Update on Candida auris: Statistics, Detection, and a Phase 2 Trial

Candida auris was deemed nationally notifiable at the 2018 Council for State and Territorial Epidemiologists (CSTE) Annual Conference. The CTSE 2018 position statement cites up to 40% in-hospital mortality from invasive C auris infections, which have proven to be difficult to detect and treat, posing significant challenges in infection control and management.¹

As of October 31, 2018, the US Centers for Disease Control and Prevention (CDC) has reported 457 clinical cases of confirmed C auris infection with a majority in New York (>50%), New Jersey, and Illinois. In addition, there are 30 probable cases (from the same states) in which epidemiologic and presumptive laboratory evidence supports C auris as the pathogen, and 833 screening cases of patients found to be colonized with C auris.² Approximately 54% of cases of C auris are candidemia, and the remaining include various sources such as wounds, urine, sputum, and bile.

C auris is a budding yeast that forms white, pink, or red colonies, and can be difficult to distinguish from C glabrata. It does not form germ tubes and almost never forms short pseudohyphae; some strains form aggregate cells while others do not. In addition, traditional phenotypic methods can misidentify C auris as other Candida species, and therefore the CDC has developed laboratory staff fact sheets and algorithms which guide identification of C auris based on phenotypic laboratory method and initial Candida species identification.

Bruker MALDI Biotyper CA System database remains the only US Food and Drug Administration-approved device to identify C auris. Research-use-only systems include bioMerieux VITEK MS and Bruker MALDI Biotyper. Molecular sequencing of the D1-D2 region of the 28s rDNA of the Internal Transcribed Region can also identify C auris.

The table below summarizes common misidentifications based on phenotypic methods.

Phenotypic Method

Misidentification

VITEK 2 YST

C haemulonii

C duobushaemulonii

Candida spp not identified

BD Phoenix

C haemulonii

C cantenulata

Candida spp not identified

Microscan

C lusitaniae

C parapsilosis

C guilliermondii

C famata

Candida spp not identified

API 20C

Rhodotorula glutinis (absence of characteristic red color)

C sake

Candida spp not identified

RapID Yeast Plus

C parapsilosis

Candida spp not identified

Although C auris is commonly multidrug-resistant, the CDC recommends all isolates undergo susceptibility testing because of varying levels of resistance. There are currently no established minimum inhibitory concentration (MIC) breakpoints; thus, the CDC provides tentative MIC breakpoints based on related Candida species and expert opinion.

In the United States, 90% of C auris isolates have been found to be resistant to fluconazole, 30% resistant to amphotericin B, and 5% resistant to echinocandins.³ The CDC recommends echinocandins as first-line treatment for C auris using FDA-approved dosing recommendations for neonates, pediatrics, and adults. Liposomal amphotericin B (5 mg/kg/daily) is recommend if a patient is clinically unresponsive to echinocandins or has persistent candidemia for greater than 5 days. Treatment is not recommended for noninvasive, nonsterile sites such as respiratory tract, urine, and skin colonization, when there is no evidence of clinical infection. Infection prevention and control practices should be maintained for all C auris patients.⁴

Amplyx Pharmaceuticals announced on November 13, 2018, the first patient to receive their product APX001 in their phase 2 clinical trial “An Open-Label Study to Evaluate the Efficacy and Safety of APX001 (IV and oral) in Non-Neutropenic Patients with Candidemia, with or without Invasive Candidiasis, Inclusive of Patients with Suspected Resistance to Standard of Care Antifungal Treatment.” The trial is aiming to enroll 20 patients worldwide.⁵ APX001 is a prodrug of APX001A which has broad in vitro activity against Candida (including C auris), Cryptococcus, Aspergillus, Scedosporium, Fusarium, and members of the Mucorales order. APX001 is a glycosylphosphatidylinositol (GPI) inhibitor with a novel mechanism of action. In fungal cells, GPI mediates cell wall mannoproteins crosslinking to b-1, 6-glucan; APX001 inhibits Gwt1, a fungal enzyme which catalyzes the acylation step of GPI-anchored proteins of the fungal cell wall resulting in decreased cell wall integrity, biofilm formation, germ tube formation, and elicits fungal growth defects.⁶

Dr. Le is the director, clinical development and optimization at Accelerate Diagnostics, Inc. She practiced for 8 years in Brooklyn, New York, and previously served as the pharmacotherapy specialist, infectious diseases and residency program director, PGY2 Infectious Diseases Pharmacy Residency at The Brooklyn Hospital Center. She earned a PharmD from Wingate University School of Pharmacy, completed a PGY1 at The Brooklyn Hospital Center, and PGY2 ID pharmacy residency at Temple University Hospital.

References:

1. Council of State and Territorial Epidemiologists. Standardized Case Definition for Candida auris clinical and colonizations/screening cases and National Notification of C. auris case, clinical. https://cdn.ymaws.com/www.cste.org/resource/resmgr/2018_position_statements/18-ID-05.pdf. Published October 2018. Accessed November 17, 2018.
2. CDC. National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED) — Tracking Candida auris. cdc.gov/fungal/candida-auris/tracking-c-auris.html. Updated August 9, 2018. November 17, 2018.
3. CDC. National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED) - Recommendations for Identification of Candida auris. cdc.gov/fungal/candida-auris/recommendations.html. Updated June 22, 2018. Accessed November 17, 2018.
4. CDC. National Center for Emerging and Zoonotic Infectious Diseases (NCEZID), Division of Foodborne, Waterborne, and Environmental Diseases (DFWED) - Recommendations for Treatment of Candida Auris. https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html. Updated June 22, 2018. Accessed November 17, 2018.
5. Amplyx Doses First Patient in Phase 2 Trial of APX001 in Patients with Candida Infection [news release]. San Diego, CA: Amplyx Pharmaceuticals; November 13, 2018. https://amplyx.com/amplyx-doses-first-patient-in-phase-2-trial-of-apx001-in-patients-with-candida-infection/. Accessed November 17, 2018.
6. Hagar, CL, Larkin EL, Abidi, FZ, Shaw, KJ, & Ghannoum, MA. In vitro and in vivo evaluation of the antifungal activity of APX001A/APX001 against Candida auris. Antimicrob Agents Chemother. 2018 Feb 23;62(3). pii: e02319-17. doi: 10.1128/AAC.02319-17.