for any contact and, if possible, placed into a private room—so that, from that point on, no one would be at risk of obtaining this organism.

JOHNSON:
Has this new approach discovered or turned up any new cases that you think might have slipped through otherwise?

TIERNEY:
In one instance, it did. It turned up one additional case that we might've missed. See, we're still in the hope we haven't had too, too much of this and we want to keep it that way.

So, thankfully we haven't had settings where you've had a widespread outbreak or multiple, you know, other folks obtain the organism. But in one case, we did find a case that we might not have found otherwise.

JOHNSON:
I mean, it is one of those stats, right, you want it to be as low as possible. You want to know that your net is tight. But at the end of the day, you don't want to find any issues.

TIERNEY:
That's correct.

JOHNSON:
So one case then would be a success, then, I would think.

TIERNEY:
Yes, I would think so.

JOHNSON:
Can you talk to me about some of the other things that you've done?

You worked pretty hard to get the governor to sign a proclamation on this issue. Why did you think that was important as part of your overall strategy?

TIERNEY:
It's definitely been shown that the more antibiotics we use, the more likely bacteria will develop resistance. And so, having everyone understand that you only want to give antibiotics for the right reasons is really important. And, in general, I think for years many folks in the public have felt that if they were ill with certain conditions and they went to the physician, that an antibiotic will always be the answer and didn't sort of understand that the antibiotics aren't always the answer.

And as a matter of fact, the antibiotics can cause problems, not only with resistance in general but can also cause side effects such as Clostridium difficile infection, or allergic reactions, or even some other side effects. And there was often a lot of pressure for physicians to prescribe antibiotics when maybe they weren't necessary.

So, really understanding not only from the professional side, but also the public side that, you know, antibiotic use really needs to be for the, you know, the right drug for the right reason for the right amount of time was really the way to go. So, we wanted to make sure that the public became more and more aware of this.

So, that's the reason I really wanted the governor to sign this proclamation and for us to have an antibiotic awareness week in Nebraska to try and make that point.

JOHNSON:
Explain the partnership with the University of Nebraska Medical Center. What is that about and how does it fit into the plan?

TIERNEY:
We are really proud of our public-private partnership with UNMC, and sometimes I actually call it a public-public-private partnership because the University of Nebraska Medical Center is part of the University of Nebraska system. Nebraska Medicine, which is the clinical hospital connected, is more on the sort of private side. So, it's a little different than your typical public-private partnership.

But we have sub-awarded with a group at Nebraska Medicine called ASAP, which stands for Antimicrobial Stewardship and Assessment—I'm sorry, Antimicrobial Stewardship Assessment and Promotion program.

And Nebraska Medicine and UNMC have been leaders in antimicrobial stewardship for quite time. They've had a really terrific program and there was so much work to be done. It was not something that we alone could do without getting involved with someone else; and the program that they have created, which works with facilities to try and improve and mentor antimicrobial stewardship, creates educational tools and a website that is really tremendous in the resources and guidelines that it provides for local facilities.

We are really proud of that program, and they've done a wonderful job.

JOHNSON:
So, they reach out and work with the facilities around the state to teach them how to contain these problems, or identify them, or all of the above?

TIERNEY:
Well, their primary role is on the stewardship side, so it's actually more preventing the resistance from happening. The actual detection and containment, that's more the team that's at the state department of public health.

But what we want to see in the longer run is less resistance overall. And so, really helping guide facilities—particularly smaller hospitals, and maybe not as small as acute-care hospitals, but, you know, smaller hospitals may be a hundred beds; then your critical access hospitals that are less than 25 beds, there are 65 of those in Nebraska; and long-term care facilities—understand the principles and the practices of antimicrobial stewardship so that they can then, in their facilities, overtime develop less resistance because they are using antibiotics only when they're necessary. And if you use antibiotics only when necessary, you can usually drop your overall antibiotic use by at least a third, if not more.

JOHNSON:
You've got your rule for reporting within 24 hours. You have your process for handling those reports when they come in. You've got your public awareness through the help of the governor's office. You've got your relationship with a university, out teaching hospitals and their teams how to not get into this position.

What's left to do?

TIERNEY:
Although we've done a lot in all those areas, within each one of those things that you mentioned we could probably do more. For example, one thing we want to do next year is during—and the antibiotic awareness week nationally occurs on a yearly basis, and we'd like to have it occurred on a yearly basis in the state—and next year, we actually want to go into middle schools or high schools—middle school is one year, high school is the following year—to teach about antimicrobial stewardship, and also a bit about transmission of resistant organisms.

In terms of teaching antibiotic stewardship, I think the next—we haven't been able to have as much of an inroads into outpatient facilities, urgent care facilities especially, and some long-term care facilities. So, I think that's our next reach.

And then the last thing, which refers back to some of your original question in terms of containment, is the CDC and their containment protocol talks about screening folks when they enter a hospital or long-term care facility who might be a high risk for some of these resistant organisms. So, to try and figure out who those folks might be and screen them so that, upon admission, it's detected as opposed to finding out a week after they've been there.

JOHNSON:
For more information about the fight to contain and control drug-resistant bacteria, visit the ASTHO website. You can also visit the CDC site to read the Vital Signs report. Nebraska's work is available on the state's website as well.

The links to these resources are in the show notes.

Thanks for listening to Public Health Review. Because of your support, our audience is growing with each episode. If you enjoy the program, find us on Apple Podcasts where you can subscribe, listen, and write a review.

If you have comments or questions, we'd like to hear from you. Email us pr@astho.org—that's PR at ASTHO dot org.

This show is a production of the Association of State and Territorial Health Officials.

For Public Health Review, I'm Robert Johnson. Be well.