Candida auris

{{Speciesbox

| image = Candida-auris 2016-250px.jpg

| genus = Candida

| species = auris

| authority = Satoh & Makimura, 2009{{cite journal |vauthors=Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H |title=Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital |journal=Microbiology and Immunology |volume=53 |issue=1 |pages=41–4 |date=January 2009 |pmid=19161556 |doi=10.1111/j.1348-0421.2008.00083.x | doi-access = free}}

| type_strain = DSM 21092{{cite web |url=https://www.dsmz.de/catalogues/details/culture/DSM-21092.html |title=Candida auris |publisher=DSMZ – German Collection of Microorganisms and Cell Cultures|access-date=2017-08-01}}

| synonyms =

}}

File:Proposed scheme for the emergence of Candida auris.jpg

Candida auris is a species of fungus that grows as yeast. It is one of the few species of the genus Candida which cause candidiasis in humans. Often, candidiasis is acquired in hospitals by patients with weakened immune systems. C.{{nbsp}}auris can cause invasive candidiasis (fungemia) in which the bloodstream, the central nervous system, and internal organs are infected. It has attracted widespread attention because of its multiple drug resistance. Treatment is also complicated because it is easily misidentified as other Candida species.

Candida auris was first described in 2009 after it was isolated from the ear canal of a 70-year-old Japanese woman at the Tokyo Metropolitan Geriatric Hospital in Japan. In 2011, South Korea saw its first cases of disease-causing C.{{nbsp}}auris. Reportedly, this spread across Asia and Europe, and first appeared in the U.S. in 2013.

DNA analysis of four distinct but drug-resistant strains of Candida auris indicate an evolutionary divergence taking place at least 4,000 years ago, with a common leap among the four varieties into drug-resistance possibly linked to widespread azole-type antifungal use in agriculture. However, explanations for its emergence remain speculative.

Identification and morphology

First identified in 2009, Candida auris is a species of ascomycetous fungus of the genus Candida that grows as a yeast. Its name comes from the Latin word for ear, aus (genitive auris).{{cite web |url=https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-qanda.html |title=Candida auris Questions and Answers |date=4 November 2016 |publisher=Centers for Disease Control and Prevention (CDC) |access-date=1 January 2017 |archive-url=https://web.archive.org/web/20170102010051/https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-qanda.html |archive-date=2 January 2017 |url-status=live}} It forms smooth, shiny, whitish-gray, viscous colonies on growth media. Microscopically, cells are ellipsoid in shape.

Clinical significance

Candida auris has attracted increased clinical attention because of its multiple drug resistance.{{cite journal |vauthors=Chatterjee S, Alampalli SV, Nageshan RK, Chettiar ST, Joshi S, Tatu US |title=Draft genome of a commonly misdiagnosed multidrug resistant pathogen Candida auris |journal=BMC Genomics |volume=16 |issue=1 |pages=686 |date=September 2015 |pmid=26346253 |pmc=4562351 |doi=10.1186/s12864-015-1863-z |doi-access=free }}{{cite web |url=https://www.cdc.gov/fungal/diseases/candidiasis/recommendations.html |title=Identification of Candida auris |publisher=Centers for Disease Control and Prevention (CDC) |access-date=2017-04-01}}{{cite news |url=https://www.nytimes.com/2019/04/06/health/drug-resistant-candida-auris.html |title=A Mysterious Infection, Spanning the Globe in a Climate of Secrecy |first1=Matt |last1=Richtel |author-link1=Matt Richtel |first2=Andrew |last2=Jacobs |author-link2=Andrew Jacobs (journalist) | name-list-style = vanc |date=6 April 2019 |access-date=7 April 2019 |issn=0362-4331 |newspaper=The New York Times |quote=C. auris is so tenacious, in part, because it is impervious to major antifungal medications, making it a new example of one of the world's most intractable health threats: the rise of drug-resistant infections.}}

In vitro, more than 90% of C.{{nbsp}}auris isolates are resistant to fluconazole{{cite journal |vauthors=Chowdhary A, Anil Kumar V, Sharma C, Prakash A, Agarwal K, Babu R, Dinesh KR, Karim S, Singh SK, Hagen F, Meis JF | display-authors = 6 |title=Multidrug-resistant endemic clonal strain of Candida auris in India |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=33 |issue=6 |pages=919–26 |date=June 2014 |pmid=24357342 |doi=10.1007/s10096-013-2027-1 |s2cid=14873835}} and a range of 3–73% of C.{{nbsp}}auris isolates are resistant to voriconazole,{{cite journal |vauthors=Rudramurthy SM, Chakrabarti A, Paul RA, Sood P, Kaur H, Capoor MR, Kindo AJ, Marak RS, Arora A, Sardana R, Das S, Chhina D, Patel A, Xess I, Tarai B, Singh P, Ghosh A | display-authors = 6 |title=Candida auris candidaemia in Indian ICUs: analysis of risk factors |journal=The Journal of Antimicrobial Chemotherapy |volume=72 |issue=6 |pages=1794–1801 |date=June 2017 |pmid=28333181 |doi=10.1093/jac/dkx034 | doi-access = free}} while other triazoles (posaconazole, itraconazole, and isavuconazole) display better activity. Of isolates, 13% to 35% were reported resistant to amphotericin B; however, most isolates are susceptible to echinocandins.

Treatment is complicated because C.{{nbsp}}auris is easily misidentified as various other Candida species.

{{cite web |title=Clinical Alert to U.S. Healthcare Facilities - June 2016 |publisher=Centers for Disease Control and Prevention (CDC) |date=2019-06-27 |url=https://www.cdc.gov/fungal/candida-auris/candida-auris-alert.html | access-date=2019-07-02}}{{cite web |title=Candida auris Clinical Update - September 2017 |publisher=Centers for Disease Control and Prevention (CDC) |date=2019-06-27 |url=https://www.cdc.gov/fungal/candida-auris/c-auris-alert-09-17.html | access-date=2019-07-02}} A brief outline of its clinical relevance {{as of|2016|lc=yes}}, understandable by general audiences, was published by the Center for Infectious Disease Research and Policy at the University of Minnesota.{{cite web |last=Dall |first=Chris | name-list-style = vanc |date=2016-06-29 |title=CDC issues warning on multidrug-resistant yeast infection |publisher=CIDRAP News |url=http://www.cidrap.umn.edu/news-perspective/2016/06/cdc-issues-warning-multidrug-resistant-yeast-infection}}

According to papers published from 2011 to 2016, mortality of people with C.{{nbsp}}auris bloodstream infections (BSI) ranged from 30 to 60%.{{cite journal |vauthors=Spivak ES, Hanson KE |title=Candida auris: An Emerging Fungal Pathogen |journal=Journal of Clinical Microbiology |volume=56 |issue=2 |pages=e01588–17 |date=February 2018 |pmid=29167291 |pmc=5786713 |doi=10.1128/JCM.01588-17 | editor-first = Colleen Suzanne | editor-last = Kraft | name-list-style = vanc}} Many of these people had other serious illnesses and conditions (comorbidities) that increased their risk of death.

In October 2023, the Faculty of Medicine of the University of Porto published a study which proved that hydrogen peroxide is extremely effective at killing C. auris in hospital surfaces, preventing it from spreading.{{Cite web |title=FMUP - FMUP researchers study 'weapons' in fight against deadly 'super' fungus |url=https://sigarra.up.pt/fmup/en/noticias_geral.ver_noticia?p_nr=89419 |access-date=2024-11-04 |website=sigarra.up.pt}}

Vaccine development

{{As of|October 2024}} there is no human vaccine against Candida auris.{{cite web | title=Candida Auris | publisher=Philadelphia Department of Public Health| date=8 August 2022 | url=https://hip.phila.gov/disease-control/diseasesconditions/candida-auris/ | access-date=21 March 2023}} Experiments involving the NDV-3A vaccine have successfully immunized mice against the fungus.{{Cite web |last=Harper |first=Rachel |date=7 August 2019 |title=Major step towards Candida auris vaccine developed |url=https://www.europeanpharmaceuticalreview.com/news/96289/major-step-candida-auris-vaccine/|url-status=live|archive-url=https://web.archive.org/web/20190807162507/https://www.europeanpharmaceuticalreview.com/news/96289/major-step-candida-auris-vaccine/ |archive-date=7 August 2019 |access-date=1 February 2021 |website=(European Pharmaceutical Review)}} The vaccine also improved the protective efficacy of the antifungal drug micafungin against C. auris infection in the mouse bloodstream.{{Cite journal |last1=Singh |first1=Shakti |last2=Uppuluri |first2=Priya |last3=Mamouei |first3=Zeinab |last4=Alqarihi |first4=Abdullah |last5=Elhassan |first5=Hana |last6=French |first6=Samuel |last7=Lockhart |first7=Shawn R. |last8=Chiller |first8=Tom |last9=Edwards |first9=John E.|last10=Ibrahim|first10=Ashraf S. |date=August 2019 |title=The NDV-3A vaccine protects mice from multidrug resistant Candida auris infection |journal=PLOS Pathogens |volume=15 |issue=8 |pages=e1007460 |doi=10.1371/journal.ppat.1007460 |issn=1553-7374 |pmc=6695204 |pmid=31381597 |doi-access=free }}

Genome

Several draft genomes from whole genome sequencing have been published.{{cite journal |vauthors=Sharma C, Kumar N, Meis JF, Pandey R, Chowdhary A |title=Draft Genome Sequence of a Fluconazole-Resistant Candida auris Strain from a Candidemia Patient in India |journal=Genome Announcements |volume=3 |issue=4 |pages=e00722–15 |date=July 2015 |pmid=26184929 |pmc=4505117 |doi=10.1128/genomeA.00722-15}} C.{{nbsp}}auris has a genome size of 12.3–12.5 {{abbr|Mb|millions of base pairs}} with a GC-content of 44.5–44.8%. The C.{{nbsp}}auris genome was found to encode several genes for the ABC transporter family, a major facilitator superfamily, which helps to explain its multiple drug resistance. Its genome also encodes virulence-related gene families such as lipases, oligopeptide transporters, mannosyl transferases and transcription factors which facilitate colonization, invasion, and iron acquisition. Another factor contributing to antifungal resistance is the presence of a set of genes known to be involved in biofilm formation.

More studies are needed to determine whether the phylogenetic divergence of C.{{nbsp}}auris clones exhibits region-specific patterns of invasiveness, virulence, and/or drug resistance.

Epidemiology

=Geographical differentiation=

The phylogenetics of C.{{nbsp}}auris suggest distinct genotypes exist in different geographical regions with substantial genomic diversity.{{cite journal |vauthors=Ben-Ami R, Berman J, Novikov A, Bash E, Shachor-Meyouhas Y, Zakin S, Maor Y, Tarabia J, Schechner V, Adler A, Finn T | display-authors = 6 |title=Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel |journal=Emerging Infectious Diseases |volume=23 |issue=1 |pages=195–203 |date=February 2017 |pmid=28098529 |pmc=5324804 |doi=10.3201/eid2302.161486}} A variety of sequence-based analytical methods have been used to support this finding.{{citation needed|date=August 2022}}

Whole genome sequencing and analyses of isolates from Pakistan, India, South Africa, Venezuela, Japan, and previously sequenced C.{{nbsp}}auris genomes deposited in the National Center for Biotechnology Information's Sequence Read Archive[https://www.ncbi.nlm.nih.gov/sra National Center for Biotechnology Information's Sequence Read Archive] U.S. National Library of Medicine, retrieved 31 May 2017 identified a distinct geographic distribution of genotypes.{{cite journal |vauthors=Lockhart SR, Etienne KA, Vallabhaneni S, Farooqi J, Chowdhary A, Govender NP, Colombo AL, Calvo B, Cuomo CA, Desjardins CA, Berkow EL, Castanheira M, Magobo RE, Jabeen K, Asghar RJ, Meis JF, Jackson B, Chiller T, Litvintseva AP | display-authors = 6 |title=Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses |journal=Clinical Infectious Diseases |volume=64 |issue=2 |pages=134–140 |date=January 2017 |pmid=27988485 |pmc=5215215 |doi=10.1093/cid/ciw691}} Four distinct clades separated by tens of thousands of single-nucleotide polymorphisms were identified. The distribution of these clades segregated geographically to South Asia (India and Pakistan), South Africa, Venezuela, and Japan with minimal observed intraregion genetic diversity.

Amplified fragment length polymorphism analysis of C.{{nbsp}}auris isolates from the United Kingdom, India, Japan, South Africa, South Korea, and Venezuela suggested that the London isolates formed a distinct cluster compared to the others.{{cite journal |vauthors=Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A, Ryan L, Shackleton J, Trimlett R, Meis JF, Armstrong-James D, Fisher MC | display-authors = 6 |title=Candida auris in a European hospital |journal=Antimicrobial Resistance and Infection Control |volume=5 |pages=35 |date=2016-10-19 |pmid=27777756 |pmc=5069812 |doi=10.1186/s13756-016-0132-5 | doi-access = free }}

Comparison of ribosomal DNA sequences of C.{{nbsp}}auris isolates from Israel, Asia, South Africa, and Kuwait found that the strains from Israel were phylogenetically distinct from those from the other regions.{{cite journal |vauthors=Miller R |title=Hospital design |journal=Hospitals |volume=40 |issue=7 |pages=91–4 |date=April 1966 |pmid=5324804}}

Chatterjee et al. wrote in 2015, "Its actual global distribution remains obscure as the current commercial methods of clinical diagnosis misidentify it as C.{{nbsp}}haemulonii."

=History=

File:Candida auria infections world distribution 2019.png

File:Map of Candida auris infections in US as of 2019.png

Candida auris was first described in 2009 after it was isolated from the ear canal of a 70-year-old Japanese woman at the Tokyo Metropolitan Geriatric Hospital in Japan. It was isolated based on its ability to grow in the presence of the fungicide micafungin, an echinocandin class fungicide. Phenotypic, chemotaxonomic and phylogenetic analyses established C.{{nbsp}}auris as a new strain of the genus Candida.{{cite web |url=http://www.mycobank.org/name/Candida%20auris |title=Candida auris |publisher=MycoBank|access-date=2017-04-02}}

The first three cases of disease-causing C.{{nbsp}}auris were reported from South Korea in 2011.{{cite journal |vauthors=Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH, Jang HC |title=First three reported cases of nosocomial fungemia caused by Candida auris |journal=Journal of Clinical Microbiology |volume=49 |issue=9 |pages=3139–42 |date=September 2011 |pmid=21715586 |pmc=3165631 |doi=10.1128/JCM.00319-11}} Two isolates had been obtained during a 2009 study and a third was discovered in a stored sample from 1996. All three cases had persistent fungemia, i.e. bloodstream infection, and two of the patients subsequently died due to complications. Notably, the isolates initially were misidentified as Candida haemulonii and Rhodotorula glutinis using standard methods, until sequence analysis correctly identified them as C.{{nbsp}}auris. These first cases emphasize the importance of accurate species identification and timely application of the correct antifungal for the effective treatment of candidiasis with C.{{nbsp}}auris.

During 2009–2011, 12 C.{{nbsp}}auris isolates were obtained from patients at two hospitals in Delhi, India.{{cite journal |vauthors=Chowdhary A, Sharma C, Duggal S, Agarwal K, Prakash A, Singh PK, Jain S, Kathuria S, Randhawa HS, Hagen F, Meis JF | display-authors = 6 |title=New clonal strain of Candida auris, Delhi, India |journal=Emerging Infectious Diseases |volume=19 |issue=10 |pages=1670–3 |date=October 2013 |pmid=24048006 |pmc=3810747 |doi=10.3201/eid1910.130393}} The same genotype was found in distinct settings: intensive care, surgical, medical, oncologic, neonatal, and pediatric wards, which were mutually exclusive with respect to health care personnel. Most had persistent candidemia and a high mortality rate was observed. All isolates were of the same clonal strain, however, and were only identified positively by DNA sequence analysis. As previously, the strain was misidentified with established diagnostic laboratory tests. The Indian researchers wrote in 2013 that C.{{nbsp}}auris was much more prevalent than published reports indicate since most diagnostic laboratories do not use sequence-based methods for strain identification.

The fungus spread to other continents and eventually, a multi-drug-resistant strain was discovered in Southeast Asian countries in early 2016.{{cite web |url=http://news.nationalgeographic.com/2016/11/deadly-fungus-drug-resistance-candida-auris-health-science/ |title=Fatal Fungus Linked to 4 New Deaths – What You Need to Know |date=7 November 2016 |publisher=National Geographic Society |author=Maryn McKenna |work=National Geographic|access-date=1 January 2017|archive-url=https://web.archive.org/web/20170102011122/http://news.nationalgeographic.com/2016/11/deadly-fungus-drug-resistance-candida-auris-health-science/|archive-date=2 January 2017|url-status=dead}}

The first report of a C.{{nbsp}}auris outbreak in Europe was an October 2016 in Royal Brompton Hospital, a London cardio-thoracic hospital. In April 2017, CDC director Anne Schuchat named it a "catastrophic threat".{{cite web |url=https://www.statnews.com/2017/04/21/superbug-cdc-fungus-candida-auris/ |title='Catastrophic threat': CDC chief fears a deadly superbug's spread |publisher=Stat News|access-date=2017-04-23 |first=Max |last=Blau| name-list-style = vanc |date=21 April 2017}} {{as of|May 2017}} the CDC had reported 77 cases in the United States. Of these, 69 were from samples collected in New York and New Jersey.{{cite journal |vauthors=Tsay S, Welsh RM, Adams EH, Chow NA, Gade L, Berkow EL, Poirot E, Lutterloh E, Quinn M, Chaturvedi S, Kerins J, Black SR, Kemble SK, Barrett PM, Barton K, Shannon DJ, Bradley K, Lockhart SR, Litvintseva AP, Moulton-Meissner H, Shugart A, Kallen A, Vallabhaneni S, Chiller TM, Jackson BR | display-authors = 6 |title=Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities - United States, June 2016-May 2017 |journal=MMWR. Morbidity and Mortality Weekly Report |volume=66 |issue=19 |pages=514–515 |date=May 2017 |pmid=28520710 |pmc=5657645 |doi=10.15585/mmwr.mm6619a7}}

{{As of|2019|8|31}} the number of cases of people having contracted C.{{nbsp}}auris in the United States had risen to 806, with 388 reported in New York, 137 in New Jersey and 227 in Illinois, according to the CDC.{{cite web |url=https://www.cdc.gov/fungal/candida-auris/tracking-c-auris.html |title=Tracking Candida auris |date=31 August 2019 |publisher=Centers for Disease Control and Prevention (CDC)|access-date=26 November 2019}}

Since it was first observed in the United Kingdom, it has spread to more than 20 NHS Trust hospitals and infected 200 people.{{cite news |url=https://www.independent.co.uk/life-style/health-and-families/drug-resistant-killer-fungus-candida-auris-nhs-hospitals-japan-life-threatening-difficult-to-a7904451.html |title=A killer fungus is spreading through UK hospitals – here's what you need to know about Candida auris |date=2017-08-21 |newspaper=The Independent|access-date=2017-08-27 |first=Daniel |last=Henk | name-list-style = vanc}}

{{As of|April 2019}}, the CDC has documented cases of C.{{nbsp}}auris from the following countries: Australia, Austria, Belgium, Canada, China, Colombia, France, Germany, India, Iran, Israel, Japan, Kenya, Kuwait, Malaysia, Mexico, the Netherlands, Norway, Oman, Pakistan, Panama, Russia, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Switzerland, Taiwan, Thailand, the United Arab Emirates, the United Kingdom, the United States, and Venezuela.

Candida auris fungus (C. auris) is a multi-drug–resistant fungal infection that spreads in hospitals and is extremely deadly—killing as many as one in three who get it.

:—Abby Haglage of Yahoo! Lifestyle,{{Cite web |last=Haglage |first=Abby | name-list-style = vanc |date=24 July 2019 |title=Deadly new fungal superbug is worrying doctors—here's what you need to know |url=https://www.yahoo.com/lifestyle/deadly-new-fungal-superbug-is-worrying-doctors-heres-what-you-need-to-know-172932479.html |publisher=Yahoo! Lifestyle |access-date=13 November 2019}} citing the Centers for Disease Control and Prevention{{Cite web |title=Candida auris: A Drug-resistant Germ That Spreads in Healthcare Facilities |url=https://www.cdc.gov/fungal/candida-auris/c-auris-drug-resistant.html |publisher=Centers for Disease Control and Prevention |date=21 December 2018 |access-date=13 November 2019}}

Arturo Casadevall, MD, PhD, and Molecular Microbiology and Immunology chair at Johns Hopkins Bloomberg School of Public Health stated:

What this study suggests is this is the beginning of fungi adapting to higher temperatures, and we are going to have more and more problems as the century goes on. Global warming will lead to selection of fungal lineages that are more thermally tolerant.

The COVID-19 pandemic has taken resources away from combating and tracking the fungus, which has led to outbreaks.{{cite news |last1=Richtel |first1=Matt |title=With All Eyes on Covid-19, Drug-Resistant Infections Crept In |url=https://www.nytimes.com/2021/01/27/health/covid-drug-resistant-infections.html?action=click&module=Top%20Stories&pgtype=Homepage |access-date=28 January 2021 |work=The New York Times |date=27 January 2021}} Shortages of personal protective equipment forced medical personnel to reuse of gowns and masks during the pandemic, which has contributed to the fungi's spread. In 2021, the CDC identified strains of Candida auris that were immune to all existing medications used to treat fungal infections.{{cite news |last1=Jacobs |first1=Andrew |title=Outbreaks of Untreatable, Drug-Resistant Fungus Spread in 2 Cities |url=https://www.nytimes.com/2021/07/23/health/superbug-fungus-cdc.html?action=click&module=In%20Other%20News&pgtype=Homepage |access-date=24 July 2021 |work=The New York Times |date=23 July 2021}} Research published in Annals of Internal Medicine tracking the spread of Candida auris from 2019 through 2021 revealed the fungus was present in over half of American states.{{cite news |last1=Richtel |first1=Matt |title=Deadly Fungus Spread Rapidly During the Pandemic, C.D.C. Says |url=https://www.nytimes.com/2023/03/20/health/candida-auris-us-fungus.html |access-date=21 March 2023 |work=The New York Times |date=20 March 2023}}{{cite news |last1=Roboson |first1=David |title=Strengthening Immunity and Promoting Well-being in the Face of Antifungal Resistance |url=https://www.uluyoga.com/candida-auris-and-yoga-strengthening-immunity-and-promoting-well-being-in-the-face-of-antifungal-resistance/ |access-date=22 March 2023 |work=Ulu Yoga |date=21 March 2023}}{{cite journal |last1=Lyman |first1=Meghan |last2=Forsberg |first2=Kaitlin |last3=Sexton |first3=D. Joseph |last4=Chow |first4=Nancy A. |last5=Lockhart |first5=Shawn R. |last6=Jackson |first6=Brendan R. |last7=Chiller |first7=Tom |title=Worsening Spread of Candida auris in the United States, 2019 to 2021 |journal=Annals of Internal Medicine |date=21 March 2023 |volume=176 |issue=4 |pages=M22–3469 |doi=10.7326/M22-3469|pmid=36940442 |s2cid=257632701 |pmc=11307313 }}

=Context=

Antimicrobial resistance in general is an increasingly common phenomenon. In 2010, two million people were reported to have contracted resistant infections in the United States {{ndash}} 23,000 fatally.{{efn-ua|According to official Center for Disease Control estimations.}} "[M]ore recent estimates from researchers at Washington University School of Medicine put the death toll at 162,000. Worldwide fatalities from resistant infections are estimated at 700,000 per year.{{Cite book |last=O'Neill |first=Jim | name-list-style = vanc |title=Tackling drug-resistant infections globally : final report and recommendations. |year=2016 |oclc=979367942}} C. auris is one of the many microbial contributors to this global AMR estimation.