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'''This page is describing the Candida auris infection. For more information on the microorganism [[Candida auris|click here]].'''
 
==Overview==
''Candida auris'' is a fungus, recently described as a rare cause of fungal infection with significant resistance to [[antifungal medications]].<ref name="pmidPMID 24357342">{{cite journal| author=Chowdhary A, Anil Kumar V, Sharma C, Prakash A, Agarwal K, Babu R et al.| title=Multidrug-resistant endemic clonal strain of Candida auris in India. | journal=Eur J Clin Microbiol Infect Dis | year= 2014 | volume= 33 | issue= 6 | pages= 919-26 | pmid=PMID 24357342 | doi=10.1007/s10096-013-2027-1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24357342  }} </ref> It was first described in the year 2009 in Japan,<ref name="pmidPMID 27832049">{{cite journal| author=Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J et al.| title=Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016. | journal=MMWR Morb Mortal Wkly Rep | year= 2016 | volume= 65 | issue= 44 | pages= 1234-1237 | pmid=PMID 27832049 | doi=10.15585/mmwr.mm6544e1 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27832049  }} </ref> and since then, reports of ''C. auris'' infection has been published from several countries.<ref name="pmidPMID 27832049" /> However, retrospective testing of collected isolates show the earliest known infection with C. auris occurred in South Korea in 1996.<ref name="cdc2"/><ref name="pmid21715586" /> Serious and prolonged outbreaks have been documented with data showing an innate resilience of ''C.auris'' for survival, persistence in the clinical environment with the ability to rapidly colonize patient's skin, and high transmissibility within the healthcare system.<ref name="pmidPMID 27777756" /> An outbreak of over fifty cases over a sixteen month period in a cardiothoracic center in London is the first reported case, and the largest outbreak in Europe.<ref name="pmidPMID 27777756" /> The precise mode of transmission within the healthcare facility is unknown.<ref name="cdc1">Centers for Disease Control and Prevention. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html Accessed on November 11th, 2016. </ref><ref name=cdc2>Public Health England.https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/534174/Guidance_Candida__auris.pdf. Accessed on November 11th, 2016.</ref> The high rate of therapeutic failure noted in cases of ''Candida auris'' fungemia poses significant concerns.<ref name="pmidPMID 24357342" /> Misidentification of ''C.auris'' with related ''[[Candida]]'' species such as ''Candida haemulonii'' by commercially available biochemical-based tests poses a challenge.<ref name="cdc1" /> ''C. auris'' is recognized as a globally emerging fungal pathogen and it requires reproducible laboratory methods for identification and typing.<ref name="pmidPMID 26548511">{{cite journal| author=Prakash A, Sharma C, Singh A, Kumar Singh P, Kumar A, Hagen F et al.| title=Evidence of genotypic diversity among Candida auris isolates by multilocus sequence typing, matrix-assisted laser desorption ionization time-of-flight mass spectrometry and amplified fragment length polymorphism. | journal=Clin Microbiol Infect | year= 2016 | volume= 22 | issue= 3 | pages= 277.e1-9 | pmid=PMID 26548511 | doi=10.1016/j.cmi.2015.10.022 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26548511  }} </ref><ref name="pmidPMID 27777756">{{cite journal| author=Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A et al.| title=First hospital outbreak of the globally emerging Candida auris in a European hospital. | journal=Antimicrob Resist Infect Control | year= 2016 | volume= 5 | issue=  | pages= 35 | pmid=PMID 27777756 | doi=10.1186/s13756-016-0132-5 | pmc=5069812 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27777756  }} </ref> Institution of key infection prevention and control measures,<ref name="cdc2" /> correct identification and standardized antifungal susceptibility testing for optimal management strategies of patients with invasive infections can hardly be overemphasized.<ref name="cdc2" />
==Historical Perspective==
* ''C. auris'' was first described in 2009 after being isolated from the external ear canal discharge of a patient in Japan.<ref name="pmidPMID 27832049" />
* ''C. auris'' was incidentally found by molecular identification of bloodstream isolates of unidentified yeasts recovered in 1996, suggesting the paucity of isolation of ''C. auris'' may partly reflect the difficulty in identifying the specie.<ref name="pmid21715586">{{cite journal| author=Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH et al.| title=First three reported cases of nosocomial fungemia caused by Candida auris. | journal=J Clin Microbiol | year= 2011 | volume= 49 | issue= 9 | pages= 3139-42 | pmid=21715586 | doi=10.1128/JCM.00319-11 | pmc=3165631 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21715586  }} </ref>
* The occurrence of ''C. auris'' in nine countries on four continents since 2009 has been reported.<ref name="cdc1" />
* ''C. auris'' infections have most commonly been hospital-acquired and occurred several weeks into a patient’s hospital stay.<ref name="cdc1" />
* It has been documented to cause infections in patients of all ages.<ref name="cdc1" /><ref name="pmid21715586" /><ref name="pmidPMID 25989098">{{cite journal| author=Emara M, Ahmad S, Khan Z, Joseph L, Al-Obaid I, Purohit P et al.| title=Candida auris candidemia in Kuwait, 2014. | journal=Emerg Infect Dis | year= 2015 | volume= 21 | issue= 6 | pages= 1091-2 | pmid=PMID 25989098 | doi=10.3201/eid2106.150270 | pmc=4451886 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25989098  }} </ref>
 
== Causes ==
''Candida auris'' infection is caused by ''C. auris,'' a novel ascomycetous yeast species belonging to the genus ''[[Candida]],''<ref name="pmid19161556">{{cite journal| author=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=Microbiol Immunol | year= 2009 | volume= 53 | issue= 1 | pages= 41-4 | pmid=19161556 | doi=10.1111/j.1348-0421.2008.00083.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19161556  }} </ref>with high potential for nosocomial horizontal transmission.<ref name="pmidPMID 27777756" /><ref name="pmidPMID 27452195">{{cite journal| author=Calvo B, Melo AS, Perozo-Mena A, Hernandez M, Francisco EC, Hagen F et al.| title=First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia. | journal=J Infect | year= 2016 | volume= 73 | issue= 4 | pages= 369-74 | pmid=PMID 27452195 | doi=10.1016/j.jinf.2016.07.008 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27452195  }} </ref>
 
 
 
==Pathophysiology==
 
=== Pathogenesis ===
* ''C. auris'' cases have been identified from clinical sites such as wound swabs, urine samples, vascular devices tips, blood cultures as well as skin screening samples (including nose, oropharynx, axilla, groin and stool samples).<ref name="pmidPMID 27777756" />
* ''C. auris'' has been reported to cause bloodstream infections, wound infections, and [[otitis]].<ref name="cdc1" /><ref name="pmid21715586" />
* The occurrence of [[candidemia]] attributed to ''C. auris'' appears increasingly common.<ref name="pmidPMID 27777756" />
* Evidence of distinct geographic clustering of ''Candida auris'' isolates has been established.<ref name="pmidPMID 26548511" />
* ''C. auris'' has been isolated from the blood culture of a patient who was already on antifungals for ''C. albicans'' [[candidemia]].<ref name="pmid21715586" />
* The exact mode of transmission is unknown.<ref name="cdc1" /><ref name="cdc2" />
 
 
 
=== Genetics ===
* ''C. auris'' has a complex genome.<ref name="pmidPMID 26548511" />
* It is phylogenetically closely related to ''C. haemulonii.''<ref name="pmidPMID 26548511" />
* Detailed information regarding genotypes/clonal strains endemic to specific geographical locations is lacking.<ref name="pmidPMID 26548511" />
 
=== Microscopic Pathology ===
* ''C. auris'' cannot be distinguished from most other ''[[Candida]]'' species on microscopy.<ref name="cdc2" />
* It is a germ tube test negative budding yeast.<ref name="cdc2" />
* It has a pale purple/pink color on chromogenic agar.<ref name="cdc2" />
 
==Epidemiology and Demographics==
 
=== Age ===
* C. auris infection has been documented in both pediatric and adult population.<ref name="pmid21715586" /><ref name="cdc1" /><ref name="pmidPMID 25989098" />
 
=== Gender ===
* No known gender predilection
 
=== Race ===
* No known racial predilection.
 
===Geographical Distribution===
{| class="wikitable"
!Country/Region
!First Reported Case
!Adult/Pediatric Case
!Number of Reported Cases
|-
|Japan
|2009
|Adult
|
|-
|Kuwait<ref name="pmidPMID 25989098" />
|2014
|Adult
|
|-
|Venezuela<ref name="pmidPMID 27452195" />
|2012
|Adult and Pediatric
|18
|-
|South Korea<ref name="pmid21715586" />
|2009
|
|
|-
|
|
|
|
|-
|United States<ref name="pmidPMID 27832049" />
|2013
|
|7
|}
 
''C. auris'' was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan.<ref name="pmidPMID 27832049" /> Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom.<ref name="pmidPMID 27832049" /> Seven cases have been described in the US.<ref name="pmidPMID 27832049" />
 
Pediatric and adult cases of ''Candida auris'' fungemia have been documented.<ref name="cdc1" /><ref name="pmid21715586" /><ref name="pmidPMID 25989098" />
 
==Risk factors==
* Stay in the Intensive Care Unit is a major risk factor for ''C. auris'' infection.<ref name="pmidPMID 27777756" /><ref name="pmidPMID 26548511" />
* Patients who had a prolonged hospital stay.<ref name="cdc1" />
* Multiple invasive medical procedures.<ref name="pmidPMID 27452195" />
* Similar risk factors for infections with other ''[[Candida]]'' spp including diabetes mellitus, recent surgery, recent antibiotics, and presence of central venous catheters.<ref name="cdc1" />
* Co-infection with other ''[[Candida]]'' spp.<ref name="pmid21715586" /><ref name="cdc1" />
 
==  Screening ==
Screening is advised for patients coming from other affected hospitals / units in the UK and abroad.<ref name="cdc1" />
 
==Natural History, Complications, and Prognosis==
 
=== Natural History ===
* Colonization of patients has been reported from affected hospitals around the world.<ref name="cdc2" />
* Colonization with C. auris tends to persist and is difficult to eradicate.<ref name="cdc2" />
 
=== Complications ===
* Invasive wound infections.<ref name="pmidPMID 27832049" />
* Otitis.<ref name="cdc1" />
* Candidemia with high mortality.<ref name="pmidPMID 27832049" /><ref name="pmidPMID 27777756" />
 
=== Prognosis ===
* [[Candidemia]]  attributed to ''C auris'' is associated with mortality of up to 50 % in some countries.<ref name="pmidPMID 27777756" />
 
==Diagnosis==
 
=== History and Symptoms ===
 
=== Physical Examination ===
 
=== Laboratory Findings ===
''C. auris'', on microscopy, is indistinguishable from most other ''[[Candida]]'' species.<ref name="cdc2" /> It is a germ tube test negative budding yeast, however some strains can form rudimentary pseudohyphae on cornmeal agar. Most ''C. auris'' isolates are a pale purple or pink colour on the chromogenic agar (CHROMagar), in common with several other non-C. albicans species. Growth on this and other chromogenic agars (which may display a different colour) cannot be used as a primary identification method. Chromogenic agars are useful to identify mixed cultures including the presence of ''[[C. albicans]]''. If there is evidence of non-C. albicans on chromogenic agar, these should be sub-cultured on Sabouraud’s agar and identified according to local laboratory protocols.<ref name="cdc2" />
Currently available biochemical-based tests is highly unlikely to include C. auris in their database as it is a newly recognised species. Laboratories are advised to check the databases provided for their current methods. Commercially available biochemical-based tests, including API AUX 20C and VITEK-2 YST, used in many front line diagnostic laboratories can misidentify ''C. auris'' as ''Candida haemulonii'', ''Saccharomyces cerevisiae, Rhodotorula glutinis''.<ref name="cdc2" /> <ref name="pmidPMID 26548511" />Therefore, it is important that any ''[[Candida]]'' spp isolates associated with invasive infections and isolates from superficial sites in patients from high intensity settings and those transferred from an affected hospital should be analysed to species level. If ''Candida haemulonii'', ''Candida famata'', ''Candida sake'' or ''Saccharomyces cerevisiae'' are identified, it is pertinent to ensure that they are not ''C. auris''. This would involve either molecular sequencing of the D1/D2 domain or MALDI-TOF(matrix-assisted laser desorption ionization time-of-flight mass spectrometry) Biotyper analysis with ''C. auris'' either already present or added to the database.<ref name="cdc2" />
 
 
 
 
 
==Differentiating ''Candida auris'' from other ''[[non-Candida albicans]]'' species==
 
* Currently, reliable methods for speciation are molecular based methods such as PCR, AFLP(amplified fragment length polymorphism) fingerprinting, sequencing analysis, and MALDI-TOF biotyping.<ref name="cdc2" /><ref name="pmidPMID 27777756" />
 
==Treatment==
 
=== Medical Therapy ===
*Early identification of ''Candida'' species.<ref name="pmidPMID 27777756" />
* Candida auris isolates from north and south Indian hospitals, Japan and Korea were all found to be resistant to the antifungal medication fluconazole.<ref name="pmidPMID 24357342" />Some isolates were also noted to be resistant to antifungal medications such as flucytosine and voriconazole.<ref name="pmidPMID 24357342" />
* Antifungal susceptibility testing: There are no established minimum inhibitory concentration (MIC) breakpoints at present for ''C. auris''. Using breakpoints for other ''Candida'' spp, the Centers for Disease Control and Prevention (CDC) demonstrated that of the global outbreaks that they have been investigating, nearly all isolates are highly resistant to fluconazole. In their analysis, more than half of ''C. auris'' isolates were resistant to voriconazole, one- third were resistant to amphotericin B (MIC ≥2 mg/L), and a few were resistant to echinocandins. Some isolates have demonstrated elevated MICs to all three major antifungal classes, including azoles, echinocandins, and polyenes indicating that treatment options would be limited. Whole genome sequencing of the organism has found resistant determinants to a variety of antifungal agents.<ref name="cdc2" />
* First-line therapy is an echinocandin pending specific susceptibility testing which should be undertaken as soon as possible. However, there is evidence that resistance can evolve quite rapidly in this species, ongoing vigilance for evolving resistance is advised in patients who are found to be infected or colonised with ''C. auris''.<ref name="cdc2" />
* Evidence supporting combination therapy in invasive infections with ''C. auris''  is lacking and clinicians are advised to make decisions on a case by case basis.<ref name="cdc2" />
 
 
 
=== '''Primary Prevention''' ===
* isolation of colonized or infected patients with en suite facilities wherever possible.<ref name="cdc2" />
* Adherence to strict Infection Prevention and Control precautions, including hand hygiene using soap and water followed by alcohol hand rub, use of personal protective equipment in the form of gloves and aprons (or gowns if there is a high risk of soiling with blood or body fluids).<ref name="cdc2" />
* A chlorine releasing agent is currently recommended for cleaning of the environment at 1000 ppm of available chlorine.<ref name="cdc2" />
* A terminal clean should be undertaken once the patient has left the environment preferably using hydrogen peroxide vapour. All equipment should be cleaned in accordance with manufacturer’s instructions and where relevant, returned to the company for cleaning. Particular attention should be paid to cleaning of multiple-use equipment (such as  BP cuffs, thermometers, computers on wheels, ultra-sound machines) from the bed spaces of infected/colonized patient.<ref name="cdc2"/>
 
== References ==
{{reflist|2}}
{{SI}}

Latest revision as of 19:12, 17 November 2016

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