The Multipronged Problem of Candida auris

Candida auris, a yeast-like fungus, is spreading globally, increasing the urgency for enhanced surveillance, new therapies, and more antimicrobial stewardship to combat its multidrug-resistant strains.

Since its discovery in 2009, Candida auris has been found in more than 50 countries across six continents, including Asia, Africa, and the Americas, according to the World Health Organization. In 2022, CDC reported 2377 clinical cases and 5754 screening cases of C auris in the United States.

Most fungi cannot infect humans because they cannot grow at 98 °F. But as the world warms, some fungi like C auris are adapting — and infecting humans. 

In September, The Lancet Microbe reported on three C auris isolates from a Singapore hospital belonging to a new clade (clade six), “which is phenotypically and genotypically distinct” from the first five clades, the authors write. In June, Microbiology Spectrum published a study about two unusual C auris isolates from a Bangladesh NICU in 2021. They were also assigned to clade six “with potential for international transmission,” the study authors noted.

C auris has all the hallmarks of “critical pathogen,” as defined by the World Health Organization in 2022. It increases morbidity and mortality for affected patients, is difficult to eradicate in hospitals, and can be treatment resistant.

As a result, infectious disease specialists are raising more awareness and advocating for greater surveillance of C auris colonization and disease in the hospital setting for high-risk patients.

Arturo Casadevall, MD, PhD, MS, is one of them. “C auris could be a problem in your hospital as fungal diseases are getting worse every year,” said Casadevall, chair of Molecular Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health in Baltimore. The increasing number of cases “is incremental, but when [we] look at the data over years, it is a growing problem. We may see more of these cases in the coming years.”

Expediting Diagnoses

Symptoms of C auris disease vary and can cause invasive infections, such as bloodstream or intra-abdominal infections. This is why Casadevall encourages infectious disease specialists to “always consider fungal disease when you are approaching an individual. The diagnosis is sometimes delayed because you don’t look for it,” he said.

C auris can also be misidentified in the lab “when using traditional biochemical methods for yeast identification. Accurate identification of C auris requires use of sequencing or mass spectrometry,” according to CDC.

C auris is typically found on the skin of colonized patients and can enter the body through invasive devices, incisions, wounds, and during surgery. Mostly, immunosuppressed patients are at risk for serious fungal disease, Casadevall said.

Invasive fungal disease can be life-threatening for hospitalized patients. In one review of 37 studies from 2011 to 2021, researchers found that overall mortality rates for C auris infections ranged from 29% to 62%, with 30-day mortality rates between 23% and 67%, Medical Mycology reported. Patients typically had a median hospital stay of 46-68 days, sometimes extending up to 140 days. Late-onset complications included metastatic septic issues, according to the study.  

Overcoming Treatment-Resistant Strains

A resilient yeast, C auris shows higher resistance to antifungal treatments compared to other Candida species, JAMA reported. Echinocandins are the first-line treatment for adults and children over 2 months old “and some of those therapies are already resistant,” said George Thompson, MD, professor of clinical medicine at the University of California Davis School of Medicine, Davis, California. The second line is liposomal amphotericin B (5 mg/kg daily), but it has toxicity problems, Thompson said.

New therapies sans toxicity are needed to treat C auris disease. Thompson, eg, served as the principal investigator in the ReSTORE trial to study a new therapy (rezafungin for injection). In March 2023, the US Food and Drug Administration approved the treatment for candidemia and invasive candidiasis in adults with limited or no alternative treatment options.

Thompson has observed that patients with C auris disease can present with “an infection in the urinary system with burning, pain, and bladder spasms. In the majority of cases of candida sepsis, the patients will have it in their blood stream with fever, chills, and sweats,” he said. The new treatment may clear the infection quickly, said Thomspon, who noted results published in The Lancet. 

Infection Prevention and Antimicrobial Stewardship

Institutions like University of Michigan Health (U-M Health) in Ann Arbor, Mich., have increased measures to tackle the issue from different angles. 

To address the broader issue of treatment-resistant fungal disease, U-M Health “has a robust antimicrobial stewardship program in place,” said Laraine Lynn Washer, MD, infectious disease physician.

The program includes oversight and restriction of various antifungals to avoid potential for overuse that could lead to increased risk for antifungal resistance. Use of echinocandins, for example, “requires prior approval by our antimicrobial stewardship team members,” said Washer, who is also Clinical Professor of Infectious Diseases and the Medical Director of Infection Prevention of Epidemiology at U-M Health.

Infection prevention measures entail screening hospitalized adult patients for risk factors for C auris, such as

• Overnight international hospitalization
• Recent stay in a long-term acute care facility
• Recent stay in a ventilator skilled nursing facility.

“If a patient has these risk factors, we perform testing to assess for colonization (presence of C auris without infection) by obtaining skin swabs from the axilla and the groin and asking our lab to perform PCR to identify genetic elements of C auris,” Washer said. “Patients who are transferred directly from another hospital ICU to our ICU also undergo testing for colonization.”

If a patient is identified with C auris, hospitals ought to perform screening tests using cultures or PCR “on other patients who may have overlapped in time and space with the patient such as hospital roommates,” Washer explained. 

Once in a hospital environment, the pathogen is hard to eradicate. C auris has a unique ability to be transmitted in the healthcare environment, is relatively heat tolerant, and is resistant to some common disinfectants, Washer added. The yeast can survive for over 2 weeks on plastic and months on skin, JAMA reported.

“Hospitals should partner with local and state level public health authorities in reporting cases of Candida auris and assist in any contact investigations as requested by public health authorities,” Washer advised.

Casadevall and Washer reported no conflicts of interest. Thompson has consulted and received research funding from Astellas, Basilea, Cidara, F2G, GSK, Melinta, Mundipharma, Pfizer, and Scynexis.