The CDC is urging infection preventionists and their clinical colleagues to have a high index of suspicion for emerging Candida auris, a fungus that spreads more like bacteria, can be highly drug-resistant, and survives on skin and environmental surfaces for prolonged periods.

“We want people to think about this particular [pathogen] when they see Candida,” says Tom Chiller, MD, MPH, who is spearheading the CDC response as chief of the Mycotic Diseases Branch. “The key is if you are dealing with a Candida infection, it is important to try to figure out what that species is. As soon as you know it’s something common, then you’re good. But if it is not being identified get, it somewhere it can be identified. State labs can help; the CDC can help if needed. The other thing [clinicians] need to be thinking about is that this organism transmits differently [than typical fungi]. If you do identify it, you need to put contact precautions in place. Try your best to contain it — to make it the only case that shows up in your hospital.”

The term “superbug” has been somewhat overused in overwrought headlines as we approach the warning signs of a post-antibiotic era. However, if there is an emerging pathogen that warrants the term, it is C. auris, which was first reported as the etiologic agent of an ear infection (hence, the auris name) in 2009 in Japan. C. auris now has been identified in other parts of Asia, Africa, South America, and the United Kingdom. In the United States as of July 31, 2017, the CDC reported 112 cases of C. auris, with the bulk of them in New York (77) and New Jersey (23). Illinois reported four cases, and Massachusetts three. Other states reporting at least one case include Connecticut, Florida, Indiana, Maryland, and Oklahoma.

“These are all cases in hospitals or long-term acute care facilities,” Chiller says. “Right now, this is [infecting] a very medically exposed patient population. We haven’t gone into the community to actually look for it yet, because we are concerned about [inpatients]. We are focusing our efforts on hospitals and long-term care facilities. I think that of the cases we have now, close to 70% or so are from the blood. Many of the cases we are seeing in the U.S. are bloodstream infections. When you look globally, a lot of the cases are bloodstream, as well.”

The U.S., case counts reflect clinical infections with C. auris, but there also is a broader group of colonized patients. In four states that had clinical cases and then screened for colonization, a total of 120 patients were found to be asymptomatic carriers. The CDC emphasizes that recommended infection control measures are the same for both infection and colonization with C. auris, meaning asymptomatic carriers also would be placed in contact precautions. As with other multidrug-resistant pathogens, patients may be colonized for months and there is limited guidance on decolonization or removing isolation protocols. Healthcare workers certainly could have their hands transiently colonized long enough to risk cross-transmission, but they do not need to be tested for C. auris unless they are identified as a possible source of transmission to patients.

The continuing global emergence of this fungus has epidemiologists not known for exaggeration describing its unusual characteristics, which typically are not seen in fungi. These include spreading in hospitals more like bacteria; persisting in the environment unless powerful sporicidals are used, and acquiring resistance easily without any tradeoff in organism fitness.

To the latter point, some organisms that acquire drug resistance sacrifice some measure of vitality, losing the ability to sustain spread but occasionally occurring as an outlier. Much feared vancomycin-resistant Staphylococcus aureus is an example. Unfortunately, acquiring antibiotic resistance appears to exact no price from C. auris, with no sacrifice in virulence or transmissibility. Some global isolates have shown pan-resistance to all three classes of antifungal drugs, but none of those strains had yet been detected in the U.S. as of this report. The CDC recently updated its interim infection guidelines for C. auris, but generally continues to recommend rapid detection and isolation.1

“We are trying to get information out to the healthcare environment and workers as quickly as we know something,” Chiller says. “Right now, we are working on a clinical laboratory update because we want to start getting some information out about what physicians and hospitals must be thinking when it comes to doing colonization work or trying to screen someone who they think might be at risk of having this organism. We are constantly trying to update this, and I am hopeful we will have that coming out very soon.”

While this drug-resistant strain is still emerging, it is well to remember that currently some 46,000 healthcare-associated infections caused by other species of Candida occur annually in in the U.S. The broad emergence of C. auris, with its unusual propensity to thrive in the environment and develop drug resistance, would complicate this picture considerably, making fungal infections a public health threat on the level of the panoply of gram-negative organisms that have caused so much consternation in recent years.

Q&A with CDC Expert

Hospital Infection Control & Prevention (HIC) asked Chiller to describe the challenge of stopping C. auris in a recent interview, which is edited and summarized as follows:

HIC: How did this pathogen emerge so quickly — is it a distinct strain?

Chiller: Let me give what this is looking like from the epidemiological and case standpoint. We have been working with global partners for a number of years and that has really helped with whole genome sequencing. We have identified four distinct clades that seem to have developed in different parts of the world. How, when, and why those clades developed we don’t really know, but they are clearly distinct so it doesn’t appear they are related in any recent time period. In the U.S., all of the cases that have been seen so far relate to one of those four clades.

HIC: Is there concern that this could gain a foothold and become endemic in hospitals?

Chiller: In New York and New Jersey [hospitals] there does seem to be some local spread. We can monitor that, and some of those strains are slightly different, suggesting that they have been there a little while and have had a chance to evolve. We’re seeing in some places — like Oklahoma, for example — they rapidly identified one case and they got on it right way. That particular hospital did all kinds of containment and infection control measures, increased their disinfection practices, did some surveying around the hospital and didn’t find it. We feel pretty good about the fact that they probably had a “one-off” case. They reacted to contain, control, and eliminate any further spread within the hospital.

That is not the case in some of these clusters in New York and New Jersey, where they didn’t know it was there. It had an opportunity to spread and sort of set up shop like some of these other bad actors, Acinetobacter, CRE (carbapenem-resistant Enterobacteriaceae), and some of the other bacteria that we are trying to control. It’s acting very similar. It’s acting like a bacteria. That is what we are seeing right now in the U.S. There are a couple of places that continue to combat this and they are trying to take some extra measures to see if they can control and contain it. There are other places where it is a one-off introduction, probably from a traveler. Generally, what we have found is that it is travelers who are coming in for medical care. This is not just a random person who has traveled on a plane. This is someone who is medically ill in another country and is often coming here for continued medical care.

HIC: Can you speak to patient outcomes and mortality caused by these infections?

Chiller: This is a very medically experienced population. They are a very sick, lots of medical problems and lots of interventions. We know there has been around 30% mortality. Unfortunately, we don’t know how much of that is related to C. auris because these patients are sick with multiple medical problems. I can tell you the majority is not related. At least, I don’t think it is — it’s hard to say. We don’t know how much is truly associated with C. auris. We know they died with it, but we certainly don’t know if they died of it.

On a more global level, we are very interested and concerned about its ability to cause death and we know that in our country, candidemia in general — bloodstream infections — are major issues at our hospitals. In many hospitals, they are the number one cause of bloodstream infections. We know Candida species are deadly and we know there is an associated mortality of 20% to 30% in many cases. We just don’t know yet with C. auris in the U.S., but in talking to some global partners where there is a lot more C. auris in their countries — they are convinced that some of the mortality from those patients is directly due to C. auris. We haven’t been able to really document the direct evidence of that yet.

HIC: What level of drug resistance are you seeing?

Chiller: It’s interesting — there doesn’t seem to be a clade-specific resistance pattern. That suggests to us that resistance, unlike with a lot of other Candida, is acquired readily. They seemed to be able to acquire resistance easily, and when they have [become resistant] they are very fit. In other words, they are very content with that resistance. As you know, in the bacterial and pathogen world, we often think that acquiring resistance has sort of a fitness cost. They get this resistance and they are not as happy as they were when they didn’t have it. But that doesn’t seem to be the case with C. auris. These organisms are just as content being resistant.

So, the resistance that we’ve seen, unfortunately, is widespread. We see almost all of the isolates that we have been able to test, and we’ve talked to colleagues around the world — are resistant to fluconazole. That is one of the mainstay treatments of Candida through the years. About 30% to 50%, depending on where you are, are resistant to amphotericin B, an old class of drugs that is really important to have when you are treating Candida. And the first line therapy, which is a new class of drugs called echinocandins — depending on where you are — we are seeing 1% [resistant isolates] all the way up to 20% and 30% in some populations in Venezuela and Pakistan.

In our country, thankfully, we have had just a handful of isolates that are resistant to the amphotericin B. We have seen a case that we are fairly sure developed resistance while on echinocandin therapy, which is concerning. You hate to see bugs being able to acquire resistance while they are getting the appropriate treatment. Again, we are still trying to understand more about C. auris, how it acquires resistance so readily, and why it seems so fit when it has resistance. There are quite a few organisms that are resistant to two drugs, so at least we have one drug left. But there are a handful that we are finding that are resistant to all three drug classes. The problem with that is we really don’t have other drug classes to treat them with. Nothing in the U.S. has been pan-resistant yet, but we do know of some in South Asia. Certainly that is a concern when you are dealing with any organism. When it develops resistance to all known treatment modalities, you start struggling with how you are going to treat people. We are hoping to keep those highly resistant strains in check and figure out ways to combat them now before they become widespread.

HIC: The other unusual characteristic of this pathogen that has been cited by investigators is that it spreads more like bacteria than fungi. Can you elaborate on this?

Chiller: I keep telling healthcare workers, physicians, even my fellow infectious disease docs, don’t think of this particular Candida species like other Candida. Think of it like a bacteria because it is spreading readily within healthcare environments, unlike the typical Candida that we are very used to. Remember this is one of the most common bloodstream infections we have now in our hospitals. We are used to seeing candidemia, but generally the dogma is that those Candida are in our intestinal tract and are part of our normal microbiome. They are part of our normal flora, and in a hospital when you get exposed to surgery or get put on some broad-spectrum antibiotic that are mainly antibacterial, they kill the bacteria and Candida has a chance to overgrow. They translocate out into the bloodstream and cause problems. We often think of candidemia as a sort of of autoinfection. You are infected with your own strain and you don’t generally pass it from person to person or to the hospital environment.

In this case, C. auris is not acting like that, as far as we can tell. We still need to do more work, but it is acting like a nasty CRE or an Acinetobacter. It gets in a hospital environment, sets up shop, and can live on surfaces and equipment. It can be passed by hands as well as person to person and environmental surface to person. That’s how C. auris is acting. The paradigm has shifted for this particular yeast. One of our messages is to really get docs, nurses, pharmacists, everyone aware of this. When you see this Candida, don’t think [yeast] think bacteria because that is what it is acting like. That’s a challenging message to get out there, but that has really been our focus.

HIC: What about colonization and the whole issue of asymptomatic carriers that might be a reservoir for subsequent infections?

Chiller: That’s one of the things we are trying to elucidate and understand. In our web reports, we are reporting cases that are [infected] patients versus cases that are colonized. If you have a case of a patient that actually has an illness, we will often sample around that patient to understand whether this organism is being transmitted locally within the hospital and within the environment. We can then target cleaning and contain or get rid of it if we can. It definitely likes to colonize skin. We have people who had it on their skin for nine months, so it seems to be very [capable of] surviving on skin. Again, this is slightly different than the typical, usual Candida that is in our gastrointestinal tract. We also know that it survives really well on surfaces, plastic, floors, window sills, beds, desks. It can clearly survive in the environment and it is also more challenging to kill.

HIC: Thus, the change to a disinfectant with a sporicidal claim?

Chiller: The typical disinfectant we use in our hospitals — quaternary ammonium — does not work well at all against C. auris. Quaternary ammonium is sort of like the holy water of disinfectants — we use it everywhere. But it doesn’t kill C. auris. We really have to up our game to get this organism and use Clostridium difficile (C. diff )-type disinfectants. That is what we are recommending now in hospitals. That’s why it is important to identify colonized or [infected] cases so we know where it is so we can stomp it out. Just because you’re carrying it doesn’t necessarily mean you are going to become infected with it; in fact, that’s probably not the case. But it definitely means that the environment might be contaminated and we really want to eliminate it from healthcare settings as quickly as we can. Right now, we are recommending the highest level disinfectant, a C. diff-type sporicidal disinfectant. We are trying to look into the other possibilities for disinfectants that work.

REFERENCE

  1. CDC. Recommendations for Infection Control for Candida auris. July 28, 2017: http://bit.ly/2eI76e7.