Candida auris: Understanding the Mystery Behind Outbreaks

Candida auris remains a mysterious fungal infection. Since it was first identified in Japan back in 2009, it has been spreading in localized outbreaks across 6 continents.

Most recently, the state of Mississippi reported in January that there were 6 total cases of C auris with 2 deaths and 37 people colonized with the fungus since November 2022. The cases were traced back to long term acute care facilities (LTAC) in the central part of the state.

According to the Centers for Disease Control and Prevention (CDC), a retrospective review of Candida collections found that the earliest known strain of the fungus dated back further to 1996 in South Korea. So, it has been with us for a number of years now, but thus far, there have been no definitive answers as to why these outbreaks occur.

“It is not entirely clear why we are seeing more Candida auris outbreaks,” David S. Perlin, PhD, chief scientific officer and executive vice president, Center for Discovery and Innovation (CDI) Hackensack Meridian Health, said. “One possibility is that there is a much broader use of antifungal agents around the world for both treating human disease as well as for controlling fungal outbreaks in agriculture. This may well be selecting for organisms for Candida auris, which can persist in the environment and readily adapt to stress situations induced by antifungal agents hence resulting in antifungal drug resistance.”

Interestingly, Perlin does see some parallels between fungal and bacterial infections and MDR.

“There are clades of Candida auris, for example, that have mono resistance, or mild resistance, or moderate resistance…during therapy you can see selection of a kind of canonical resistance,” Perlin stated.

CDC has outlined 3 main concerns about C auris infection, including: It is often multidrug-resistant; It can be challenging for labs to diagnose with standard laboratory methods, which can lead to misidentification and in turn lead to the incorrect treatment and management; and lastly, it can quickly lead to outbreaks in health care facilities. This last component, is especially concerning because C auris typically appears in hospitals and long-term facilities, affecting older patients and those who might already be diagnosed with serious health problems and might be prone to infections.

Perlin is an expert in drug discovery and drug resistance mechanisms, and he has helped develop novel therapeutics and diagnostics against high-threat bacteria, viruses, and fungi. He has published more than 320 papers and book chapters and has co-authored two books.

Perlin leads CDI, and his team has been involved in multiple studies involving C auris research. His laboratory is supported by multiple grants from the National Institutes of Health, pharmaceutical and biopharmaceutical sectors. Perlin and his group at CDI was among the first to develop a molecular diagnostic for C auris. “The key in developing a molecular diagnostic for Candida auris as it is for any organism is to identify those genetic signatures that distinguish it from other organisms.”

He said it was challenging for the existing commercial testing systems to distinguish the other species of Candida and were confusing the existing commercial tests.

Therapies
The mortality rate for this form of infection is high and that is due in part to the high level of multidrug resistance.

The CDC has its treatment recommendations for patients with C auris.

"Most strains of C auris found in the United States have been susceptible to echinocandins although reports of echinocandin- or pan-resistant cases are increasing. This organism appears to develop resistance quickly. Patients on antifungal treatment should be carefully monitored for clinical improvement. Follow-up cultures and repeat susceptibility testing should be conducted. Both recurrent and persistent C auris bloodstream infections have been documented," the CDC stated on its website.

Back in November, Jersey City, NJ-based Scynexis was awarded a grant to study the potential of their agent, SCY-247, for treatment of C auris. SCY-247 is a second generation fungerp, a triterpenoid class of antifungals, which represents the first new class of antifungal compounds since 2001, and is under development as a potential systemic therapeutic option. During that time, the company anticipated that the FDA may grant SCY-247 Qualified Infectious Disease Product (QIDP) and Fast Track designations for the IV and oral formulations of the agent.

The first generation fungerp, ibrexafungerp, formerly known as SCY-078, was FDA approved in December to treat vulvovaginal candidiasis (VVC) and prevent recurrent VVC.

Contagion spoke to Perlin who offered some insights into his lab’s research on C auris, their development of a molecular assay, various therapies, and the hope of further collaboration between laboratory professionals and clinicians.