Tackling an Invasive, Emerging, Multi-drug Resistant Yeast: Candida auris — What Healthcare Providers Need to Know

Moderator: Marcy Friedman

Presenters: Tom Chiller, MD, MPHTM

Date/Time: August 15, 2017, 2:00 – 3:00 pm ET

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>> At the conclusion of today’s session the participant will be able to explain the epidemiology of C. auris, describe the guidance for diagnosis and treatment of C. auris, and describe the infection control recommendations for containing C. auris. Today’s presenter is Dr. Tom Chiller. Dr. Chiller is an Infectious Disease Physician, who has specialized in fungal diseases for the past 20 years. He leads CDC’s efforts to combat fungal diseases as the Chief of the Mycotic Diseases Branch in the Office of Emerging Infectious Diseases in the National Center for Emerging and Zoonotic Infectious Diseases at CDC. He attended the Tulane School of Medicine and the Tulane School of Public Health and Tropical Medicine. At this time, please welcome Dr. Tom Chiller.

>> Thank you. It is certainly an honor and a pleasure to be here during our first inaugural Fungal Disease Awareness Week, and I look forward to talking to you a little bit about an emerging fungal pathogen that is really causing some consternation and challenges amongst the healthcare community. So generally, as you all know who work in healthcare and see infections, you know that most of the time the public thinks of fungal disease as what is shown in the picture here. So this is a classic, very advanced case of onychomycosis and clearly probably the most common clinical manifestation of fungal infections out there. But, thankfully, as bad as these fungal infections look they aren’t deadly and what we are obviously concerned about is deadly infections. So what healthcare professionals think about severe threats? Next? We are obviously worried a lot about bacteria and CDC has put out warnings about this bug, CRE, that many of you might have heard about, with resistance to many if not all available antibiotics in some cases. Next? We also hear a lot about this newest bacteria, multi-drug resistant Acinetobacter, and we’re very concerned about the problems with it. Next? And of course MRSA and the continuing problems we have with MRSA spreading in hospitals and even getting into communities and sports teams. Next? And then finally our friend, C. diff, which has really come on to the scene in healthcare settings and we’re really fighting C. diff in a lot of different ways, including even stool transplants and different ways of thinking about these things. Next? But now there’s a fungus among us. Next? And this fungus is pretty serious, in fact, fungi cause serious invasive infections, not just the toenail. Candidemia, which is the bloodstream manifestation of fungal infections due to Candia, turns out in recent studies that we’ve looked at are the most common if not some of the most common healthcare associated bloodstream infections in our country, in the United States. The incidence being somewhere around five to 15 per 100,000 and mortality ranging from 30% to 50%, and so these are very serious and sometimes deadly infections. Next slide? The risk factors for candid are sometimes we call in the fungal world the other C. diff, have somewhat similar characteristics in that broad spectrum antibacterial use is a very common association with those who develop infections due to Candida. And it makes some sense because we use broad spectrum antibiotics and tend to eliminate all the good and bad bacteria, if they exist, and what’s left, fungus. And since Candida is in our gastro technical tract we know that we select for a lot of Candida to remain in the host, and that’s why when you’re immunocompromised, you’ve been in an ICU for prolonged periods of time, you’ve had abdominal surgery where the Candida exists and they exist in a normal fashion, or you’ve had central lines, all of these things with the combination of broad spectrum antibiotic use, really raise the risk for these serious fungal infections. Next slide? As I mentioned, source of infections due to Candida generally we think, and from conventional wisdom, that these are really auto infections with our own host gut flora. Next? And transmission in hospital environments, therefore, is really not thought to be common at all. We do occasionally see outbreaks mainly with a species called Candida parapsilosis, but these outbreaks are actually very rare. Next? If you look here at about 7,000 isolates that we have from our surveillance system within the Emerging Infectious Program here at CDC with state and academic partners, you can see that this pie chart represents the different species that we see and the blue is the classic species of Candida albicans. If I would have shown you this same pie chart from about 20 years ago that blue would be much bigger, in fact, it would probably accompany both the blue and the orange. But you can see here now the orange, which is Candida glabrata, is a species that’s more and more common and the Candida parapsilosis, which is the gray, is now the third most common. And if you combine the non-albican species they actually now make-up the majority of the Candida that we see and, in fact, in some hospitals Candida glabrata is over 50% of the bloodstream isolates they see. Next slide? So why do we care about this obscure Candida species called Candida auris? It doesn’t even show up on that slide I just showed. Next? Well, let me give you a little background and a little history of this thing. It was named back in 2009, auris being Latin for ear, from a patient that had this new type of yeast isolated from an external ear canal, of a patient that they thought had an external otitis and, therefore, it got its name, Candida auris. Next slide? We then saw a pretty rapid emergence since that first report in 2009, but here we weren’t dealing with ears anymore, these were really mostly blood isolates. So, in effect, the candidemia that we worry about and we worry about causing severe infections. So if you look here, Japan where it first was reported, then South Korea, India, South Africa, Kenya, Kuwait, so now it’s in Africa, Pakistan, Venezuela, we now know Colombia, Israel and the United Kingdom, so really as you can see as you look at this map, pretty rapid emergence in a lot of places around the globe. Next slide? The other thing we learned about this bug that was particularly concerning was it’s the fact that it was multi-drug resistant in many settings. Next? So about 90% were resistant to the Azoles, the fluconazole, voriconazole, itraconazole, anti-fungals. Next? Around 30% or so were resistant to the polyenes, the polyene being amphotericin B, the drug that is still our go-to drug for obviously many infections. Next? And around 10% to 20%, depending on where we looked, were resistant to the echinocandins, the echinocandins being our recommended first line therapy for Candida bloodstream infections in this country. And a few of these isolates from the original 50 or so isolates that we collected from around the world were actually resistant to all three, and that was a first in Candida and that certainly raised some alarm bells with us and others who are studying and looking out for emerging pathogens and especially fungi. Next slide? Obviously, there was some healthy skepticism when we described this relatively rapid emergence of this multi-drug resistant yeast. Was actually this bug here with us all along and we just never identified it? These newer diagnostic methods that we now are using to be able to identify, MALDI-TOF and DNA sequencing that have come on the scene much more recently, was that the issue and we were just identifying something that had been there all along? Most systems misidentified this particular Candida auris actually as something called Candida haemulonii or sometimes they call it other species. Next slide? So we worked with colleagues around the world, looked back at our own collections, made sure that we re-sequenced any questionable isolates. And you can see here that looking at somewhere close to 40,000 isolates going back a couple decades there was absolutely no C. auris, and we didn’t find any C. auris as mentioned before that Japanese strain. We did hear of an isolate from South Korea. We’ve never actually gotten that isolate to verify it, but there was one recorded in South Korea in 1996, but that’s the only isolate before 2009 that we were aware of. Next slide? So how did this pathogen emerge? When we start thinking about it, looking at that timeline that you saw, we wondered, huh, something emerging that quickly in the fungal world there must be some global spread of some epidemic strain, it must be moving through some medical product or the food supply or something. Or could this have been many introductions from the environment or some other source? And we used whole genome sequencing, one of the newer tools we use now in epidemiology, so sequencing the entire genome of the organism to help us provide some pretty remarkable but puzzling results, which I’ll show you next. Next slide? You see here that we got a group of 47 isolates from four world regions and we saw using whole genome sequencing that these were dramatically different, really four distinct clades — South Asia, South Africa, East Asia and South America is what we were calling them based on their geographic location. But these were dramatically different, I mean we’re talking, when you talk in the language of whole genome sequencing we refer to SNPs, single nucleotide polymorphisms, and these were 40 to 400,000 SNPs difference, which is huge differences. Next? Whereas, when we looked within the regions they were almost identical. Next? I think it shows the number of SNPs, less than 70 SNPs in these clusters, some of them two or three SNPs difference, suggesting that there were indeed simultaneous or almost simultaneous emergence across four continents with incredibly clonal spread within those continents. Next slide? But then, so this was all the data we were collecting, but then this experience in the UK really got our attention. We heard of an outbreak in a UK hospital in London, they had nine Candida auris bloodstream infections, more than 40 people were colonized, and they were telling us that there was clear patient-to-patient transmission. Next slide? They also talked to us about how difficult this thing was to control. They were using contact precautions, they were screening people to see if they were colonized, they were doing chlorhexidine bathing and cleaning the room with bleach three times a day. They were doing terminal cleaning of these rooms with even a higher concentration of bleach used for regular cleaning. And they eventually actually closed an ICU, which is really unheard of for a Candida, certainly for a yeast. Candida was cultured from many hospital surfaces. You see the picture there of the hospital room, they cultured from the bed, the equipment, the sills, the windows, even the floor. Next slide? When we heard all that and we talked to our colleagues in the UK we realized we needed to put out an alert and let healthcare facilities, healthcare providers, the healthcare community know about what we were hearing. And so we put out this alert in June 2016. Next slide? And here is a couple months old but relatively new graph of the cases that were subsequently reported to us and the states where they are. And you can see here that after the alert came out we did identify one isolate that was back from 2013 and one from 2015, but most of them occurred around the same time that actually we had put the alert out, let laboratories know they could send us their isolates that were questionable, and we began working with states, especially like New York and New Jersey, where we began seeing quite a number of cases. The most recent and up-to-date information is on our website, but I can tell you that I know we are above 100 cases currently in the US. Next slide? And you can see, here’s a map and again as I mentioned the majority of cases reported so far are really occurring in New York and New Jersey, with a few spotted cases in different states that I’ll talk about in a moment. Next slide? So we got as much information as we could working with our state and local colleagues to understand what does the epidemiology of the cases in our country look like. Next? So 75% of these isolates were from blood, so they were candidemia. Next? Median age was 70. One case in a neonate. Multiple underlying medical conditions and indwelling devices, tracheostomies, central venous catheter, gastrostomy tubes. So these patients had extensive healthcare exposure, so they were really medically experienced patients. But they were in acute care hospitals, LTACHs, they were in SNFs A resistance pattern, 80% to fluconazole, so pretty consistent to what we were seeing, a little higher, 40% to Ampho B, which again is not something we like to see. And thankfully are only around 3% resistant to echinocandins, with no isolates to date having all three anti-fungal class resistance yet, which is great. The 30%, 30-day mortality was not an attributable mortality, it was all cause mortality, and as I said many of these patients had extensive healthcare exposures and were sick. Next? Four cases had recent travel. Next? Countries involved — India, Pakistan, South Africa, Venezuela, again, all on that map. These cases were interesting because they involved urine and wound cultures, occurred in Connecticut, Oklahoma, Indiana and Florida. Next? And when we tried to understand about how they could be linked back to these potential countries of origin, I bring you back to these four clades again. Next? And when we take a closer look at these four clades we see that the US case isolates are actually related to those from multiple parts of the world and they’re actually even closer and they’re also closely related within each state. So as we click through this. Next? You’ll see that the South Asia clade is very closely, tightly related to New York, New Jersey, Oklahoma, Connecticut and Maryland. Next? There’s also a New York, a few isolates that are very, very clonal with the East Asia clade. Next? In Illinois, Massachusetts and Florida they’re very similar and almost identical to the South America clade. And then, next, in Indiana, the Indiana isolate similar to that in South Africa. So here we go, we have all of the isolates that we know of and have been able to sequence to date clustered with one of the clades that has been identified in our original analysis, suggesting that these cases, these isolates, these infections that are occurring in the US are not from strains that have really come up from within the United States, but instead were brought over, but then have spread in some of those environments. Next slide? So you can see with recent emergence in the US, maybe the mid-2015, we’ve had multiple introductions of Candida auris, followed in some cases by local transmission. Next slide? So let’s talk about this transmission issue because I told you, if you remember back at the beginning of the talk, that really we think of Candida and candidemia as almost an auto-infection. You bring your own Candida species in with you to the hospital, you get exposed to lots of healthcare interventions, including broad spectrum antibacterials, and you select for Candida and then that Candida can get into your bloodstream through various mechanisms. Next? What we tried to understand more is about C. auris. And you heard I mentioned that in the UK setting they obviously were super concerned about healthcare transmission and certainly all the things they were doing were focusing more like this thing was a bacteria than a typical fungus. We know then we did some studies with them and with others that Candida auris really likes to colonize the skin and other body sites, and you can see here the axilla growing, nares, the ears and the oral cavity, we can find Candida auris readily in many of these parts of the skin. Next slide? And I already mentioned and showed this picture, a similar picture from the UK, we know we can also culture Candida from almost any part of this hospital room after a patient has been there and it manages to survive and contaminate the environment for weeks to months and we’re finding is very difficult to kill. Next slide? So here’s just a small study we did looking actually at a couple of patients that were in nursing homes. One had an ear culture, one had a central line tip, and one had blood, and we cultured the neighbors, so to speak, of these three patients. Next? And we actually found that some of them were colonized with, again, the identical strain that these patients had had who were in the same environment. Once again suggesting this isn’t something they just came in with on their gut, it’s something that actually may have been on their skin, left then onto equipment or had been moved by equipment or human-to-human contact and transmitted at least on the skin to other patients in their vicinity. Next slide? We also tried to understand transmissions more by culturing on different surfaces. And in our lab it persists easily for weeks on plastic surfaces, it grows very nicely. We’ve now seen skin colonized for months, I think up to nine months is our current understanding, but could be even more. And the quaternary ammonium compounds that we sort of use as the major disinfectant in our healthcare settings do not work to kill this fungus. Next slide? So really what we’re talking about here is a paradigm shift for your typical Candida infections and that’s why I try to talk to as many people as possible about this. Because I’m a fungal infectious disease Doctor and I’ve been treating and dealing with fungal infections for years, but this really was the first sort of fungal infection that actually to me was acting like a bacteria and I often call this the yeast that wants to be a bacteria. Anti-fungal resistance is the norm here, instead of the exception, which we often see with most of our fungal pathogens. It thrives on the skin, like other bacteria, it contaminates patient rooms and can stay there, and again different than what we typically think of Candida, it spreads in healthcare settings. Next slide? So how do we control the spread of C. auris? Well, it’s different than we, again, would think if I was telling you how do you control the spread of Candida albicans or how do you control Candida glabrata, some of the more common species that are causing bloodstream infections. We’re going to say you have to control this like you were controlling Acinetobacter or MRSA, you identify that it exists, you treat when it’s warranted, and then you get into the infection control mode, which again when someone says Candida infection control those things don’t generally go hand in hand and we’re trying to tell you that in this case they really do. Next slide? There have been some challenges with actually identifying this organism and it’s one of the reasons why after the alert and after working with local health departments and states and hospitals around the country and in educating and also even working with the companies that make a lot of these identification machines, to get this identification into current use in microbiology labs has been an ongoing effort by a lot of different folks. But you can see here and it’s in more detail on our website, as well, what Candida auris can be misidentified as. And, in fact, we’ve had clusters of Candida haemulonii that had been sent to us where they were concerned about Candida haemulonii and, indeed, these were all Candida auris. But there are some other less common things that we see and so it’s going to be really important to ask the question, how, what is our lab capable of, how are we identifying it, and if you need help reach out to your state, they can reach out to us. Next slide? About 30% of the clinical cases in the US have been actually from non-bloodstream isolates, urine, bile, wounds, et cetera. You know, these are non-sterile sites, oftentimes, and they don’t often get worked up to the species level. You’ll probably get a result, urine Candida. What’s going to be challenging and what we’re currently in the process of recommending is that because we are concerned about containment, because we are concerned about transmission even though there may be no treatment needed for these types of non-sterile fluid cultures, infection control is going to be needed if it’s Candida auris. Next slide? It’s also obviously challenging to detect those who are colonized, so if you had a patient in a facility and then were trying to do point prevalent survey, so we’re trying to survey around that patient to see who might be colonized, but I think we’ve had decent success now doing growing an axilla cultures, where we take one swab and we swab both axilla and both sides of the growing. And we’ve been doing a much better job at being able to find colonized individuals that way. One of the interesting things about Candida auris that we found in the lab is it likes to grow at slightly higher temperatures than other Candida and also likes to grow in a very high salt environment. So we’re able to sort of eliminate the other Candida very rapidly in a medium that has double the salt of the ocean, for example, and at 42 degrees instead of the normal body temperature of 37. So it’s interesting and it maybe makes some sense that axilla growing might be areas where this organism likes to hang out and is successful. Next slide? So, again, it’s important to know who is colonized because that’s when we’re going to put those infection control measures in place and we’re going to know how to do terminal cleanings around these patients and in these rooms. Next slide? I also want to mention a network of labs called the ARLN, which stands for Antimicrobial Resistance Laboratory Network. This is a new CDC initiative working with seven regional labs. You can see here each of these labs is representing this particular region. The goal of these labs is to provide some core testing for different bacteria and Candida, as well, to be able to monitor for resistance and provide some support. Again, these are not clinical labs, they’re not meant for clinical results to be communicated in a timely manner back to a hospital, but they are going to help tremendously in providing understanding and support certainly for identification of resistance and understanding hopefully where it is and picking things up early. So I wanted to just let you know about this program that is happening. Next slide? So what about treatment? Well, as you saw, only about 3% of the isolates we have seen in the US are resistant to echinocandins. Echinocandins are the first line therapy for this yeast and they continue to be. We obviously are watching carefully to see what resistance patterns develop. Clearly resistance can be very problematic and is very concerning when I think of the fact that some of these infections in other parts of the world have resistance to all three known anti-fungals and we’re going to really struggle when we get to that point of how to be able to treat those isolates. Again, I mentioned we have some echinocandin resistant isolates in this country and we know of at least one, but I’ve heard of multiple now cases where the echinocandin resistance actually developed while they were on echinocandin therapy and that’s again concerning and again something more typical of a bacteria. And so it’s going to be really important that we monitor patients while they’re on therapy if you do have a patient with Candida auris. Next? Again, infection control is the key for stopping transmission of this organism. Next? Handwashing, you know, the classic hand hygiene, incredibly important. Next? Obviously, contact precautions, gowning and gloving. And, finally, disinfection which is going to be really important in cleaning surfaces because this organism, as I mentioned, really likes to stick to things. Next slide? So standard and contact precautions, put patients into a single room, reinforce the hand hygiene. Again, these are all things I know you all know about just in general from infection control. One of the things that’s slightly different is that we’re recommending daily terminal cleaning with disinfectants with a clostridium difficile claim, so a sporicidal claim because again we’ve had some issues in seeing using the quaternary ammoniums that we’re not getting killing like we should be. And then, finally, contact tracing of known cases is something we have been engaged in with hospitals and states in these 100 cases or so that we’ve had in the United States so far. Next slide? One of the things that concerns us and concerns me definitely is sort of understanding more about the global C. auris situation, places where it’s set-up shop and really been able to expand, like in some places in India and Kenya it makes up 40% of the candidemias, so it on that — if you look at that old graph, I mean that pie chart of the species where I was talking about the albicans and the glabrata in this country, there you see 40%, so probably the majority of the candidemias, the bloodstream infections are actually caused by C. auris and that’s something we would like to not see happen. In South Africa in the private system 10% of their candidemias I think and climbing are due to C. auris. We know that there are thousands of infections in Venezuela. Limited data and diagnostic capacity to understand the extent, but we know it’s quite widespread. And now we know Colombia and Panama both have ongoing issues with Candida auris, and again we’re working with our colleagues in the Americas to try to put into place better infection control techniques. I already spoke to you about the UK situation. I don’t know if anyone happened to see some news reports today, but there’s actually a report that the UK problem with this fungus is in 55 hospitals across the country. So they are clearly seeing, although they’ve done a good job of controlling it in that original hospital that I spoke to you about it has found its way into different parts of the UK. And again our understanding is these are not strains from the UK, but again they were strains that had been introduced and then have done some local spread. It’s actually relatively few cases that we have heard about ongoing in South Korea and we’ve received no further word of isolates from Japan. And then, of course, major parts of the world are still unknown, like most of Africa and a lot of Latin America. So we’re still trying to get a handle on the global situation. Next slide? So clearly there’s a need and a desire to do further work and we encourage anyone to get engaged if you’re interested. Improved diagnostics is really important. Assessment of the diagnostic capacity of the microbiology labs and the hospital labs that you’re working with is also critically important. We want to expand our understanding of the epidemiology with specifics to risk factors for the really bad disease, this invasive infection, but also understanding if there are specific risk factors for colonization so we know how to potentially think about colonized people upfront before the bug actually hits. We obviously want to learn a lot more about resistance and whether this bug is virulent. One thing I can tell you about it based on some studies and talking with colleagues is that this organism is very happy when it’s resistant. So it is not something that tries to get rid of its resistance, it’s very happy being resistant. And, secondly, about virulence we’re still learning about specific virulence for this, but I will tell you that in talking to some colleagues in Pakistan, in South Asia, they really do feel that in many of their cases that Candida auris is actually causing mortality. It’s much harder for us to characterize that in our population in the US because, as I said, these are very healthcare experienced patients, but we’re getting the inclination from talking to colleagues where there are more than the usual risk factors for Candida these patients, indeed, do have a mortality associated with their infections. We obviously are concerned about the future and if there are triple resistant isolates spreading how do we actually treat those? I think the good news there is there are some new anti-fungal agents in the pipeline and some of those have new mechanisms and so it’s a good thing because I think the pipeline has been somewhat dismal for many years. The last new drug were the echinocandins that were introduced 15 some years ago. So I’m cautiously optimistic about the pipeline. I’d like to see more things moving in that direction so that when we need them we will have them available. One of the things that’s really challenging in both the bacterial and now the fungal world is the idea of de-colonization strategies, how do you really de-colonize a patient? And I think I put de-colonize in quotes because it can be really challenging and do you really know, and what are the steps we need to take to say, okay, someone is now negative for being colonized with Candida auris? I think we’re quite a ways from that, but we’re certainly working hard trying to think how can we de-colonize people and what is the role for different types of disinfectants? Finally, I think this just is another thing that is going to strengthen IPC and really evaluate the effectiveness of our various IPC interventions, which is critical to not only this pathogen but many others that we’re dealing with in our healthcare environments. And then on an aside, you know, we’re still puzzled a bit about the emergence and what is the environmental niche and the origins of Candida auris? We’ve not ever isolated this organism from the environment, so we’re still searching. Next slide? So, in summary, Candida auris causes invasive infections and in some parts of the world a lot of them with a relatively high mortality. We know it’s challenging to identify unless you have pretty modern technology, so the typical biochemical tests do not identify Candida auris. It’s often multi-drug resistant and in some cases, as I’ve mentioned, resistant to all three known anti-fungal drugs. And the big one is it’s transmitted in healthcare settings, readily transmitted in healthcare settings, again, setting up shop both on the patient’s skin and on surfaces in healthcare environments that make it a real challenge to get rid of. So surveillance and infection control is dramatically needed. You can find a lot of information and, again, we try to update our website as often as we hear about new things and reports and certainly as we get more reports about cases and their whereabouts. So please visit our website to get the most up-to-date information that we have. Next slide? And I want to say thanks for participating in this COCA call and during our first inaugural Fungal Disease Awareness Week. We want you to think fungus, oftentimes we don’t think fungus, and there’s certainly a lot of other fungal infections besides just Candida auris out there, but I’m thrilled that I was able to talk to you guys today about Candida auris. Next slide? So, again, this is a community effort in healthcare, as it always is when we’re combatting these pathogens. We need to know where it is so we continue to want help with surveillance, we want to raise awareness and we need your help with that, as well. And if a case is detected please get in touch with the local and state authorities, they’ll get us involved, and we’re really trying to take a very aggressive approach to the introduction of Candida auris in the US, seeing if we can actually contain and control and even eliminate in healthcare settings. Next slide? So I think that’s it. I want to thank everybody for your attention and I will be around for questions.

>> Thank you so much, Dr. Chiller. We really appreciate you providing our COCA audience with such a wealth of information on this emerging health threat. We’re going to move on to the question-and-answer portion of the call. It looks like we have quite a few questions coming in through the webinar system. Dr. Chiller, there’s a lot of questions regarding disinfecting the room with UV light, can you talk more about that?

>> Sure, be happy to. We don’t have a lot of information on UV light use in this country, but I can tell you talking to our colleagues in the UK they did not have success with that and I think they had done even some sort of in laboratory studies looking at UV and it did not do much. So we are not advocating the use of UV, again, we haven’t studied it ourselves, but based on what other people are telling us we would not recommend UV as a way in which to actually disinfect this organism.

>> Thank you. The next question is given that most clinical microbiology labs do not work-up yeast in urine or respiratory specimens does CDC recommend facilities do active surveillance to monitor for C. auris given the infection control implications of colonization?

>> Yes, that is a great question, and we’ve been just putting together some guidance that will recommend something along those lines. I think we have been concerned because we have seen, as I mentioned in my talk, some of these one-off cases of C. auris in these sort of nontraditionally speciated culture sites. And so that presents a challenge because then you have a patient that might be colonized and that could then spread and have that organism set-up shop in the healthcare facility and then spread to other. So, yes, we are working on sort of the logistics and thinking through what a recommendation would look like. I would again say that if you have a Candida in a nonsterile site and you’re able to get a quick species on it that would be warranted, certainly in the areas of risk. There are also some thoughts that could be given to taking a good medical history and understanding if that patient had come from any of these areas around the globe where we know Candida auris is really widespread, and that’s one of the reasons we’re trying to keep a map updated so that healthcare providers can understand a potential medical risk. It’s hard to say to everyone out there start speciating all your urine cultures. You all know how challenging that would be. We get a lot of Candida growing in urine and I would say 99% of it is not actually causing infection, but if it’s Candida auris as we’ve seen in a couple situations then we’re concerned about the potential that it could again set-up shop in the healthcare environment. So these are important thoughts and we are trying to put together a reasonable approach to actually doing those speciation.

>> Okay, thank you, Dr. Chiller. The next question is what was the outcome for patients who were infected with strains of C. auris that were resistant to all three classes of anti-fungals?

>> Yes, thanks for that question. Actually, there were very few and we really haven’t gotten outcomes on others that I think are probably still occurring. I mean I can tell you that the rate, that the mortality rate was around 70% to 75%. I don’t know the specifics of all those patients with triple resistance, but I think suffice it to say they did not do very well.

>> Okay, the next question is going back to cleaning the patients’ rooms, are there any comments on the use of accelerated hydrogen peroxide?

>> Yes, that’s a great question. And I’m intrigued by that option, and again back to our experience and talking to colleagues in the UK they did use different types of accelerated hydrogen peroxide machines to disperse that and they did find some success. Again, I can’t comment on use in our own hands yet, but we are interested in looking further into that option.

>> Okay, next question, any risk from antibiotics use in animals and over-the-counter medications, like cough syrup?

>> So I guess when you say risk from antibiotics you said animals, meaning that you might actually then set-up a reservoir for getting Candida auris? We really don’t know. We really don’t know much about, again, its origins and the environment. As of right now we have no reason to believe that animals are anywhere involved or over-the-counter medications or anything like that. These, again, in the United States so far are very medically experienced patients, so they’ve been in healthcare settings for long periods of time and have been exposed to lots of different procedures.

>> Okay, the next question, do you treat positive urine cultures as C. auris or if the patient is asymptomatic?

>> Yes, that’s again another great question about Candida. We know that Candida in the urine is for the most part not treated unless you really think there’s an ascending infection, and so generally Candida in the urine you can remove catheters, you can do different things to get rid of it and it doesn’t require treatment at all. We consider thinking of C. auris the same way, at this point we have no reason to believe that you need to treat these patients any differently. So you would only treat a Candida auris in the urine if you truly thought it was causing an infection. Again, we don’t have a lot of data yet on how to de-colonize, so really what you’re talking about is a Candida auris in the urine from a patient who is colonized essentially because they don’t actually have a urinary tract infection, and we don’t have any data on using anti-fungals in that arena yet but I think we need to be thinking in the future about as we assess de-colonization protocols, yes, what are the options? So we’re talking to people about that and trying to understand the best approach.

>> Thank you. Next question, what advice would you give to laboratories as to where to start with culturing for the yeast? Currently they’re only looking at sterile sites.

>> Yes, that’s that question, that brings up the previous question about the idea of looking for Candida species in the traditional nonsterile sites where you often as a microbiology lab will simply report a Candida. You know, again, I think we are looking hard at that, trying to balance the simple fact that if you start speciating all of your Candida from a microbiology lab you’re going to triple, quadruple the amount of speciation you’re doing. And I think that right now we don’t think that’s warranted. So what we’re thinking about is, yes, you should consider especially if you are concerned about any epidemiological risk factors, so previous hospitalizations in countries or in places where you know Candida auris occurs, then I would be pushing to get more info on the Candida species in that patient if they had it in a nonsterile site. But I think your typical patient where you have Candida culture in the urine it’s going to be difficult for us to recommend that you speciate that patient at this time given, thankfully, the very small numbers of infections that we have. But I do think thinking about their prior medical exposure and where that exposure happened is going to help direct you to actually deciding whether to speciate or not.

>> Thank you. Next question, are there any explanations for the number of cases seen in New York?

>> I mean, no, there are no obvious explanations besides the fact that as we know New York is a place that is quite large, lots of healthcare facilities, lots of people traveling in and out. So I think, as you can imagine, we’re seeing some of these cases in places where there is a big medical community and the possibility for people coming and going. And so that’s really the only explanation that we have at this time. And so big, big centers where people travel, but also where there are a lot of medical facilities are an obvious part of where we would think this thing would arrive and potentially emerge and that’s why we’re really focusing on education and getting people to be thinking about it. You know, identify it early and stomp it out because I think that’s going to be the best possibility for success in really containing, controlling and hopefully even eliminating this organism.

>> Thank you. Next question, I have an isolate of Candida dubliniensis from a patient’s tongue, had been treated twice prior to culture and had failed in culture obtained, would this be a concern to have this isolate further tested?

>> Well, certainly Candida dubliniensis can be a very Azole resistant species, so I’m not, in the sense of the C. auris I’m not worried about it being misidentified as C. auris per se, but they can be very challenging to treat in the oral mucosa. I think it would be great to get susceptibility testing and, in fact, now at least for candidemia the current Infectious Disease America guidelines do recommend that you do susceptibility testing on your Candida isolates, but certainly in a case like this when we’re challenged with an isolate that is not responding to therapy I would look and try to get a lab to do susceptibility testing and see if you can’t tailor your therapy to those susceptibility results.

>> Thank you. The next question is are hand gels the method of hand sanitizing, similarly, washing hands is the method of hand sanitizing for C. diff?

>> Yes, as of right now we are recommending the same infection control, hand hygiene methods that you would use for your current infection control practices in the hospital.

>> Thank you. The next question is for patients colonized with Candida auris but not infected is there any evidence for how long they remain colonized for and are there any recommendations for the length of time they need to be placed on contact precautions when in the healthcare setting?

>> Those are fantastic questions. I mean you can imagine I’m going to say don’t exactly know, but here’s what I can tell you based again on some of our own work, some of the work with states and colleagues, and then hearing from global partners. And that is, number one, this thing can stay on skin for months. I think, again, I said the longest I know I think is up to nine months with a patient remaining colonized. We don’t have good de-colonization protocols that are tested, so we don’t really know what we should recommend for de-colonization at this time. We hope to continue to work hard to think through that. And, as you all know, there are challenges in de-colonization protocols for bacteria and a lot of debate out there in what should or shouldn’t be done. And so now we’re moving that debate into the fungal arena and we’re going to be trying to figure out what to do with these patients. As far as how and when to isolate them and keep them in contact, precautions, et cetera, we haven’t developed in the standard practices for that yet because again all of our evidence is really based on talking to other people who are dealing with these outbreaks and dealing with these clusters. I do think that it’s important for the time being if you do have a patient with Candida auris just label them as such and keep them in contact precautions. We have seen some patients clear, so to speak, the colonization, for how long we don’t know, is this just something where we couldn’t find it and it will come back? So we’re learning really about this as we speak and don’t have any specific recommendations right now.

>> Thank you. Next question, should anti-fungal prophylaxis be used in abdominal surgeries and are there patients with epidemiologic risk factors or history of C. auris?

>> Yes, that’s another great question. I don’t think we feel that anti-fungal prophylaxis should be used in general in abdominal surgeries. I think it is somewhat of a case-by-case basis that one needs to think about this. Remember, one of the most important things about using anti-bacterials is stewardship, right? It’s using them appropriately. It’s very similar in the anti-fungal world, you know, I mean if we use too much anti-fungal we are going to select for these nasty resistant pathogens and select for them to actually become more and more prominent. So what we have seen epidemiologically in looking at Candida auris around the globe is that many, many, in fact, our initial studies all of the patients were Candida auris was isolated they were on an Azoles, mainly fluconazole, and you can see why in 90% of the Candida auris strains are resistant to fluconazole. So I don’t think anti-prophylaxis is the way to go at this time. There may be circumstances where it does make some sense. I do think that if there is this medical epidemiological risk that screening those patients, as we’ve talked about in the growing an axilla, makes sense and at that point knowing whether they have Candida auris or not will help you in furthering your patient management.

>> Thank you. Okay, we have time for one more question and that question is please describe recommendations for screening contacts, is this all patients on the same ward, only roommates, household contacts, et cetera?

>> Yes, that’s another great question. And we have some good guidance on that on our website, so I won’t go into excruciating detail. I do think, again, it depends a little bit on the situation. The way we’ve been generally recommending it so far as that, yes, patients that have been in the same room, absolutely. We have also recommended screening patients on like if it’s an ICU, in the general ICU pod, if that happens to be. I don’t think it has to go so far as the whole floor, especially if the patient has been essentially in that same area the entire time. We have looked, for example, when patients have traveled to the CT scanner or MRI and cultured those areas, looking for in that environment, and in a few cases have found it. So, again, I think it depends a little bit on how long you think that patient has been there, where that patient happens to have traveled, but doing your good typical infection control type investigation, yes, you’re going to want to screen certainly close contacts, certainly roommates, bedmates or people that have been subsequently in that bed and more than likely beyond at least in the pod or in the general vicinity, and then you can tailor some of that screening to those other places.

>> Thank you, Dr. Chiller, so very much. There’s a number of questions that, unfortunately, we were unable to address due to time constraints, however, for folks who have questions that were not answered by Dr. Chiller if you would please send those questions to us at coca@cdc.gov, again c-o-c-a at cdc.g-o-v, we’ll make sure Dr. Chiller provides responses to those questions, as well. And thank you, again, Dr. Chiller, for joining us today and presenting on such an important emerging health threat. We really appreciate that, and we appreciate everybody joining us today on this COCA call. The recording of this call and a transcript will be posted to the COCA website at emergency.cdc.gov/coca within the next few days. All continuing education for COCA calls are issued online through TCE online, the CDC training and continuing education online system, at www.cdc.gov/tceonline. Those who participated in today’s COCA call and would like to receive continuing education should complete the online evaluation by September 15th, 2017 and use course code WC2286. Those who plan to review the call OnDemand and would like to receive continuing education should complete the online evaluation by August 15th, 2019, also using the course code WD2286. To receive information on upcoming COCA calls subscribe to COCA by going to the COCA web page at emergency.cdc.gov/coca and clicking on the join the COCA mailing list link. Please be sure to join us for our next COCA call with our partner, the American College of Veterinary Preventive Medicine, ACVPM, which will take place on September 21st, 2017 at 2 p.m. Eastern Time. The topic of this call will be the Ecology of Emerging and Zoonotic Diseases. Also, you’re invited to join our like a COCA Facebook page at facebook.com/cdc clinician outreach and communication activity to stay connected to the latest news from COCA. Thank you, once again, for being a part of today’s COCA call. We hope you have a fantastic day. Thank you.

>> Thank you, guys.

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