Candida auris: Dispatch From an Outbreak

Is there a silver lining to the recent outbreak of Candida auris? Medical mycologists like me have been alarmed by the remarkable spread of the multidrug-resistant yeast, which was first identified in 2009 in Japan and has spread throughout the world over the past year. But we have been encouraged by the renewed attention paid to the challenges associated with molecular diagnostics and antifungal drug development.

C auris was first identified in the United States in 2013, but it was not considered a common cause of disease until recently (the organism was never mentioned during my subspecialty training in infectious diseases). As of May 12, 2017, 77 clinical cases of C auris have been reported in the United States from 7 states; 51 cases have occurred in New York City,¹ where I work, including 3 cases at my hospital. The fungus can persist on surfaces in healthcare environments for prolonged periods of time, which has stifled efforts to curb the outbreak. Moreover, C auris is easily misidentified (most commonly as Candida haemulonii), and this can lead to inappropriate treatment and isolation decisions. 

Rapid identification of C auris is crucial in order to implement appropriate precautions and avoid transmission to other patients. Unfortunately, many laboratories are not set up to rapidly (or reliably) identify the organism. Our group is using a novel magnetic resonance (MR)-based assay to identify invasive candidiasis in high-risk patients, but the platform is unable to detect C auris. If the outbreak continues, future generations of this assay may have to be reconfigured.

It is unknown why C auris has recently emerged in so many different locations. Fortunately, isolates of C auris at my institution have not exhibited high levels of resistance to the 3 major classes of antifungal agents (triazoles, echinocandins, and polyenes). However, other institutions in the area have not been so fortunate. Although no established minimum inhibitory concentration (MIC) breakpoints exist for C auris, resistance testing conducted by the Centers for Disease Control and Prevention (CDC) demonstrated that nearly all isolates are highly resistant to fluconazole and more than half of C auris isolates were resistant to voriconazole.^2,3

It has been more than 10 years since a new class of antifungal agents has been introduced into clinical practice (echinocandins were last approved in 2006). The explanation for the delay is multi-factorial, and includes a chronic lack of investment in novel compounds as well as substantial regulatory hurdles associated with drug approval. Rigorous, statistically-valid, natural history-controlled, cross-over, and n-of-1 trials can establish the efficacy of new treatments for rare infectious diseases, but these studies are often limited because they are open-label, non-randomized, and rely on a relatively small number of patients. 

When the time comes to test a novel drug for the treatment of C auris in humans, we must take these challenges into account. Simply put, a randomized double-blind placebo-controlled trial will likely be infeasible and innovative approaches to trial design will be necessary. Thankfully, the time for reckoning may come sooner than many anticipated.

On May 11, 2017, SCYNEXIS, Inc. announced the publication of the results of a study of the activity of SCY-078, the first representative of a novel triterpenoid antifungal family against C auris.⁴ In this study, the Mycotic Diseases Branch of the CDC showed that SCY-078 has activity in vitro against C auris, confirming SCY-078’s broad spectrum of activity. The US Food and Drug Administration (FDA) has already granted Fast Track, Qualified Infectious Disease Product and Orphan Drug Designations for the drug for the indications of invasive candidiasis and invasive aspergillosis.⁵ SCY-078 combines the well-established activity of glucan synthase inhibitors (similar to echinocandins) with the potential flexibility of having intravenous and oral formulations (similar to azoles) while displaying activity against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains, and our work with the drug suggests that it achieves therapeutic drug levels in vivo. 

As investigational studies continue, healthcare workers on the front lines are left to confront a rapidly-spreading organism with limited treatment options. While we await enhanced treatment options, clinicians should use strict infection prevention and control measures, including: strict adherence to hand hygiene, contact precautions in a single room, dedicated patient care equipment, and environmental cleaning with the hospital-approved bleach-based products. For now, echinocandins are considered the drugs of choice for empiric treatment of confirmed or suspected C auris infection, but as the fungus evolves and clinicians continue to adapt, this recommendation may change.

Matthew W. McCarthy, MD, is an infectious disease specialist in the department of medicine at the Weill Medical College of Cornell University in New York, New York.

References

1. Candida auris. Centers for Disease Control and Prevention website. www.cdc.gov/fungal/diseases/candidiasis/candida-auris.html Updated May 18, 2017. Accessed June 9, 2017.
2. Tsay S, Welsh RM, Adams EH, et al. Notes from the field: ongoing transmission of Candida auris in health care facilities – United States, June 2016-May 2017. MMWR Morb Mortal Wkly Rep. 2017;66:514-515. doi:10.15585/mmwr.mm6619a7
3. Clinical Alert to U.S. Healthcare Facilities – June 2016. Centers for Disease Control and Prevention (CDC) website. Gwww.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html Updated June 24, 2016. Accessed June 9, 2017.
4. Potent in vitro activity of SCYNEXIS’ SCY-078 against multidrug-resistant fungal pathogen Candida auris further confirmed in an in vitro study conducted by the Centers for Disease Control and Prevention (CDC) [news release]. Jersey City, NJ: SCYNEXIS, Inc. http://ir.scynexis.com/releasedetail.cfm?ReleaseID=1026048 Published May 11, 2017. Accessed June 9, 2017.
5. SCYNEXIS, Inc. receives FDA Fast Track and QIDP Designations for intravenous formulation of SCY-078 for the treatment of patients with invasive fungal infections [news release]. Jersey City, NJ: SCYNEXIS, Inc. http://ir.scynexis.com/releasedetail.cfm?releaseid=952253  Published January 28, 2016. Accessed June 9, 2017.