C. auris: ‘The more we see, the more resistance’

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“Most clinical laboratories still use a combination of macroscopic and microscopic morphology along with biochemical testing to identify Candida to a species level,” Dr. Hata says. “These techniques are not acceptable to identify C. auris accurately. The problem with this organism is that it can look like small yeast. Sometimes they are single cells, sometimes they cluster together. C. auris generally does not form pseudohyphae like most other Candida species, so it looks very different from the others when you are looking at it under a microscope.”

The biochemical profile of C. auris can also overlap with other Candida species, and the identification databases used by the commercial biochemical systems often do not contain C. auris, Dr. Hata adds. “There are some exceptions to this rule but, generally speaking, morphologic and biochemical methods should not be used to identify C. auris. The only good method we have, other than doing whole genome sequencing or conventional sequencing, which is considered the gold standard method, is that of MALDI-TOF.”

With a MALDI-TOF—either Bruker MALDI Biotyper or Vitek MS by BioMérieux—labs can generally identify C. auris, provided they have the updated databases, Dr. Humphries says. “That’s not so much of a challenge now as it was at the beginning of this emergence.” In 2018, both MALDI-TOF systems received FDA approval to include C. auris in their identification database.

Turnaround time can vary but the MALDI-TOF procedure itself is fast, Dr. Hata says. “Once you have a pure isolate available to run on the MALDI, the actual time on the instrument is very short. In our hands it’s less than an hour to do.” The main issue with MALDI-TOF is that although the cost of the test is quite low, the cost of the instrumentation is high. Says Dr. Humphries, “If the lab is not using a MALDI-TOF, it would need to send the sample to a reference lab or to a public health department lab to have confirmatory testing done on it.”

Incubation on Sabouraud dextrose agar for five days at 30°C.
Courtesy: Diana M. Meza Villegas, MS, SM(ASCP)CM, and Miranda E. Diaz, BS, SM(ASCP)CM, Mayo Clinic Florida microbiology laboratory.

Laboratories using FDA-approved versions of MALDI-TOF database libraries should be able to accurately identify C. auris. Using a manufacturer’s protocols, labs could also create their own custom research-use-only database library. The CDC, in collaboration with Bruker, offers an online tool that provides accurate classification of C. auris to the species level (www.cdc.gov/microbenet/index.html). Qualified laboratories can also obtain well-characterized isolates of C. auris from the CDC and FDA Antibiotic Resistance Isolate Bank to assist with verification or validation of FDA-approved or RUO organism identification databases (www.cdc.gov/drugresistance/resistance-bank/index.html).

“Developing our own database is what my laboratory did because we needed a method to be able to identify C. auris, but we didn’t have the FDA approval for C. auris yet,” says Dr. Hata.

Dr. Humphries notes the CDC’s online tools have practical tips on identification and how to interpret antifungal susceptibility test results. “There are no clinical breakpoints for this organism,” she says, “meaning there’s no official definition of what MIC [minimum inhibitory concentration] is susceptible and what MIC is resistant, but the CDC has guidance on an interim approach for handling that.”

Molecular sequencing can provide definitive identification of C. auris, but the financial investment needed and the technical requirements for sequencing tend to preclude routine use. “It is just the large academic medical centers or reference laboratories that do this, and not all of them have the bandwidth to routinely evaluate their sequencing databases for new fungal agents,” Dr. Humphries says.

C. auris is starting to be added to rapid multiplexed molecular testing systems. GenMark Diagnostics and BioFire Diagnostics have added C. auris to their blood culture panels—the ePlex BCID-FP (FDA cleared) and the BCID2 panel (pending FDA clearance), respectively. “However, there are no FDA-cleared screening tests at this point for C. auris, which makes identification of colonized patients challenging.”

At least one other technology is commercially available to test for Candida auris: magnetic resonance. The T2Cauris Panel by T2 Biosystems is a research-use-only panel that performs rapid detection of C. auris, C. duobushaemulonii, and C. haemulonii from blood, skin, and environmental swab samples. But the instrumentation is costly, Dr. Hata says, and applicability to identify a wide variety of Candida (including C. auris) is limited. “A lot of laboratories have to balance the cost of a given instrument with the number of different tests they can perform in order to make a good economic case for it.”

But hospitals do need better preparation for the C. auris pathogen, Dr. Humphries says, and testing is an obstacle. “If we were to wind up in an outbreak situation, hospitals don’t have good surveillance for patients who might be colonized but not necessarily infected. We don’t have a good way to screen for that right now, or to do a prevalence study. That’s one of the bigger challenges we’re facing.”

Says Dr. Hata: “Tests are very slow to come through the FDA approval process and we’d like to see more. It’s also important to have tests that are amenable to all levels of laboratories, not just reference laboratories, not just large commercial laboratories, but local, smaller laboratories. We have to have tests that are accurate, affordable, and can be performed in smaller labs.”

Meanwhile, the emergence of C. auris underlines the need for laboratories to make sure they don’t ignore yeast, Dr. Humphries stresses. “If you look at the CAP [Surveys] data, far more labs perform antibacterial susceptibility testing than do antifungal testing. I think that’s something that will change over time, but labs need to be aware that antifungal testing is an important patient care function and they should keep up with what’s going on in the literature.”

Anne Paxton is a writer and attorney in Seattle.