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!Country/Region
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|Japan
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|Kuwait<ref name="pmidPMID 25989098" />
|Kuwait<ref name="pmidPMID 25989098" />
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|Venezuela<ref name="pmidPMID 27452195" />
|Venezuela<ref name="pmidPMID 27452195" />
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|United States<ref name="pmidPMID 27832049" />
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|Respiratory failure requiring high-dose steroids
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Revision as of 20:00, 15 November 2016


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Fatimo Biobaku M.B.B.S [2]

This page is describing the Candida auris infection. For more information on the microorganism click here.

Overview

Candida auris is a fungus, recently described as a rare cause of fungal infection with significant resistance to antifungal medications.[1] It was first described in the year 2009 in Japan,[2] and since then, reports of C. auris infection has been published from several countries.[2] However, retrospective testing of collected isolates show the earliest known infection with C. auris occurred in South Korea in 1996.[3][4] 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.[5] 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.[5] The precise mode of transmission within the healthcare facility is unknown.[6][3] The high rate of therapeutic failure noted in cases of Candida auris fungemia poses significant concerns.[1] Misidentification of C.auris with related Candida species such as Candida haemulonii by commercially available biochemical-based tests poses a challenge.[6] C. auris is recognized as a globally emerging fungal pathogen and it requires reproducible laboratory methods for identification and typing.[7][5] Institution of key infection prevention and control measures,[3] correct identification and standardized antifungal susceptibility testing for optimal management strategies of patients with invasive infections can hardly be overemphasized.[3]

Historical Perspective

  • C. auris was first described in 2009 after being isolated from the external ear canal discharge of a patient in Japan.[2]
  • 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.[4]
  • The occurrence of C. auris in nine countries on four continents since 2009 has been reported.[6]
  • C. auris infections have most commonly been hospital-acquired and occurred several weeks into a patient’s hospital stay.[6]
  • It has been documented to cause infections in patients of all ages.[6][4][8]

Causes

Candida auris infection is caused by C. auris, a novel ascomycetous yeast species belonging to the genus Candida,[9]with high potential for nosocomial horizontal transmission.[5][10]


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).[5]
  • C. auris has been reported to cause bloodstream infections, wound infections, and otitis.[6][4]
  • The occurrence of candidemia attributed to C. auris appears increasingly common.[5]
  • Evidence of distinct geographic clustering of Candida auris isolates has been established.[7]
  • C. auris has been isolated from the blood culture of a patient who was already on antifungals for C. albicans candidemia.[4]
  • The exact mode of transmission is unknown.[6][3]


Genetics

  • C. auris has a complex genome.[7]
  • It is phylogenetically closely related to C. haemulonii.[7]
  • Detailed information regarding genotypes/clonal strains endemic to specific geographical locations is lacking.[7]

Microscopic Pathology

  • C. auris cannot be distinguished from most other Candida species on microscopy.[3]
  • It is a germ tube test negative budding yeast.[3]
  • It has a pale purple/pink color on chromogenic agar.[3]

Epidemiology and Demographics

Age

  • C. auris infection has been documented in both pediatric and adult population.[4][6][8]

Gender

  • No known gender predilection

Race

  • No known racial predilection.

Geographical Distribution

Country/Region Month/Year of Isolation Site of Isolation Underlying Medical Condition(s)
Japan 2009 Ear
Kuwait[8] 2014
Venezuela[10] 2012
South Korea[4] 2009
United States[2] May/2013 Blood Respiratory failure requiring high-dose steroids

C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan.[2] 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.[2] Seven cases have been described in the US.[2]

Pediatric and adult cases of Candida auris fungemia have been documented.[6][4][8]

Risk factors

  • Stay in the Intensive Care Unit is a major risk factor for C. auris infection.[5][7]
  • Patients who had a prolonged hospital stay.[6]
  • Multiple invasive medical procedures.[10]
  • Similar risk factors for infections with other Candida spp including diabetes mellitus, recent surgery, recent antibiotics, presence of central venous catheters.[6]
  • Serious underlying medical conditions such as hematologic malignancies, respiratory failure requiring high dose steroids, short gut syndrome requiring total parenteral nutrition, paraplegia with a chronic urinary catheter, etc.[2]
  • Co-infection with other Candida spp.[4][6]

Screening

Screening is advised for patients coming from other affected hospitals / units in the UK and abroad.[6]

Natural History, Complications, and Prognosis

Natural History

  • Colonization of patients has been reported from affected hospitals around the world.[3]
  • Colonization with C. auris tends to persist and is difficult to eradicate.[3]
  • Recurrence of C. auris candedemia three to four months after an initial episode has been reported in at least two patients.[2]

Complications

  • Invasive wound infections.[2]
  • Otitis.[6]
  • Candidemia with high mortality.[2][5]

Prognosis

  • Candidemia attributed to C auris is associated with mortality of up to 50 % in some countries.[5]

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

C. auris, on microscopy, is indistinguishable from most other Candida species.[3] 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.[3] 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.[3] [7]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.[3]


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.[3][5]

Treatment

Medical Therapy

  • Early identification of Candida species.[5]
  • Candida auris isolates from north and south Indian hospitals, Japan and Korea were all found to be resistant to the antifungal medication fluconazole.[1]Some isolates were also noted to be resistant to antifungal medications such as flucytosine and voriconazole.[1]
  • 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.[3]
  • 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.[3]
  • 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.[3]


Primary Prevention

  • isolation of colonized or infected patients with en suite facilities wherever possible.[3]
  • 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).[3]
  • A chlorine releasing agent is currently recommended for cleaning of the environment at 1000 ppm of available chlorine.[3]
  • 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.[3]

References

  1. 1.0 1.1 1.2 1.3 Chowdhary A, Anil Kumar V, Sharma C, Prakash A, Agarwal K, Babu R; et al. (2014). "Multidrug-resistant endemic clonal strain of Candida auris in India". Eur J Clin Microbiol Infect Dis. 33 (6): 919–26. doi:10.1007/s10096-013-2027-1. PMID 24357342 PMID 24357342 Check |pmid= value (help).
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Vallabhaneni S, Kallen A, Tsay S, Chow N, Welsh R, Kerins J; et al. (2016). "Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016". MMWR Morb Mortal Wkly Rep. 65 (44): 1234–1237. doi:10.15585/mmwr.mm6544e1. PMID 27832049 PMID 27832049 Check |pmid= value (help).
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 3.17 3.18 3.19 3.20 3.21 Public Health England.https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/534174/Guidance_Candida__auris.pdf. Accessed on November 11th, 2016.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Lee WG, Shin JH, Uh Y, Kang MG, Kim SH, Park KH; et al. (2011). "First three reported cases of nosocomial fungemia caused by Candida auris". J Clin Microbiol. 49 (9): 3139–42. doi:10.1128/JCM.00319-11. PMC 3165631. PMID 21715586.
  5. 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 Schelenz S, Hagen F, Rhodes JL, Abdolrasouli A, Chowdhary A, Hall A; et al. (2016). "First hospital outbreak of the globally emerging Candida auris in a European hospital". Antimicrob Resist Infect Control. 5: 35. doi:10.1186/s13756-016-0132-5. PMC 5069812. PMID 27777756 PMID 27777756 Check |pmid= value (help).
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 Centers for Disease Control and Prevention. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html Accessed on November 11th, 2016.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 7.6 Prakash A, Sharma C, Singh A, Kumar Singh P, Kumar A, Hagen F; et al. (2016). "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". Clin Microbiol Infect. 22 (3): 277.e1–9. doi:10.1016/j.cmi.2015.10.022. PMID 26548511 PMID 26548511 Check |pmid= value (help).
  8. 8.0 8.1 8.2 8.3 Emara M, Ahmad S, Khan Z, Joseph L, Al-Obaid I, Purohit P; et al. (2015). "Candida auris candidemia in Kuwait, 2014". Emerg Infect Dis. 21 (6): 1091–2. doi:10.3201/eid2106.150270. PMC 4451886. PMID 25989098 PMID 25989098 Check |pmid= value (help).
  9. Satoh K, Makimura K, Hasumi Y, Nishiyama Y, Uchida K, Yamaguchi H (2009). "Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital". Microbiol Immunol. 53 (1): 41–4. doi:10.1111/j.1348-0421.2008.00083.x. PMID 19161556.
  10. 10.0 10.1 10.2 Calvo B, Melo AS, Perozo-Mena A, Hernandez M, Francisco EC, Hagen F; et al. (2016). "First report of Candida auris in America: Clinical and microbiological aspects of 18 episodes of candidemia". J Infect. 73 (4): 369–74. doi:10.1016/j.jinf.2016.07.008. PMID 27452195 PMID 27452195 Check |pmid= value (help).

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