How Candida auris Became a Serious Global Health Threat and What We’re Doing About It
Just 2 years ago, if you attended ASM Microbe 2017, you might have noticed that everyone was suddenly talking about an organism called Candida auris. First isolated from the ear canal of a patient in a Japanese hospital in 2009, it had been found in just a handful of patients in 6 countries by 2015. Even an exhaustive dive into one of the largest fungal repositories in the United States found only four additional cases that had been previously misidentified and all occurred after 2009. Yet it was the talk of the conference in clinical and public health microbiology circles. By early 2018, I came across it while thumbing through an edition of Consumer Reports: apparently, it had gone mainstream. How had this once-rare pathogen suddenly become so well-known?
Following that first patient in 2009, C. auris was isolated from another 15 cases of otitis media and 3 cases of fungemia in South Korea between 2009 and 2011. Cases then appeared in India, South Africa, Venezuela and Kuwait from 2013 to 2014. By now, clinicians had taken notice of this novel species’ high rate of antifungal drug resistance, particularly to the azole class, and seeming ease of transmission. In 2015, collaborators in Pakistan reached out to the Centers for Disease Control and Prevention (CDC) and about 18 Pakistani isolates initially identified as Saccharomyces were found by CDC to be C. auris. Whole genome sequencing of an expanded isolate pool found a highly phylogeographic structure that suggested the near-simultaneous, independent emergence of four distinct clades: South Asian, South African, South American, and East Asian! C. auris reached the UK in 2015 at a cardio-thoracic center outbreak in London. Meanwhile in the United States, a clinical health alert issued by the CDC in June 2016 has prompted the discovery of 7 cases of C. auris in the States since 2013; by May 2017, there were 77 clinical cases in the U.S., with 45 additional cases from screening. The rapid spread of this pathogen had certainly become a worrisome trend. (Figure 1)
What Makes Candida auris so Important?
- It is HIGHLY drug resistant. And that is still underselling it. This is perhaps best exemplified by comparing it to the second most drug-resistant Candida species, Candida glabrata. The resistance rate among C. auris isolates to fluconazole, an azole class drug, is about 90%, compared to about 11% for C. glabrata, which is especially alarming when you consider that fluconazole-resistant Candida is among the most serious antibiotic-resistant threats listed by CDC! For amphotericin B, the resistance rate among C. auris isolates is about 30%, which may seem comparatively small…until you realize that it’s <1% in C. glabrata. Making matters worse, the etiology of C. auris resistance is not yet understood, though antifungal overuse has been speculated to be the cause. Thankfully, most isolates of C. auris remain susceptible to members of the echinocandin class of antifungals.
- It is easily spread. This is due to the high rate of transmission from person-to-person and indirect transmission through fomite contamination. It can colonize human skin, persist on hard surfaces for weeks, and is resistant to killing by many common disinfectants. For these reasons, we have seen a rapid global spread: as of April 30, 2019, C. auris cases have been found in 34 countries with 684 confirmed or probable clinical cases in the United States, mostly confined to the New York, New Jersey, and Chicago areas. Unsurprisingly, this also presents a great risk for outbreaks in healthcare facilities where there is a concentration of affected patients, contaminated surfaces, and an immune-compromised population.
- It is commonly misidentified. In fact, CDC has detailed algorithms that describe common diagnostic laboratory pipelines and what misdiagnoses can occur. C. auris is routinely misdiagnosed as Candida haemulonii, Candida famata, Candida lusitaniae, or Rhodotorula glutinis by biochemical testing methods including automated identification systems like the VITEK 2, BD Phoenix, and MicroScan WalkAway as well as the API 20C AUX testing strips for manual identification.
This combination of factors is causing considerable alarm for researchers, clinicians, and patients alike. Pathogens such as C. auris led to an executive strategy issued in 2014 for a national plan to combat antibiotic resistance threats. This was followed by a plan of action in 2015, which called for innovation of faster and better diagnostic tests and development of novel vaccines and other therapeutics to treat resistant infections like those caused by C. auris.
How Is Candida auris Identified?
It should come as no surprise that the sooner the causative agent of an infection is identified and its susceptibility patterns determined, the sooner appropriate therapy can be initiated. And it has been shown time and time again that there is a direct relationship between time to targeted therapy and survival of the patient. This is especially true for highly drug-resistant pathogens. So how are labs identifying C. auris?
C. auris will not make hyphae or pseudohyphae on cornmeal agar, unlike Candida guilliermondii, C. lusitaniae, and Candida parapsilosis, which are common misidentifications on the MicroScan. Unlike most Candida species excluding C. parapsilosis, C. auris will grow in high salt (10% NaCl) and at high temperature (40-42˚C). CHROMagar™ Candida, a proprietary selective media, can differentiate the Candida species, with C. auris appearing as white, red, pink or purple colonies (Figure 2). However, none of these methods used alone will identify C. auris. The only definitive methods recognized by CDC are:
- Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). This is typically undertaken on the Bruker MALDI Biotyper system since it was the first MALDI-TOF MS to earn FDA clearance last year. Until recently, identification of C. auris was sometimes made using MicrobeNet, an expanded, online database curated by CDC scientists and compatible with the Bruker platform.
- Sequencing of the D1-D2 region of the 28S or the Internal Transcribed Region (ITS) of rDNA by real-time PCR. The CDC even offers its own protocol using the MagnaPure 96, a robotic instrument for automated extraction and purification of nucleic acids, streamlining the process.
Finally, antifungal susceptibility testing is performed by broth dilution. Though CLSI has not established MIC breakpoints for C. auris, the CDC makes some recommendations for interpretation of susceptibility testing.
How Is Candida auris Treated?
As with the management of other invasive Candida infections, treatment with an echinocandin (caspofungin, anidulafungin, and micafungin) is recommended for initial therapy. This is especially appropriate since echinocandins are the sole holdout maintaining high rates of activity against C. auris. A switch to amphotericin B (a polyene) then fluconazole is recommended if the patient is unresponsive or the isolate is found to be resistant to echinocandins. Not to mention rigorous infection prevention and control measures to prevent transmission of C. auris, since it can colonize non-sterile body sites and then become invasive or spread to others. Such measures include:
- Contact precautions for infected or colonized patients, including placement in a single-patient room.
- Hand hygiene, especially for healthcare providers.
- Disinfection of equipment and facilities with appropriate disinfectants. For C. auris, this means the EPA’s List K products for Clostridium difficile spores.
- Screening of close contacts and at-risk individuals. The latter group consists of those with overnight stays in healthcare facilities outside the U.S. and infection or colonization with carbapenem-resistant Gram-negative bacteria.
The landscape of C. auris is constantly changing as it creeps its way across the globe: we are continuously learning about and improving our response to it. On the way, it has managed to capture the public’s interest as well, in more alarming ways for some than for others. C. auris continues to be an exciting organism for study and a dangerous pathogen in healthcare facilities.
The information from this blog post was sourced from the following:
Disclaimer: This was supported in part by an appointment to the Antimicrobial Resistance Laboratory Fellowship Program administered by the Association of Public Health Laboratories (APHL) and funded by the Centers for Disease Control and Prevention (CDC). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of CDC or APHL.
The above represent the views of the author and does not necessarily reflect the opinion of the American Society for Microbiology.