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

Candida auris overview|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] 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.[4] The precise mode of transmission within the healthcare facility is unknown.[3][4] 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.[3] C. auris is recognized as a globally emerging fungal pathogen.[5][6] Institution of key infection prevention and control measures[4] and, correct identification and standardized antifungal susceptibility testing for optimal management strategies of patients with invasive infections can hardly be overemphasized.[4]

Candida auris historical perspective|Historical Perspective

  • C. auris was first described in 2009 after being isolated from 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.[7]
  • The occurrence of C. auris in nine countries on four continents since 2009 has been reported.[3]
  • C. auris infections have most commonly been hospital-acquired and occurred several weeks into a patient’s hospital stay.[3]
  • It has been documented to cause infections in patients of all ages.[3][7][8]

Candida auris pathophysiology|Pathophysiology

  • High potential for nosocomial horizontal transmission.[6][9]
  • The exact mode of transmission is unknown.[3][4]

Candida auris infection|Infection

  • C. auris is a novel ascomycetous yeast species belonging to the genus Candida.[10]
  • It can cause invasive infections, and it is associated with high mortality.[2]
  • 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).[6]
  • C. auris has been reported to cause bloodstream infections, wound infections, and otitis.[3][7]
  • Stay in the Intensive Care Unit has been reported as a major risk factor for C. auris infection.[6]
  • Patients were found to have similar risk factors for infection with other Candida spp.[3]
  • The occurrence of candidemia attributed to C. auris appears increasingly common.[6]
  • Evidence of distinct geographic clustering of Candida auris isolates has been established.[5]

Candida auris differential diagnosis|Differentiating Candida auris from other Candida species

  • C. auris, on microscopy, is indistinguishable from most other Candida species, 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 Candida, 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 - albicans on chromogenic agar these should be sub-cultured on Sabouraud’s agar and identified according to local laboratory protocols.[4]
  • It is unlikely that any of the currently available biochemical-based tests will include C. auris in their database as it is a newly recognised species so laboratories are advised to check the databases provided for their current methods. According to published data, 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 or Rhodotorula glutinis (the latter species is pink on Sabouraud’s agar and is easily distinguished). 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, further work should be undertaken to ensure that they are not C. auris. This would involve either molecular sequencing of the D1/D2 domain or MALDI-TOF Biotyper analysis with C. auris either already present or added to the database.[4]

Candida auris epidemiology and demographics|Epidemiology and Demographics

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.[3][7][8]

Candida auris risk factors|Risk factors

  • Patients who had a prolonged hospital stay.[3]
  • Patients were found to have similar risk factors for infections with other Candida spp including diabetes mellitus, recent surgery, recent antibiotics, and presence of central venous catheters.[3]
  • Co-infection with other Candida spp.[3]
  • C. auris detection while the patient was being treated with antifungals have also been reported.[3]

Candida auris fungemia prognosis|Prognosis

  • Candidemia attributed to C auris is associated with mortality of up to 50 % in some countries.[6]

Diagnosis

  • Currently, reliable methods for speciation are molecular based methods such as PCR, AFLP fingerprinting, sequencing analysis, and MALDI-TOF biotyping.[6]

Treatment

  • Early identification of Candida species.[6]
  • 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.[4]
  • First-line therapy remains 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. There is currently no evidence or experience to support combination therapy in invasive infections with this organism and clinicians are advised to make decisions on a case by case basis.[4]

Prevention

  • isolation of colonised or infected patients with en suite facilities wherever possible.[4]
  • 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).[4]
  • A chlorine releasing agent is currently recommended for cleaning of the environment at 1000 ppm of available chlorine.[4]
  • 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.[4]

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. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 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 Centers for Disease Control and Prevention. https://www.cdc.gov/fungal/diseases/candidiasis/candida-auris-alert.html Accessed on November 11th, 2016.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 Public Health England.https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/534174/Guidance_Candida__auris.pdf. Accessed on November 11th, 2016.
  5. 5.0 5.1 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).
  6. 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 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).
  7. 7.0 7.1 7.2 7.3 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.
  8. 8.0 8.1 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. 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).
  10. 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.

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