Candida auris

15.08.21

Candida auris is a pathogen that has emerged as a global threat in recent years. It is the first human pathogenic fungus to be subject to international health alerts. The reason behind these concerns are –

• It is multi-resistant

• It is difficult to identify – often misidentified in standard laboratories

• It has been known to cause outbreaks in healthcare settings

• It colonises skin and hospital environment

There have been reports where C auris was resistant to all three classes of antifungal i.e. pan-resistance.

Candida auris was first reported in 2009 in Japan from the external ear canal of a patient. However, a retrospective review of microbiology cases in South Korea identified Candida auris from a case dating back to 1996.

Following this, many countries reported cases of C auris. As per CDC, up till February 2021, 49 countries have reported cases of C auris.

Here is a video showing when a country first reported a case of C auris [Forsberg 2019, Hu 2021]

Whole-genome sequencing (WGS) identified Candida auris have 4 different clades:

• Clade I (Southern Asia),

• Clade II (East Asia),

• Clade III (South Africa), and

• Clade IV (South America).

A potential fifth clade has been reported from Iran [Chow 2019].

There is very little difference between the strains in each clade, but vast differences exist between the clades – suggesting they emerged independently of each other.

Of these, three clades have been reported in the UK.

C auris was first reported from an ear sample, and many early cases were from chronic otitis media. It received its name from this association. Since then, it has been isolated from various other infections.

The risk factors associated with Candida auris infections are:

[Sekiyere 2018; Han Du, PLOS, 2020 ]

• Urinary catheters

• Arterial line, central venous access

• Parenteral nutrition

• Invasive medical procedures (surgeries) and devices

• Mechanical ventilation

• Hospital and intensive care unit (ICU) stays

• Prior or continual exposure to broad-spectrum antifungal or antibiotic therapy, especially tetracycline, minocycline and tigecycline.

• Chronic renal disease

• Diabetes mellitus

• HIV

• Elderly age

• Immunosuppressed state. Neutropenia.

Colonisation

Isolation of Candida auris from a non-sterile site does not always suggest infection. It is known to colonise the skin and, in rare instances, the gut, oral, and oesophageal mucosa. A salivary antimicrobial peptide histatin 5 has a potent antifungal effect on C. auris, making it difficult for this organism to colonise this area. [Han Du, PLOS, 2020]

• Tolerance to high temp (42 degree C), high salt concentration and osmotolerance – able to colonise and persist in various environments.

• Ability to form biofilms.

• Saps and lipases to degrade and invade host tissues

• Morphological transformation – it may form an aggregate of cells, which are less susceptible to antifungals (however, they are also less virulent).

• Resistance to multiple antifungal class

Candida auris is often misidentified as another organism by commercial systems.

As per PHE, any Candida spp. isolates associated with invasive infections and isolates from superficial sites in patients from high intensity/augmented care settings and those transferred from an affected hospital (the UK or abroad) should be analysed to species level.

Microscopy:

• C auris is indistinguishable from most other Candida species.

• Germ tube test negative budding yeast, some strains can form rudimentary pseudohyphae on cornmeal agar.

Culture:

• C. auris grows well at 40–42º C. Growth at 42 – 45⁰C may be useful to help differentiate it from many other Candida species especially C haemolounii, with which it is frequently confused.

• Colonies on CHROMagar may appear white, pink, red, or purple. Although it can be used for screening purpose it cannot be used as sole method for identification

CHROMagar Candida Plus:

Developed specifically to facilitate detection and identification of C. auris.

Performs well as a primary isolation medium and permits C. auris to be differentiated from over 50 other yeast species in Candida and related genera

Automated commercial system:

Automated commercial systems often misidentify C auris. CDC has presented a list of common misidentifications.

MALDI-ToF and molecular tests:

MALDI-ToF and molecular methods are considered the best identification methods.

MALDI-ToF: Bruker Biotyper and BioMérieux VITEK (MALDI-TOF) MS can identify C auris but the lab must ensure that the database is updated and contains C auris in it.

Molecular methods: sequencing the D1-D2 region of the 28s rDNA or the Internal Transcribed Region (ITS) of rDNA – are some methods that can be used. [Ref: CDC]

There are currently no established C. auris-specific susceptibility breakpoints. Tentative breakpoint from CDC

Mechanism of resistance

• Echinocandins (caspofungin, anidulafungin, micafungin) are considered as the first line therapy pending susceptibility test.

• However, resistance may develop quickly while a patient is receiving therapy and strains resistant to echinocandins have been reported. Clinical monitoring and repeat susceptibility testing from new isolates should be considered.

• As per CDC liposomal amphotericin B (5 mg/kg daily) could be considered if the patient is clinically unresponsive to echinocandin treatment or has persistent fungemia for >5 days.

• Combination therapy has not evaluated in clinical settings (CDC). PHE suggest if the urinary tract or central nervous system (CNS) is involved dual therapy may be necessary, and some antifungal classes do not have bio-availability in either urine or CNS.

• Terbinafine: Currently UK strains remain susceptible to the topical agents nystatin and terbinafine and it is possible that for the treatment of any future multi-drug resistant strains a regimen incorporating oral terbinafine could be considered [PHE].

• Multiple new drugs are being evaluated with potential activity against C auris. Novel antifungals ibrexafungerp have activity against C auris. [de Oliveira 2019, Billamboz 2021]