Call Transcript: CRE and C. difficile : Is Your Healthcare Facility Implementing the Necessary Approach to Stop the Spread?

Coordinator:
Thank you for standing by.At this time all participants are in a listen-only mode. After the presentation, we will conduct a question-and-answer session. To ask a question, please press the star 1 and please record your name. Today's conference is being recorded. If you have any objections, you may disconnect at this time. I would like to introduce your host for today's conference. And Dr. (Khan) you may begin.

Ibad Khan:
Thank you, (Kathy). Dr. Arjun Srinivasan please give your message.

Arjun Srinivasan:
Yes, hi this is Arjun. We'll be getting started in just a second. We've got a few housekeeping details we'll go through before we begin the contents of the call. But I would like to ask everyone who's signed in via the webinar is able to participate in a poll. You should see a poll question on your screen right now, what practice type describes you best. We thought it would be interesting for all of us to see who we've got on the call today.

So if you are signed in via the webinar and you see that screen, please do go ahead and vote while we're doing some of the introductory work. (Ibad Khan), you want to take it away with the introductions?

Ibad Khan:
Thank you, Dr. Srinivasan. Good afternoon. I'm Ibad Khan, and I'm representing the clinician outreach and community activity COCA with the Emergency Risk Communications branch at the Centers for Disease Control and Prevention. I am delighted to welcome you to today's COCA call, CRE and C. Difficile: Is Your Healthcare Implementing the Necessary Approach to Stop the Spread. Free continuing education is offered for this call. Instructions on how to earn credit will be provided at the end of the call.

CDC, our planners, presenters and their spouse's partners wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters, with the exception of Dr. (Cosgrove). She would like to disclose that she is a consultant for Novartis as a member of an external infection adjudication committee and has received grant funding to her institution, Johns Hopkins University from Pfizer grants for learning and change.

Planners have reviewed content to ensure there is no bias. This presentation will not include any discussion of the unlabeled use of a product or products under investigational use.

At the end of the presentation, you will have the opportunity to ask the presenters questions. On the phone, dialing star 1 will put you in the queue for questions. You may submit questions through the webinar system at any time during the presentation by selecting the Q&A tab at the top of the webinar screen and typing in your question.

At the conclusion of today's session, the participants will be able to discuss the current state of antibiotic-resistant bacteria in US healthcare facilities, identify mechanisms that can be used to identify gaps in antibiotic stewardship, and help to charter a course of action to decrease the spread of antibiotic-resistant infections, describe how healthcare organizations and public health can collaborate to stop the spread of antibiotic-resistant germs and C. difficile in facilities.

At this time I would like to introduce Dr. Arjun Srinivasan the Healthcare Director for Healthcare Associated Infection Prevention Programs in the Division of Healthcare Quality Promotion at CDC. Dr. Srinivasan will provide an overview and introduce the presenters for today's call. At this time, please welcome Dr. Srinivasan.

Arjun Srinivasan:
Thank you, (Ibad), and thank you all of you for joining this COCA call today. I'm very pleased to be with you, and it's my pleasure really to introduce the other speakers, Dr. (Robert Weinstein) from Illinois, and (Sara Cosgrove) from Maryland, both of whom I think will provide some really great insights into the types of things that we can work on today in order to address the challenge of antibiotic resistance.

Well, all of you are here today because you are very well aware of the problems posed by antibiotic resistance in the United States. We've got data that we published from the CDC where we estimate that antibiotic resistance impacts more than 2 million people every year in this country, and we think that the number of people who die from complications of these infections could be as high as 23,000.

And additionally, we know that there are a large number, about half a million cases every year, of Clostridium difficile on top of these cases of antibiotic-resistant bacteria, which are of course driven by the same types of problems that breed antibiotic resistance: poor infection control practices, transmission of organisms, use and overuse of antibiotics.

And we know that the economic and clinical impacts of antibiotic resistance are truly staggering. It costs money, but more importantly, it is a threat to the safety of our patients. It impacts our ability to take good care of our patients. And we are reaching a point where it's becoming increasingly difficult to treat infections with these drug-resistant organisms.

There's been I think a growing awareness of this problem and a really a growing impetus to act on the problem of antibiotic resistance, and that's been something that we've seen slowly growing over the past several years. And a lot of that culminated most recently last fall and earlier this year with the release of both the national strategy and national action plan here in the United States for combating antibiotic-resistant bacteria.

This is a call from the Obama administration from the White House for a nationally coordinated effort to address antibiotic resistance throughout both the healthcare continuum and in agricultural settings. It represents I think the most ambitious and cohesive attempt to try and tackle this problem. We think that this is a critical opportunity to try and address this, and we have this action plan, which I think will help us do that.

One of the key components that we are addressing as part of our new efforts to combat antibiotic resistance was something that was summarized very recently in a Vital Signs publication from CDC. If you haven't seen the Vital Signs publication, these are a series that CDC does. There's a different topic every month, and healthcare-associated infections have been an important part of this effort.

If you search for Vital Signs, you'll be able to see all of the information that we released earlier this month. But what we showed in this Vital Signs report is through the use of modeling data, we were able to show the incredible impact that a coordinate approach has and the vastly improved impact that a coordinated approach can have over individual efforts to combat antibiotic resistance.

We know that the best way to address the problem of resistance it to have all of the healthcare facilities in a
given region working collaboratively, working with public health officials to address this in a coordinated
fashion. But we know that that approach is forward looking. This is an infrastructure and a capacity that we
have to build throughout the country at the local, at the state level.

We know what to do but we know we have a little bit of a ways to go to get there. And we know that it's going to take additional resources. The White House has asked Congress to make an investment in helping us combat antibiotic-resistant bacteria, and we certainly hope that Congress will take up that call and will allocate the necessary resources to get this done.

But I think it's important to emphasize that even though we have a lot that needs to be done and there's an infrastructure that has to be built in the future to take advantage and implement this type of coordinated approach, there's a lot that we can do today.

So this isn't something where we need to say well there's nothing we can do now, we just need to wait a future state where we can take this coordinated approach. We know that there are a lot of actions that we can take today that can be very effective. And both (Bob) and (Sara) are going to talk a little bit about some of these things that we can today and summarize for you what they've found in some of their work and then we'll have some time for questions.

And so with that, let me turn to over (Robert Weinstein). (Bob)?

Robert Weinstein:
Thanks, Arjun. I've been asked to talk today about the Chicago experience with the regional spread and control, particularly control of Carbapenem-resistant Enterobacteriaceae. We know a lot about the epidemiology of antibiotic resistance, and on that epidemiology are based our control measures.

So, on this slide you can see the resistance iceberg, which has been described more than 30 years ago. We know that the iceberg represents two to ten colonized patients for every clinically-infected patient. And on the right side, you see intra-facility spread, which has been our major focus over the years. And now on the left side you see that we're drawing attention again to regional spread.

This is not a new problem. Regional spread has been a source of antibiotic-resistant bacteria for years. This is an example of the initial emergence of multi drug resistant ESBL-producing Klebsiella and E. coli in Chicago, which was traced and related to nursing homes which appeared to be the major reservoir of those bugs.

And now with the emergence of Carbapenem-resistant Enterobacteriaceae, and on this slide you can see the worldwide distribution of Klebsiella and pneumoniae that are Carbapenem-based producing. And those KPCs are the most common form of CRE in the United States, and so you'll see some of my slides will say CRE and some will say KPC, because it is - represents the vast majority of CRE here.

With the global emergence of KPC, we've drawn new attention again, redrawn attention to the regional spread of antibiotic resistance. And I thought I'd show you our experience in Chicago with regional spread and with attempting to control regional spread.

So on this slide you see the initial patient with Carbapenem-resistant Enterobacteriaceae, a KPC, seen at Rush, was traced ultimately back to a long-term acute care hospital in Northwest Indiana. And when the dust settled, there were 42 colonized, mostly infected patients that were traced to this network of transmission.

And when (Sarah) looked, she observed extensive transfer of KPC-positive patients throughout the network depicted here, including 14 acute care hospitals, two long-term acute care hospitals, and ten nursing homes. So this called our attention to long-term care, particularly long-term acute care hospitals, or LTACHs as I'll refer to them, as a potential epicenter for KPC in our area.

So (Mike Lin) did a survey to assess the importance of LTACHs in the regional epidemiology of KPC. And what he did was a point prevalent survey of 25 ICUs. Every hospital in the city of Chicago that had ten or more ICU beds, and there's about 25 of those hospitals, and seven LTACHs in this general region were surveyed.

And you can see that 30% of LTACH patients were colonized with KPC compared to only 3.3% of ICU patients. So there was a ninefold higher colonization rate of - with KPC and LTACH patients. So we thought we had to intervene in the LTACHs and intervene regionally since this was not a problem at a single LTAC, and the hypothesis was patients were moving from LTACHs to nursing homes to acute care hospitals, and the LTACHs were the reservoir and the epicenter of KPCs in our area.

So to develop our intervention, (CJ Thurlow) looked at the epidemiology of KPCs in LTACHs. And our hypothesis was that like other multi-drug resistant organisms that we've studied, Vancomycin resistant and Enterococci, other gram negatives, MRSA, that patients who are colonized on mucosal surfaces, particularly the GI tract, tend to become colonized on the skin with the same organisms. So they're like microbiologic chameleons or they develop what I prefer to call a fecal patina or a fecal veneer of these resistant organisms.

So the first question we had was does KPC do that on the skin and is it like other bugs like VRE and Clostridium difficile, also a big environmental concern, where should we focus our efforts. And you can see on the slide (CJ Thurlow)'s findings. Ninety-two percent of patients that were studied who had KPC in their gut had more than one or more skin site, and half of the skin sites we cultured had KPC on them. And we're not talking about just perirectal or groin areas, we're talking about the axilla, the backs, areas removed the GI tract.

Interestingly, unlike other multi-drug resistant organisms that we studied, we did not find that environmental sites were important in the local epidemiology of KPC in the LTACHs that we studied. So based on this epidemiology, (Mary Hayden) at Rush led an intervention to try to control colonization by KPC in long-term acute care hospitals, and we focused on the four hospitals in our immediate area, the four LTACHs in our immediate area.

And you can see in the figure that there was a staggered introduction of our intervention. So every two months or so, a new LTACH was added, and this was a way of both marshalling our resources and also providing concurrent controls.

And the strikings were pretty - the findings were pretty striking. If you look at the intervention bundle, we did admission and every other week rectal culture screen of all LTACH patients in those four LTACHs. For those patients who were KPC positive, there was contact precautions in either cohort nursing or private rooms.

All patients -- all patients -- received daily bathing with Chlorhexidine-impregnated cloth so that every patient in the ICU in the LTACH every day got a bath with a Chlorhexidine-impregnated cloth that was a non-rinse Chlorhexidine application, and then we did education of healthcare workers and did some adherence monitoring.

And you can see at the top of the slide is the prevalence of KPC-producing Enterobacteriaceae rectal colonization. You can see there's about a year baseline in which the rates in these four LTACH was about 45% in point prevalent surveys.

With the intervention, you can see that rate fell from about the 50% rate to a little bit over 30% despite the continued introduction -- and that’s the bottom straight line with the triangles -- those are admission-positive patients. So patients continued to bring in KPC on a regular basis at a 20% rate. So 20% of the people walking in the door who are patients at these LTACHs were KPC positive. So we were able to bring down the point prevalence despite the continued reintroduction of these strains.

And even more striking is the lower right-hand figure which is the incidence rate of KPC-producing Enterobacteriaceae rectal colonization, which showed that we had more than a 50% reduction in the incidents. That is in new colonization events. Just as dramatic was the clinical impact. And these are (Mary Hayden)'s findings of our pre-intervention versus intervention effects of our bundled approach to preventing clinical infections at these four LTACHs. And you can see whether we look at the rate of KPC in any clinical culture, the rate of KPC bloodstream infections, which have a very high mortality, or bloodstream infections due to any pathogen, there were dramatic and statistically- significant drops in infection rates. So we thought this was an exceedingly effective intervention at these four LTACHs.

So the next question was if we're doing this intervention not only to help these patients in the LTACHs but to improve the regional epidemiology of KPC, have we done that. So we assessed this in two ways. First is this is a slide from (Mike Lin), who was heading our REALM project. REALM stands for regional evaluation of a legislative mandate to screen patients for MRSA.

So after the state of Illinois mandated MRSA screening for hospital - at high risk hospital admissions, we developed a group of hospitals that we followed regularly every six months, culturing patients for MRSA in their ICUs. When KPC emerged in our area, we grafted onto the REALM project KPC surveillance.

So basically every hospital in the city that had ten or more ICU beds, every ICU patient was cultured every six months and we had 100% participation, and in red you can see the LTACHs, so both the Chicago, the four Chicago LTACHs and three LTACHs that are outside the Chicago area but within the Chicago-land area.

And so we were screening these institutions, all of their patients, the ICU patients and the hospitals and all the LTACH patients every six months. And you can see our survey results from 2010 to 2014. The LTACH in light blue, prevalence, point prevalence of KPC colonization, fell in half, which is good. It’s what we observed in our bundled intervention. And there was no increase in adult ICU KPC infections. They stayed statistically at a similar rate.

So we think that we controlled LTACH transmission and that that prevented the emergence in ICUs in the city. But since this is point prevalence data and not continuous data, we thought that we really needed to have a more rigorous in time, real-time surveillance system.

And so what (Mike Lin) and (Bill Trick) developed with the Illinois Department of Public Health is what we call an XDRO, or extremely drug resistant organism registry. So the Illinois Department of Public Health made

CRE reporting mandatory, and it has to be reported through an online registry that was developed by (Mike Lin), (Bill Trick), and our colleagues at the Illinois Department of Public Health. And you can go to this www.xdro.org and look at the registry.

Basically how the registry works is shown on the next slide. The cases have to - all CRE-identified patients have to be reported by providers at labs of this registry. The registry is maintained electronically. Acute care hospitals, nursing homes, long-term care facilities can query the XDRO registry, and so when a patient is admitted to your hospital, you can query the registry to see if that patient's known to carry CRE and then place the patient on isolation precautions.

We are doing two things currently to simplify or facilitate this reporting. One is to develop electronic transmission from laboratories to make it easier for infection preventionists, and the other is we have an initial group of hospitals that are testing automated alerts so that when a patient is admitted to their hospital, their hospital electronically and automatically in the background queries the XDRO registry and the infection preventionist is a sent a note, an e-mail, saying that a patient that was CRE positive has been admitted. And so
the patient - the hospital is alerted in that way, and it's pretty dramatic for those hospitals that are part of the initial study.

So what are the results of our registry? This slide shows the unique CRE-infected patients reported to the statewide registry in the first 17 months. And you can see I suppose if you're an optimist a downward trend, but in any event, it's not an upward trend, and so we're going to be able to track the rates. And we know where these cases are being reported and it will help us develop a better view of clusters and of the impact of our intervention that occurred and is continuing in long-term acute hospitals, LTACHs, on the overall
epidemiology.

So let me summarize. We developed KPC and CRE control measures based on the epidemiology. Traditional control measures work. It turns out that the KPC has a fecal patina like other resistant bugs that we've studied, and controlling this fecal patina along with traditional either cohort or single-room isolation controlled spread.

By controlling spread, we also prevented infections dramatically. But the spread of resistant bacteria, and in this case, KPC, is common throughout our region, so controls must be applied regionally and beyond. And Arjun showed the cartoon figure showing the hospitals and public health. It really is a collaborative effort of public health, academic medicine, community hospitals, LTACHs, nursing homes, have to work together for control.

Once you develop interventions, you'll want to know whether they're working, and so you have to track resistance. And resistance has to be tracked regionally and beyond. Our approach has been citywide culture surveys, the REALM project every six months, and now development of a statewide XDRO registry, which is going to allow us to look prospectively at potential clusters and to understand the molecular epidemiology and the spread of CRE in a much better way. Thank you very much.

At this point we have a question for you. If you'd click on the box that best responds to your situation. And the question is: Does your facility currently have a mechanism in place to share information on resistant organisms with other facilities in your area? More than does it have a mechanism, is it a mechanism that's used.

So if you're sending someone from your hospital to a nursing home, do you have a formal mechanism, is it an informal mechanism, or there's no mechanism for sharing information about colonization. While you're filling this out I'll give you an anecdote.

One of the IPs who's participating in our initial trial of automated alerts sent a note to (Bill Trick) and (Mike Lin) saying that she had just gotten an alert that she had a CRE admission. The patient had come from a nursing home. She looked at the nursing home record. There was no note at all in the nursing home record that this patient had CRE. The nursing home may not even have realized it. And if it hadn't been for this alerting mechanism from our XDRO registry, she really wouldn't have known. And she said, "This is really, really, really cool."

I'll turn it back to you, Arjun.

Arjun Srinivasan:
That's great, (Bob). Thank you very much. And I think we're seeing from the poll it looks like -- it went away – but it looks like about half of the folks had at least some sort of - there we go, about half of the folks have some informal way of sharing information with other healthcare facilities. And that's always good. There's types of networks and friendships that you establish, and relationships to other facilities.

Interesting to see that looks like about a quarter of you, or maybe one out of five, have some sort of a formal mechanism. So that's also incredibly encouraging. And just 22%, around 20% of you, don't have any mechanism at all. So I think I am encouraged by that. It looks like three-fourths of us have some way that we're sharing information with other facilities in the area, and I think that's good. It's that type of information sharing that's going to be so important.

And for those of you who answered no here, I hope after this call you'll take the opportunity to perhaps talk amongst yourselves and see how you might be able to think about establishing some of these connections either informally through your local infection prevention or quality improvement network, or perhaps even something more formally in collaboration with your state or local health departments, so plenty of opportunities there.

So why don't we go back to the slides and now let me turn it over to (Sara Cosgrove). Dr. (Weinstein) gave a very nice talk about some of the - on the infection control side, so the things we can do to prevent the spread of resistant organisms, and we know the other side of the coin where we have influence is of course trying to prevent the development of these resistant organisms through improving our use of antibiotics, and (Sara)'s going to say a few words about that. (Sara)?

Sara Cosgrove:
Thanks, Arjun. I'm happy to be able to talk about my favorite topic today, even though I'm sending the slides in the wrong direction. So bear with me. So just a brief outline, because this is a pretty short presentation.

I'm going to convince any doubters in the audience -- and I hope we don’t have doubters -- of the importance of antibiotic stewardship,speak a little bit about implementation of stewardship in a single facility, again a little bit about antibiotic stewardship interventions to decrease C. difficile infection, and then give a really nice example -- I wish it were my own example -- but an example from another city about how a stewardship intervention worked across multiple healthcare facilities.

So why does antibiotic stewardship matter? I think it's important to recognize that when we talk about antibiotic stewardship, we are not talking about getting to a point where we don't use any antibiotics. We're really talking about getting to a point where we use antibiotics in the best possible way.

So the goals of people performing stewardship is not to, you know, get us to the point where we aren’t using antibiotics, because we all recognize that antibiotics have been an unbelievable force in modern medicine. They've saved countless lives and, you know, really transformed modern medicine. But we can't view antibiotics as just being a placebo. They do have side effects and they have side effects for both the patient that receives antibiotics as well as for the greater public health in the form largely of antibiotic resistance.

So we certainly see resistance increasing. We see lots of slides showing us that resistance continues to increase in our country and across the world. But when an individual patient takes an antibiotic, they have the risk of developing resistance in their own bodies and they can go onto develop infections with those resistant organisms. So there are two layers.

We also know that about 5% of hospitalized patients experience an adverse reaction when they are treated with antibiotics. Traditionally I think we think of people getting rashes on antibiotics but there's certainly numerous episodes of nephrotoxicity in a hospital at any time because of antibiotic administration, and of course C. difficile infection, which has really emerged in the past decade as a very significant side effect of antibiotic therapy.

You've all heard that few new antibiotics are being developed. The situation isn't as bad as it was five years ago. There are actually some interesting agents in the pipeline, but as those come forth, we have to use them properly
and really be thoughtful about how we use them, because we went to preserve them as long as possible.

And unfortunately even those these issues exist, in study after study, about 30%, and often more, of antibiotics that are assessed in the hospital, are found to be the wrong antibiotic or not even needed at all. So this is a critical issue.

If you don't believe anything I just said, I think it's also worthwhile to note, as Arjun mentioned previously, that the president of the United States actually thinks antibiotic stewardship is important. So if you need that kind of
validation of the concern of stewardship, I just reproduce here the executive order that actually has a full section about improved antibiotic stewardship, which for those of us who have been doing stewardship for a while was really a very exciting thing to see in this executive order.

If you're starting a program or would like to evaluate your program that you have now, I would direct you to this document that's been produced by the CDC called the Core Elements of Hospital Antibiotic Stewardship
Programs. This is a fantastic document that really lays out in a concise way what you should be thinking about when you think about starting an antibiotic stewardship program. And I would strongly encourage a visit to the website to download this. Print it out, read it, highlight it, and really see what's going on at your own institution.

I want to bring up a specific part of the recommendations that are in that document that's around implementation. And in stewardship, I think sometimes when we think of implementation we think of well what kind of interventions are we going to implement to improve antibiotic use, and that's very important and I'll speak about that in just a few slides. But before we think about that, it's very important to think about how to implement a stewardship program, so the program itself, to be a valuable resource to the institution.

And one of the critical issues about this, and I bring this up because we expect, you know, that we will see a result of President Obama's executive order and that we will in the near future probably have more requirements
that hospitals have stewardship programs. So it's very important that we think about how these programs should be implemented moving forward, particularly in hospitals that have not had a longstanding stewardship program.

So what's the most important thing? The most important thing is that the hospital leadership supports the program, and that support comes in many forms. It should certainly come in financial form. These cannot be
unfunded mandates. They won't go very far if they're unfunded. But also this needs to be intellectual support. So, you know, in the optimal scenario the leadership of the hospital will make a public declaration that the hospital cares about stewardship, that the goals of stewardship are important to the hospital.

And a secondary component of that is a willingness of the hospital administration to hold prescribers accountable for following the policies of the hospitals regarding antibiotic prescribing. So if you are at the point of starting a program or if you're evaluating a program, this should be a critical component of it. The hospital should be backing up the stewardship program.

And then of course there's also critical issues in deciding whose going lead the program. I think the most critical part of who's going to lead the actual program, the activities of the program, is someone with strong leadership skills. Stewardship concepts are often new to clinicians and hospitals and so really having a strong leader is going to be a critical component of making stewardship activities come to life. And then of course the administration should also be helping get access to antibiotic use data.

So this is important. So before you leap off into what are we going to do, what our interventions, you want to have this strong, stable, structure in place. And so when we talk about specific interventions, those hold many forms and really should be tailored to the needs of the individual site, but can include development of guidelines, targeted interventions, and of course as much as you can feed back what you're learning to prescribers as possible will be proportional to how much your prescribers change their practice.

So next I want to just give the example of interventions to reduce C. difficile infection. There are many stewardship interventions that have been described in the literature, but if you're specifically thinking of using stewardship to reduce C. difficile infection, I just have some advice about that.

So first I think we have to recognize that all antibiotics can cause C. diff, so that, you know, interventions that address broad spectrum antibiotic use in general may at the same time have an impact on C. difficile infection
rates. However there's a certain core group of antibiotics that can be a bigger problem. And classically those are clindamycin, second and third generation cephalosporins, quinolones andcarbapenems. And in addition to exposure to these agents, the duration of time that you're exposed to these agents is also a risk factor for development of. So when we think about interventions to specifically address C. diff, you want to be thinking about those agents and you want to be thinking a how can we get the duration shorter of those agents.

So if this is an issue that you would to address in your institution, I think it's important to think about where these agents are used in your institution, and I put some examples here, because I think we see Clindamycin and second generation cephalosporins used as surgical prophylaxis, certainly cephalosporins and quinolones are common agents used to treat community-acquired pneumonia, and the same agents are commonly used to treat urinary tract infections, and unfortunately are commonly used to treat asymptomatic bacteriuria, which should not be treated at all.

And then carbapenems I think are a unique class of antibiotics, where you can take a look at the epidemiology of gram-negative resistance in your institution, and if you don't have a lot of that, then you may not need to be using as many carbapenems as you are. So that is also hospital specific, the degree to which you need to be using carbapenems that can sometimes be a nice target.

And so as I mentioned, anything you can do to get people to use fewer of these drugs for a shorter period of time has the potential to make a difference in C. difficile rates. So if you can get people to not treat asymptomatic bacteruria, so don't even start therapy in the first place.

For patients with CAP, if you can get them to narrow away from quinolones or third generation cephalosporins. If you can use published recommendations of durations of therapies for UTI and CAP that sometimes haven't
made it out to the general prescribing audience, you can get those durations in your hospital to be shorter. And of course use standard recommendations for surgical prophylaxis that those agents be stopped ideally at the time the patient leaves the operating room but for no more than 24 hours after.

Some other considerations with C. diff, because treatment of C. diff really involves the whole hospital, it's important that you not just say well our goal is to reduce ceftriaxone and we'll just replace that use with something else, because as we said all antibiotics can cause C. difficile. So really your goal should be overall use of agents, not just substitution of one agent for another.

Something that we often don't think of in infectious diseases is the association between proton pump inhibitors, which sometimes it seems that every patient in the hospital is receiving, and C. difficile, but in fact those agents are associated with a significant increase risk of C. difficile infection. And as stewardship teams are assessing antibiotic use, they may want to take a look at proton pump use at the individual patient level as they make recommendations.

More and more, we're understanding the impact of over-testing for C. difficile infection on our institutional C. diff rates. So anytime you're using a PCR-based testing approach, you're not only detecting true C. difficile infection but also colonization, and patients with colonization don't need to be treated for C. diff; however, they do contribute to your C. difficile infection rate.

We know that probably about 20% or even more in some series of hospitalized patients are colonized with C. diff and their tests will be positive if you send them. So even though not all hospital-acquired diarrhea is due to
C. diff, if they - your patient has diarrhea from being given laxatives, if your patient has diarrhea from being given tube feeds and they're colonized, their tests will be positive. So some stewardship groups have focused on really addressing C. difficile testing as a way to reduce C. difficile rates.

And then finally I know we have a lot of folks involved in infection prevention on the phone, and I cannot possibly underestimate the importance of infection control in reduction of C. difficile rates at the same time that you're thinking about improving antibiotic use. And this is really a lovely collaborative opportunity for stewardship programs and infection control programs to work together towards this common end.

I just wanted to give you an example from a country that is not the United States. Of course Scotland is much smaller than the United States, but they did decide as a country to make efforts to reduce C. difficile infection. They started stewardship programs in all of their hospitals in 2008. The focus was reduction in the use of fluoroquinolones and third generation cephalosporins, and they saw a very nice decrease, as you can see from the green line, during the period of this intervention in C. difficile infection rates.

In addition, they also saw decreases in resistance to these agents. So they saw decreases in resistance of third generation cephalosporins and E. coli, and they saw decreases in resistance to fluoroquinolones and pseudomonas. So this was a two for the price of one intervention. And at the same time they noted no statistically significant increases in resistance to other antibiotics, implying that they really successfully decreased overall use.

So this was not a substitution of quinolones and third generation cephalosporins for some other class of antibiotics. They really successfully got patients - got prescribers to use fewer antibiotics.

Now finally because we are not Scotland, we are much bigger than Scotland and more complex than Scotland, I just wanted to finish describing a multi-center intervention to improve antibiotic use that was in the United States. This occurred in Rochester, New York. And these slides were provided to me by (Libby Dodds-Ashley), who was the pharmacist who was part of the group that led this program. So I want to give her recognition and thanks for this.

So I'm describing the Rochester C. difficile infection prevention collaborative. This was a collaborative among four - the four hospitals in Rochester, New York. They had just modest funding from a local third party payer as
well as the hospitals that were involved. It paid for a little bit of physician time, a little bit of pharmacist time, and a little bit of data analyst time. And I think that this is a great example of how a collaboration that doesn't cost lots of money can actually drive change across a city, and I think it's fairly remarkable.

They particularly wanted to focus on interventions to reduce C. difficile infection. There was another arm ofthis work that focused on the infection control intervention to reduce C. difficile also, but it was actually when
both things happened at the same time where they really saw more of a difference.

They started with a point prevalent survey about UTIs. So they looked at all four hospitals and they discovered that 20% of patients who were receiving antibiotics for urinary tract infection had no symptoms. So lots of
treatment for asymptomatic bacteriuria. And they found that 86% of patients receiving antibiotics for UTI did not meet criteria for treatment. So significant issues surrounding urinary tract infection, and if you think about what drugs are used to treat these in your hospital, it's usually cephalosporins and quinolones.

So they recognized they needed to do something, and one of the first steps they took was to make this document that you can see on the slide. They basically took the logos of the four involved hospitals and put them up on the top of the document, made a box that showed this alarming information, and made a set of recommendations.

This was actually - (Libby) made this document kind of at her desk one day but it looked very official, and people took it officially. And so I think it's a fantastic example of how you can really drive change with an official looking memo and a group of people that really want to see change, because they did see a remarkable uptake in the recommendations to not treat asymptomatic bacteriuria.

And then finally, another intervention that this group made was a CAP treatment intervention. Their goal was to avoid fluoroquinolones as much as possible because of the association with C. difficile. And so they said well what can we use instead of fluoroquinolones and came up with the idea of using ceftriaxone and doxycycline. They chose doxycycline as the agent to cover atypical because of some data that suggests that doxycycline could actually be protective against C. difficile infection.

And so this again was a document that they developed, encouraged the participating hospitals to use these recommendations, and this is to some degree happening in somewhat real time. So they do have some results. In summary, they saw their desired reduction in antibiotic use and C. difficile infection, but the official results are going to be presented at ID Week, so I would encourage everyone who is thinking about going to ID Week to get some more information about these projects.

And so with that, I will finish up because we have covered the entire spectrum of antibiotic stewardship in a very short time. And I think we do have an ask-the-audience question. Does your facility currently have a stewardship program in place that implements the CDC core elements?

I think everyone can read that for themselves because you're already answering. So, Arjun, shall I turn it back to you?

Arjun Srinivasan:
Yes absolutely. So we'll let folks - we'll give folks just a few seconds to answer this polling question and then we'll turn it over to Q&A.

While folks are answering this question, let me ask if the operator can remind folks, or (Ibad) if you want to remind folks, how they can ask a question either via the phone or via the chat feature in the webinar. Would you
mind reminding folks about how they can ask questions?

Ibad Khan:
Thank you, Dr. Srinivasan, and thank you for the presenters for providing our COCA audience with such a wealth of information. We will now open up the lines for question-and-answer session. When asking a question, please state your organization and remember you can submit questions through the webinar system as well.

(Kathy), please open the line for questions.

Coordinator:
All right. And once again to ask a question, please press the star 1 and please record your name. One moment please.

Arjun Srinivasan:
And while (Kathy)'s grabbing some questions for us, I'll just summarize it's very encouraging again here. It's nice to see about 28% of folks have all the core elements implemented and that's great. So those are stewardship programs that are probably more mature, and these are the places where we'll be looking for, for innovations for driving what's next in stewardship.

We've got some of you who have implemented some and hopefully are working towards implementing others. And a really small percentage of folks who haven't yet started. So I think encouraging trend at least to see that people are beginning to implement the core elements.

And so let me see if (Kathy) has any question for us on the audio, and I'm going to take a look at the Q&A as well. I don't see any questions in the chat feature as yet, so let's see if there are any questions on the phone line. (Kathy)?

Coordinator:
Our first question comes from (Vivian Dangio).

Vivian Dangio:
Yes. I was a patient. I had a tooth extracted and was given clindamycin. And about a month later was very ill following four months with C. difficile. And my question is are you alerting dentists and dental surgeons to the information you're sharing with doctors?

Arjun Srinivasan:
This is Arjun. Absolutely. We recognize that, the dental community is a key group that we need to reach. We are in the process now of finding the best ways to engage them. I will note that the American Dental Association participated in the recent - well in June, we had a forum at the White House hosted by the White House on antibiotic stewardship, ways that we can improve antibiotic use in both human and animal health.

And the American Dental Association was there represented and came forward and said that they are eager to work with all of us to try and make sure that dentists get the same messages on improving antibiotic use that we're trying to get to all other healthcare providers. And thank you for raising that point because it is an area sometimes that gets overlooked. Other questions?

Coordinator:
Our next question comes from (Fred Penover).

Fred Tenover:
Hi this is (Fred Tenover) from (Southead). (Bob), it seems like you've made the assumption that people with CRE are colonized for life, and I wonder if that means we're ultimately going to put a lot of people into isolation that don't need to be there. Did you consider doing follow-up screening?

Because I know for MRSA at Baltimore, (David Hooper) and colleagues looked at follow-up cultures to get people out of isolation and saved a significant amount of money. So could you comment on rescreening patients once they've been given the label of CRE?

Robert Weinstein:
Yes that's an important question and it is - definitely impacts the question of our XDRO registry and how long you stay in there. So far the information we have, and other have published also on this, is that colonization with CRE in a sizeable proportion of people, in, you know, 20, 30% or more, is months and months, and I think maybe years or more.

And even in people for whom you can't find the organism with a routine culture, if they're re-exposed to antibiotics, they may - the resistance may reemerge. So there are a couple practical implications. As you said,
(Fred), one is retesting, and I would think it would be when the patient's been off antibiotics for some period of time. I can't give you the precise number of weeks or months, but I think it's more months than weeks -- more months than weeks if you want to retest them.

The second is what do you do when they reenter a facility. I think if they come into a facility, that's a time when you can retest them, put them on isolation and re-culture them and see if they're positive or not. That would be a cue to retest them.

And the third is for those people who are persistently positive, is there anything that can be done. And as you know, people are looking at altering the microbiome or trying to replace the microbiome of patients with resistant gut flora with healthy microbiomes such as done for treatment of clostridium difficile recurrence with fecal transplants. And so that's an area of active investigation that's still a research question.

So I guess to summarize, one, I think people do remain positive for months rather weeks. Two, culture them – you can re-culture them when they come back to a facility while they're on isolation and see if you need to maintain isolation. And three, stay tuned to the research outcomes from trying to adjust microbiomes.

Fred Tenover:
Okay thank you very much.

Arjun Srinivasan:
That's great. Thank you. And let me - while we're loading up more questions from the audio, there's a question here from (Andrea McClure) who wanted to know what role the clinical laboratory plays in an antibiotic stewardship program. And, (Sara), I wonder if you might say a few words about that.

Sara Cosgrove:
The clinical laboratory is kind of critical in most stewardship programs. And we recognize that there are hospitals that don't have access to a microbiology lab onsite, and that can be a challenge. But whatever can be done to reach out to the places that are doing the microbiology can certainly benefit that stewardship program.

If you're fortunate to have a microbiology lab onsite, I think that there are a wide range of collaborative interventions that can be developed starting on one end of the spectrum with deciding, you know, are there
antibiotics that you don't want to report for certain bugs or bugs and sites so as to try to gently steer prescribers into prescribing the narrower antibiotic choices.

It's critical to work with the microbiology lab to develop annual antibiograms so you get a sense of resistance trends in the institution which can help with deciding what kind of empiric antibiotic recommendations should
be made.

And then now that we are seeing the rapid evolution of the availability of rapid diagnostic testing, the micro stewardship collaboration becomes even more important because micro labs spend a lot of money on implementation of these tests and consequently would like clinicians to use them when they treat patients. It's a shame to do a bunch of testing and then not actually have it used in the care of patients.

So stewardship teams can really form the bridge between the micro lab and the treating clinician with assistance in interpreting the results of those tests and guiding antibiotic decisions based on the results of those rapid diagnostic tests. And we see more and more of these, I think that role of stewardship become more and more important.

Arjun Srinivasan:
Great thank you, (Sara). (Kathy), are there any more questions on the phone line?

Coordinator:
Yes we have a question from Maryland Department of Mental Health and Hygiene.

Maryland Department of Mental Health and Hygiene:
Thanks to both the speakers for a great presentation. You both mentioned skilled nursing facilities, and you can elaborate a little bit more on the role that interventions and work in skilled nursing facilities plays in these efforts? And in particular whether and if so how interventions in skilled nursing facilities are similar or different from acute care and LTAC settings?

Arjun Srinivasan:
(Bob), do you want to take that one?

Robert Weinstein:
Sure. That's an important question. First there are different types of nursing facilities. There are, depending on the needs of the residents, there are some that are more domiciliary, there are some where patients are on ventilators, and there are some that are long-term acute care hospitals.

And as you go from a domiciliary to the vent SNF to the LTACs, I think the risks of the patients and the risks of MDROs increase. And I think the interventions need to be ramped up. So I think you need, like infection control anywhere else, education, you need to understand the epidemiology of what's going on, and you need to develop interventions based on that epidemiology.

I think that because of the heavy turnover of personnel, at least in the long-term facilities that we've worked with, I think it's - there has to be a strong emphasis on education because there's turnover of personnel, new people are there, and you need to reeducate, reeducate, reeducate.

So I think it's, one, understand the epidemiology, understand the rates of resistant bugs or problems in that facility and develop interventions based on the epidemiology of those bags, and do these interventions as stressed here in a regional way, not just for a single facility. Because of the movement back and forth between hospitals, LTACs and SNFs, you can't just have work at one place. So I think it's important to develop a cohort of infection preventionists who know each other in these facilities and will work together and can share best practices.

(Sara) might want to comment on antimicrobial stewardship. I know in the one long-term care facility that we oversaw for a number of years, which had 600 and some beds, relatively stewardship interventions by (David Schwartz) were able to bring down antibiotic use by about 50%, and that was - with that, there was a major drop in antibiotic resistance in the facility. So I think antibiotic stewardship is very important, particularly related to non-treating asymptomatic bacteriuria, which I think (Sara) emphasized appropriately.

Sara Cosgrove:
Yes I agree completely, (Bob). I think that the first step in any of the non-acute care settings, including long- term acute care settings but not an acute care hospital, is seeing if anyone is looking at stewardship opportunities. And so that's really the first step.

There have been many approaches that have been described in the literature, and as you mentioned, largely directed at non-treatment of asymptomatic bacteriuria, particularly in the long-term care environment. You know, skilled vent facilities and places with much more acute patient populations, that antibiotic use can often look a lot like that of an acute care hospital.

But again, assessing what resources you have and remembering that it's really the leadership skills of the person who's going to start the stewardship program that makes a huge a difference. So even if they've never done
infectious disease before but have some passion and leadership skills that can go a long way to building consensus about change in approaches to antibiotic use.

Robert Weinstein:
Does that answer the question for the questioner?

Maryland Department of Mental Health and Hygiene:
Thank you.

Arjun Srinivasan:
Well it's now a little bit past 3 o'clock. I want to thank everyone for sticking with us and for joining us and giving it an hour out of what I'm sure are very, very busy days. I learned a lot from this call. I hope you did as well.

I really want to thank (Bob) and (Sara) for just really outstanding presentations and helping with fielding – graciously taking time to field questions and answers. I thought this was a fantastic call.

These slides will be available, and let me turn it back over to (Abad) for some closing logistics and comments on the availability of the slides, the archive and (unintelligible) information. (Abad)?

Ibad Khan:
Thank you, Dr. Srinivasan. I also would like to thank everyone for joining us today with a special thank you to our presenters Dr. (Weinstein) and Dr. (Cosgrove). We invite you to communicate with our presenters after the
webinar.

If you have additional questions for today's presenters, please e-mail us at coca@cdc.gov . That address again is C-O-C-A@-C-D-C.G-O-V. Please put August 20 COCA Call in the subject line of your e-mail, and we will
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The recording of this call and transcript will be posted to the COCA website at emergency.cdc.gov/coca within the next few days. That web address is emergency.cdc.gov/coca.

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Coordinator:

Thank you. This completes today's conference. You may disconnect at this time.

END