C. auris: Resistance is Everything

by Erica Mitchell | April 13 2019 | 1 Comment

C. auris-01The latest notorious pathogen to receive national press coverage is C. auris, a newcomer to the field and a threat with global implications. Joining the ranks of CRE, VRE, C. difficile and MRSA, this fungus is particularly sensational due to its novelty, it's seemingly spontaneous independent evolution on three continents, and it's high mortality rate. In today's post, we'll go over the basic story of C. auris, and end with some thoughts on how best to use a national story to bring about local change.

Candida auris joins a genus of yeast that has long co-habitated with humans. C. albicans, C. glabrata and others enjoy a commensal relationship with us, colonizing our gut and mucous membranes but kept in check by other members of our microbiome. Scientists developed antifungals to deal with fungus infections, and while not insignificant, the rate of hospital-acquired fungal infections was considered relatively low.

But then in 2009, a new strain of Candida was isolated, first in Japan and then South Korea. Named Candida auris, this species seemed to be resistant to a number of first-line antifungals, and proved difficult enough to eradicate that several very-ill patients died. A few years later, the same species led to outbreaks in India and among recent travelers to India in the UK (and spread to up to 72 others in one hospital alone). Also identified as C. auris, this species was nonetheless not the same strain as the one in Japan and South Korea. The following year, another C. auris outbreak takes hold of a private hospital in South Africa and spreading to others facilities in the region. Same species, but yet another strain. Two years later, an outbreak of C. auris is reported in Venezuela - and it is yet another strain. Four strains in just over five years, all evolved independently. Yet all had the same characteristic resistance to antifungal treatments, and all were involved solely in hospital-acquired infections (no community-acquired infections).

The Quest for New Antifungals
Fungi have their own Kingdom in the tree of life, setting them apart from plants, bacteria, and animals. One might easily believe fungi to be genetically close to plants or even bacteria, but in fact these eukaryotes are closer to animals than to any other Kingdom! Therefore, targeting their cells with a toxic substance puts surrounding animal cells (namely, ours) at risk. So far, antifungals take advantage of a key difference between animal and fungal cells membranes (the use of ergosterol instead of cholesterol) to create antifungals, but new targets are being investigated.

So what makes this species so scary? C. auris is not that virulent compared to its fellow Candida species and doesn't form the invasive hyphae that make C. albicans and others harmful. Other species can survive longer without a host, since C. auris doesn't form the hardy chlamydospores that persist in dry conditions. Even it's biofilm creation is sub-par, with the thickness reaching only 50% of other Candida species. And C. auris isn't nearly as widespread as other fungi, which can be found literally everywhere we go - it's only found in hospitals. So why is it so scary? 90% are resistant to at least one class of antifungals, and over 30% are resistant to all three classes of antifungal treatments.

The power of C. auris, the one that gives it the ability to kill 50% of its hosts within 90 days, and up to 60% of its hosts overall, is its ability to survive antifungal treatments. Most research seems to point to this strain evolving under the environmental pressures of broad-spectrum antifungals, giving the species with that specific mutation ample opportunity to flourish and spread. In those conditions, it didn't need to be extra virulent, or extra hardy, or even extra good at making biofilms. It only had to survive antifungals, and so it evolved work-arounds to each class of antifungal and therefore stayed in the host body long enough to do maximum harm. And even with its relatively modest survival time of 14 days on a dry surface, this is enough be transmitted to the next host (most C. auris infections are in fact exogenous). This is why the most common victims to C. auris are those with the weakest immune systems: The elderly, cancer patients, and infants, especially if any are receiving care in a long-term facility.

Unfortunately, this resistance also applies to some cleaning regimens. The most common hospital detergents, quaternary ammonium compounds (QACs), are useless against C. auris. UV radiation, which is already not as effective against fungi, require longer cycled times to kill C. auris. The CDC is currently developing cleaning protocols for C. auris, and in the meantime suggests using C. difficile protocols, including sporocidal disinfectants.

It's not every day that a resistant pathogen gets front-page news. Usually we might say that's a good thing, that "no news is good news." But in this case, while C. auris might be getting all the attention right now, those of us who work in the infection prevention field are well aware of the growing threat of all kinds of resistance. Getting public awareness to the subject can be fantastic - we need more people to understand that grave threat that awaits us in a post-antibiotic world. However, we need to make sure that public outcry is leveled at the correct target. We can all use this sudden pathogen celebrity to bring awareness about antibiotic stewardship, hand hygiene, and all the basic tenets of infection control and prevention. We can bring attention to new technologies that help reduce bioburden without leading to resistance, such as copper. While everyone is freaking out about C. auris, we can use this opportunity to inform this new audience to all the things they can do to make sure we stay in the antibiotic - and antifungal - era.

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