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ARTICLE

Candida Auris: The Rise of a New Fungal Threat

AUG 15, 2017 | RYAN W. STEVENS, PHARMD, BCPS, AND WILLIAM BARANY, PHARMD
Antifungal resistance in C. auris is mediated through genome mutations and by the organism’s ability to form biofilms. Genome analysis of C. auris has revealed several amino acid substitutions within the Erg11 gene which encodes the fungal cytochrome p450 enzyme that is targeted by azole antifungals.2 Mutations within the gene prevent azole binding and confer resistance. Interestingly, this same mutation has been found in C. albicans and similarly results in high level resistance to fluconazole. Other resistance mechanisms to other antifungal agents by C. auris have yet to be described. Additionally, C. auris readily forms biofilms on polymeric surfaces. In vitro studies have found that caspofungin, while effective against planktonic C. auris cultures, is inactive against C. auris biofilms.9 Other Candida species like C. albicans are also known to form biofilms, but typically remain highly susceptible to caspofungin. Biofilm formation makes re­moval of catheters and other indwelling lines critical in the management and prevention of systemic C. auris infections.  

There are no formal treat­ment guidelines published specifically for the prevention and management of C. auris infection. Several agencies, including the CDC, have published interim recommendations for the diagnosis and management of C. auris based on clinical practice experi­ence and the limited case se­ries that have been published so far.8 The CDC recommends that an echinocandin be used for empiric therapy. If patient do not respond to empiric echinocandin therapy, they should be switched to ther­apy with liposomal amphotericin B. Dosing recommendations are included in these interim guidelines, and given the severity of these infections, a careful evaluation of patient-specific phar­macokinetic factors is warranted.8 There are no pub­lished recommendations that advocate for empiric dual antifungal treatment. C. auris is not specifically men­tioned in the 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis; however, the CDC’s recommended em­piric treatment regimens for C. auris align with the ID­SA’s 2016 candidiasis guidelines which also recommend that an echinocandin be used as the first line agent for the initial therapy for treatment of invasive candidiasis in non-neutropenic patients.10  

While much about C. auris and its mechanisms of antifungal resistance have yet to be described in full, case reports and descriptions of its virulence show that it will likely pose a significant challenge to clinicians across the globe as it continues to emerge. Further research, as well as continued development of novel antifungal agents, will be necessary to effectively treat and prevent the spread of this emerging pathogen.
 
Dr. Stevens graduated with a doctor of pharmacy from the University of Montana in 2010. He is the infectious diseases clinical pharmacy specialist at Providence Alaska Medical Center, where he developed and imple­mented a comprehensive antimicrobial stewardship program in 2013. He is an active member of SIDP.

Dr. Barany graduated with a bachelors of science in marine biology from Western Washington University in 2010. He received his PharmD from the University of Washington School of Pharmacy in 2016. He is currently a PGY1 pharmacy practice resident at Providence Alaska Medical Center in Anchorage, Alaska.

References:
  1. Global emergence of invasive infections caused by the multidrug-resistant yeast Candida auris [news release]. Atlanta, GA; Centers for Disease Control and Prevention; June 24, 2016. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html. Accessed April 7, 2017.
  2. Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analysis. CID. 2017;64(2):134-140. doi: 10.1093/cid/ciw691.
  3. Centers for Disease Control and Prevention. Candida auris: questions and answers. Centers for Disease Control and Prevention website. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-qanda.html. Published November 4, 2016. Accessed April 10, 2017.
  4. Centers for Disease Control and Prevention. Candida auris. Centers for Disease Control and Prevention website. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris.html. Published November 4, 2016. Accessed April 10, 2017.
  5. Centers for Disease Control and Prevention. Notes from the field: Ongoing transmission of Candida auris in Health Care Facilities – United States, June 2016-May2017. Centers for Disease Control and Prevention website. https://www.cdc.gov/mmwr/volumes/66/wr/mm6619a7.htm. Published May 19, 2017. Accessed May 19, 2017.
  6. Vallabhaneni S, Kallen A, Tsay S, et al. Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016. Am J Transplant. 2017;17(1):296-299. doi: 10.1111/ajt.14121.
  7. Clancy CJ, Nguyen MH. Emergence of Candida auris: an international call to arms. CID. 2017;64(2):141-143. doi: 10.1093/cid/ciw696
  8. Centers for Disease Control and Prevention. Candida auris interim recommendations for healthcare facilities and laboratories. Centers for Disease Control and Prevention website. https://www.cdc.gov/fungal/diseases/candidiasis/recommendations.html. Published November 4, 2016. Accessed April 10, 2017.
  9. Sherry L, Ramage G, Kean R, et al. Biofilm-Forming Capability of Highly Virulent, Multidrug-Resistant Candida auris. Emerging Infect Dis. 2017;23(2):328-331. doi: 10.3201/eid2302.161320.
  10. Pappas PG, Kauffman CA, Andes DR, et al. Clinical practices guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. CID. 2016;62(4):409-17. doi: 10.1093/cid/civ1194.


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