Introduction:
In 2009, a 70-year-old woman in Tokyo, Japan was hospitalized with an ear infection that did not seem to improve with antibiotics [4]. The doctors found a fungus when they swabbed her ear and identified a new species of yeast, Candida auris. The first strain of the yeast was actually discovered in South Korea in 1996 but was not named until 2009 [3]. Little did epidemiologists know at the time just how devastating the yeast would become in healthcare settings. No one knew where it came from or how to prevent its spread [4]. Dr. Tom Chiller, chief of mycotic diseases at the United States Center for Disease Control and Prevention (CDC), says it is the most difficult pathogen they have seen – as it is more infectious and more difficult to kill than even the Ebola virus [4]. Due to the increasing number of infections identified around the world, the CDC now calls Candida auris an emerging fungal pathogen that has become a global health threat [2].
Yeast Behavior:
Yeasts are fungi that are naturally found in the environment, usually inhabiting warm and damp environments [4]. Yeasts normally only infect the people they inhabit. However, C. auris developed the ability to survive on cool external skin and object surfaces. This allows it to act like nosocomial bacteria, contaminating hospital surfaces and tools, spreading easily between humans and becoming increasingly difficult to eradicate even in hospitals with extensive infection control methods [3]. C. auris is an ascomycetous fungus, growing as a yeast, forming smooth, pale grey viscous colonies on its host [5]. But in the case of C. auris, it behaves like a bacterium, has the ability to adapt to its environment, spreads like a bacterium and resists antifungal drugs. In these ways, it appears to be a cross-species shift [4].
C. auris is the most invasive of the Candida species, causing the most severe fungal infections currently in existence [5]. It causes bloodstream infections, wound infections, and ear infections. It has been isolated in respiratory and urine samples, but it is unclear if it causes infections in the lung or bladder [2]. C. auris can infect the bloodstream and lead to fungemia, capable of spreading throughout the body and damaging the central nervous system and internal organs, which can lead to organ failure, coma and death [5]. In 30-40% of C. auris cases, the infections have been fatal. Case fatality appears to be dependent on the previous health condition of the patient [2]. Symptoms of C. auris infection include fever and chills, sepsis, coma, organ failure, and lack of response or improvement following antifungal treatment [5].
A different Candida species, Candida albicans, is the most frequently isolated Candida species in clinical settings, but differs from C. auris in several ways [5]. C. albicans, a common yeast that lives in the gut without causing harm, has mild symptoms compared to C. auris, and cannot be transmitted between people. Although overgrowth can cause digestive problems, skin conditions, hormonal disruption and vaginal thrush, this can all be treated with a variety of antifungal medicines or with a special diet. C. auris became more easily identified recently as it grew more resistant to antifungal drugs compared to its counterpart C. albicans [5].
Global Spread:
Since the first identified C. auris infection in Japan in 2009, more patients across the world have developed the same infection, equally resistant to antifungals; the yeast spread around the world with no connection between any of the patients [4]. The CDC performed whole genome sequencing of C. auris to provide detailed DNA of strains from eastern Asia, southern Asia, southern Africa and South America [2]. These strains were found to be genetically similar within regions, but different across continents. This suggests the yeast did not spread by transmission but that it evolved independently in multiple areas across the world at about the same time. C. auris has now become a global threat because it has spread to 27 countries [4]. This worldwide spread of resistant C. auris is due to increased resistance toward antifungal drugs, explained by the widespread over-prescription of antifungal medication. Microbes, including yeasts, can adapt in ways that allow them to become resistant, and those that become stronger and resistant have the opportunity to survive, reproduce, and spread [5].
Individuals at Risk:
It is very unlikely that routine travel to countries with previous C. auris infections would increase someone’s chance of getting infected, unless they were seeking medical care or foreign hospitalization [2]. Infections of this yeast occur primarily in patients who are hospitalized or who are immunocompromised. In fact, most infected patients, and all those who died from C. auris infection, had been previously hospitalized for another illness [4]. Those most at risk for C. auris infections are patients who have been hospitalized for a long time and are immunocompromised, regardless of age [2]. Those with central venous catheters or other lines or tubes entering the body, such as breathing, feeding tubes or intravenous fluids are particularly susceptible. Other risk factors for infection include patients with recent surgeries, transplants, or with diabetes or cancer [3], those living in nursing homes and previous use of antibiotics or antifungal medications [2].
Despite the threat of C. auris, only a limited population – those hospitalized or in nursing homes – is at risk of infection, and those patients should be getting the costliest protection [4]. However, facilities may not be able to hire adequate health workers or enforce infection-protection procedures, making it difficult to detect C. auris in patients before the yeast enters their facility.
Medication & Treatment: [4]
When patients are diagnosed with C. auris infections, they are provided with fast-acting antifungal medication and must be closely monitored with treatment because of the yeast’s ability to be highly resistant to medication and develop resistance quickly [3]. Patients must also be monitored because the yeast can live on skin after treatment, requiring continued protective hygiene practices.
According to the CDC, 90% of global C. auris infections are resistant to azoles, 30% are resistant to amphotericin, and up to 20% are resistant to last-option echinocandins [4]. Fungal infections are not a high priority in medical research, so few drugs have been created or approved to treat them. As mentioned, there exist only three drug classes for antifungals, with a few drugs each, compared to a dozen classes and hundreds of antibiotics for bacteria. In cases of C. auris infection, the CDC recommends combination treatments with three antifungals: anidulafungin, caspofungin and micafungin [3], and in some cases, the yeast is already resistant to all three [2]. Azoles are the first-choice antifungal treatment, with amphotericin as the backup option, administered only intravenously. Unfortunately, amphotericin is so toxic – causing severe fever and chill reactions – that use is avoided if possible [4]. The last class of intravenous antifungal drugs available to use against C. auris is echinocandins. Echinocandins include caspofungin (Merck’s Cancidas), anidulafungin (Pfizer’s Eraxis) or micafungin (Astellas’ Mycamine), if those do not work, toxic amphotericin B is used [5].
Lab Identification:
Patients with C. auris infections are often already very ill, making it difficult to distinguish their symptoms from other medical conditions [3]. C. auris infections, like other Candida infections, are usually diagnosed by blood or body fluid cultures [2]. But C. auris is harder to identify because it can be confused with other types of yeasts. Studies have shown that among patients who carried the yeast, more than 80% were misidentified at first, presumed to have another type of yeast [4]. Recently, the CDC published a guide for laboratories, explaining the mistakes made by seven different testing methods for identifying the yeast. To identify C. auris, a special lab test called matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) is used [3]. However, it takes several days to test for C. auris with special equipment, and in that time it can easily spread to others [5].
Defense Strategies:
Considering how highly resistant C. auris is, hospitals will have to turn to high standards of hygiene to avoid spread of the yeast [5]. Simple solutions such as cleanliness may be the most effective and practical, including wearing gloves and gowns and washing hands [4]. However, good hygiene may be harder to enforce in hospital facilities with large staff, especially compared to the ease of treating infections with medication. Unfortunately, even the best hygiene practices may not be enough. An outbreak of the C. auris in a London hospital in 2015 serves as an example of just how pervasive the yeast can be [4]. The hospital identified cases of infection and took all necessary precautions; these included wearing gloves and gowns, patient isolation, swabbing those in contact or in the same room as the patient, bathing the patient twice a day with disinfectant including mouthwash and dental gel, washing the patient’s room three times a day with diluted bleach, and after patient discharge, using a bomb with hydrogen peroxide vapor to sanitize the room and equipment. Despite all precautions taken, the yeast still persevered. Some of the last defenses to use against C. auris include patient isolation and use of chlorine bleach to kill C. auris. Evidence suggests quaternary ammonium cleanser commonly used in hospital disinfectants does not work [4]. Other protective steps include using disinfectant effective against Clostridium difficile spores – the strongest available disinfectant. The most important steps to prevention include protecting those most vulnerable to infection – specifically those who are immunocompromised or who have tubes entering the body – and limiting over-prescription of antibiotics and antifungals to patients because they weaken the immune system and lead to resistance [3].
Future Challenges:
Despite the possible hygiene and prevention strategies to use against the yeast, C. auris still poses a great challenge for the future of healthcare facilities. The CDC is highly concerned with three aspects of the yeast [1]. First, that C. auris is resistant to multiple antifungals classes commonly used to treat Candida infections. Second, that it is difficult to identify C. auris with standard lab methods and that it can easily be misidentified without very specific lab technology, leading to inappropriate management of infections. And finally, that it causes outbreaks in healthcare settings where it is extremely important to correctly identify the yeast to take special precautions against it [1].
Sources:
[1] “Candida Auris.” Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 23 July 2018, www.cdc.gov/fungal/candida-auris/index.html.
[2] “General Information about Candida Auris.” Centers for Disease Control and Prevention, U.S. Department of Health & Human Services, 14 Sept. 2017, www.cdc.gov/fungal/candida-auris/candida-auris-qanda.html.
[3] Levine, Hallie. “The Deadly Yeast Infection You Must Know About.” Consumer Reports, Consumer Reports, 27 Feb. 2018, www.consumerreports.org/yeast-infection/deadly-yeast-infection-candida-auris/.
[4] Mckenna, Maryn. “The Strange and Curious Case of the Deadly Superbug Yeast.” Wired, Conde Nast, 13 July 2018, www.wired.com/story/the-strange-and-curious-case-of-the-deadly-superbug-yeast/.
[5] Richards, Lisa. “Candida Auris: The Rise Of A Fungal Superbug.” The Candida Diet, Perfect Health, 29 Nov. 2017, www.thecandidadiet.com/candida-auris/.