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Candida auris: An emerging multidrug-resistant pathogen

Open AccessPublished:September 06, 2017DOI:https://doi.org/10.1016/j.ijid.2017.08.017

      Abstract

      Candida aurisis an emerging multidrug-resistant pathogen that can be difficult to identify using traditional biochemical methods. C. auris is capable of causing invasive fungal infections, particularly among hospitalized patients with significant medical comorbidities. Echinocandins are the empiric drugs of choice for C. auris, although not all isolates are susceptible and resistance may develop on therapy. Nosocomial C. auris outbreaks have been reported in a number of countries and aggressive infection control measures are paramount to stopping transmission.

      Keywords

      Introduction

      Candida auris was first identified from samples of external ear drainage from one Japanese patient (
      • Satoh Kazuo
      • Makimura Koichi
      • Hasumi Yayoi
      • Nishiyama Yayoi
      • Uchida Katsuhisa
      • Yamaguchi Hideyo
      Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital.
      ) and 15 Korean patients in 2009 (
      • Kim Mi-Na
      • Shin Jong Hee
      • Sung Heungsup
      • Lee Kyungwon
      • Kim Eui-Chong
      • Ryoo Namhee
      • et al.
      Candida haemulonii and closely related Species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features.
      ). This organism can be challenging to identify using standard microbiologic techniques and frequently exhibits multidrug-resistance. In the eight years since these initial cases, C. auris has become an emerging global health threat, implicated in a host of invasive infections and outbreaks in healthcare facilities. To date, cases have now been identified in India (
      • Sarma S.
      • Kumar N.
      • Sharma S.
      • Govil D.
      • Ali T.
      • Mehta Y.
      • et al.
      Candidemia caused by amphotericin B and fluconazole resistant Candida auris.
      ,
      • Chowdhary Anuradha
      • Sharma Cheshta
      • Duggal Shalini
      • Agarwal Kshitij
      • Prakash Anupam
      • Singh Pradeep Kumar
      • et al.
      New clonal strain of Candida auris, Delhi, India.
      ), South Africa (
      • Magobo Rindidzani
      • Corcoran Craig
      • Seetharam Sharona
      • Govender Nelesh
      Candida auris–associated candidemia, South Africa.
      ), Kuwait (
      • Emara Maha
      • Ahmad Suhail
      • Khan Ziauddin
      • Joseph Leena
      • Al-Obaid Ina’m
      • Purohit Prashant
      • et al.
      Candida auris candidemia in Kuwait, 2014.
      ), the United Kingdom (
      • Schelenz Silke
      • Hagen Ferry
      • Rhodes Johanna L.
      • Abdolrasouli Alireza
      • Chowdhary Anuradha
      • Hall Anne
      • et al.
      First hospital outbreak of the globally emerging Candida auris in a European hospital.
      ), Venezuela (
      • Calvo Belinda
      • Melo Analy S.A.
      • Perozo-Mena Armindo
      • Hernandez Martin
      • Francisco Elaine Cristina
      • Hagen Ferry
      • et al.
      First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia.
      ), Brazil (
      • Prakash A.
      • Sharma C.
      • Singh A.
      • Kumar Singh P.
      • Kumar A.
      • Hagen F.
      • et al.
      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.
      ), the United States (
      • Vallabhaneni S.
      • Kallen A.
      • Tsay S.
      • Chow N.
      • Welsh R.
      • Kerins J.
      • 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.
      ), Colombia (
      • Morales-López Soraya
      • Parra-Giraldo Claudia
      • Ceballos-Garzon Andres
      • Martinez Heidys
      • Rodriguez Gerson
      • Alvarez-Moreno Carlos
      • et al.
      Invasive infections with multidrug-resistant yeast Candida auris, Colombia.
      ), Pakistan (
      • Lockhart Shawn R.
      • Etienne Kizee A.
      • Vallabhaneni Snigdha
      • Farooqi Joveria
      • Chowdhary Anuradha
      • Govender Nelesh P.
      • et al.
      Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses.
      ), Spain (
      • Ruiz Gaitán Alba Cecilia
      • Moret Ana
      • López Hontangas José Luis
      • Molina José Miguel
      • Aleixandre López Ana Isabel
      • Cabezas Alicia Hernández
      • et al.
      Nosocomial fungemia by Candida auris: first four reported cases in continental Europe.
      ), Germany (
      • European Centre for Disease Prevention and Control
      Candida auris in healthcare settings – Europe.
      ), Israel (
      • Ben-Ami Ronen
      • Berman Judith
      • Novikov Ana
      • Bash Edna
      • Shachor-Meyouhas Yael
      • Zakin Shiri
      • et al.
      Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel.
      ), Norway (
      • European Centre for Disease Prevention and Control
      Candida auris in healthcare settings – Europe.
      ), and Oman (
      • Al-Siyabi Turkiya
      • Al Busaidi Ibrahim
      • Balkhair Abdullah
      • Al-Muharrmi Zakariya
      • Al-Salti Maya
      • Al’Adawi Badriya
      First report of Candida auris in Oman: clinical and microbiological description of five candidemia cases.
      ). This review will detail the microbiology, clinical features, therapeutic options, and infection control measures relevant to C. auris infection.

      Microbiology and diagnosis

      C. auris is phylogenetically related to Candida haemulonii and Candida ruelliae (
      • Satoh Kazuo
      • Makimura Koichi
      • Hasumi Yayoi
      • Nishiyama Yayoi
      • Uchida Katsuhisa
      • Yamaguchi Hideyo
      Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital.
      ). Four distinct clades have been identified from separate geographic origins, suggesting a recent and nearly simultaneous emergence of different clonal populations (
      • Lockhart Shawn R.
      • Etienne Kizee A.
      • Vallabhaneni Snigdha
      • Farooqi Joveria
      • Chowdhary Anuradha
      • Govender Nelesh P.
      • et al.
      Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses.
      ). C. auris grows readily at 37–42 °C and forms light pink colonies on chromogenic media (
      • Chowdhary A.
      • Anil Kumar V.
      • Sharma C.
      • Prakash A.
      • Agarwal K.
      • Babu R.
      • et al.
      Multidrug-resistant endemic clonal strain of Candida auris in India.
      ,
      • Kathuria Shallu
      • Singh Pradeep K.
      • Sharma Cheshta
      • Prakash Anupam
      • Masih Aradhana
      • Kumar Anil
      • et al.
      Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by vitek 2, CLSI broth microdilution, and etest method.
      ). Unlike C. haemulonii, C. auris does not form pseudohyphae. Only some C. auris strains produce the virulence factors phospholipase and proteinase, which may account for the variability in pathogenicity demonstrated in a murine model (
      • Borman Andrew M.
      • Szekely Adrien
      • Johnson Elizabeth M.
      Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida Species.
      ,
      • Larkin Emily
      • Hager Christopher
      • Chandra Jyotsna
      • Mukherjee Pranab K.
      • Retuerto Mauricio
      • Salem Iman
      • et al.
      The emerging pathogen Candida auris: growth phenotype, virulence factors, activity of antifungals, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation.
      ). C. auris is capable of forming biofilms (
      • Oh Bong Joon
      • Shin Jong Hee
      • Kim Mi-Na
      • Sung Heungsup
      • Lee Kyungwon
      • Joo Min Young
      • et al.
      Biofilm formation and genotyping of Candida haemulonii, Candida pseudohaemulonii, and a proposed new species (Candida auris) isolates from Korea.
      ) and adhering to catheter material, although not to the same degree as Candida albicans (
      • Larkin Emily
      • Hager Christopher
      • Chandra Jyotsna
      • Mukherjee Pranab K.
      • Retuerto Mauricio
      • Salem Iman
      • et al.
      The emerging pathogen Candida auris: growth phenotype, virulence factors, activity of antifungals, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation.
      ).
      Traditional biochemical methods of identification commonly misdiagnose C. auris as other yeast. The United States Centers for Disease Control and Prevention (CDC) recommends further testing for C. auris whenever C. haemulonii is identified or in a number of other scenarios depending on the organism reported and the method of identification (Table 1). Accurate identification can be performed with VITEK MS and Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) devices using their “research use only” databases. Molecular sequencing of the D1–D2 domain of the 28s rDNA can also identify C. auris (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ). For laboratories without the capability to perform these tests, Kumar et al. propose a low-cost alternative that can accurately distinguish C. auris from C. haemulonii using CHROMagar medium supplemented with Pal’s medium (
      • Kumar Anil
      • Sachu Arun
      • Mohan Karthika
      • Vinod Vivek
      • Dinesh Kavitha
      • Karim Shamsul
      Simple low cost differentiation of Candida auris from Candida haemulonii complex using CHROMagar Candida medium supplemented with Pal’s medium.
      ).
      Table 1When to suspect Candida auris based on the organism presumptively identified and the method of identification (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ).
      Source: US Centers for Disease Control and Prevention.
      Organism reportedMethod
      Candida haemuloniiAny
      Candida spp.Any validated identification method
      Rhodotorula glutinisAPI 20C if red color is not present
      Candida sakeAPI 20C
      Candida catenulataBD Phoenix
      Candida catenulataMicroScan
      Candida famataMicroScan
      Candida guilliermondiiMicroScan
      Candida lusitaniaeMicroScan

      Clinical features

      Risk factors for C. auris infection appear to be similar to infections from Candida in general. These include immunosuppressed state, significant medical comorbidities, central venous catheters, urinary catheters, recent surgery, parenteral nutrition, exposure to broad spectrum antimicrobials, intensive care unit admission, and residence in a high-acuity skilled nursing facility (
      • Vallabhaneni S.
      • Kallen A.
      • Tsay S.
      • Chow N.
      • Welsh R.
      • Kerins J.
      • 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.
      ,
      • Sarma Smita
      • Upadhyay Shalini
      Current perspective on emergence, diagnosis and drug resistance in Candida auris.
      ). In a case-control study investigating risk factors for C. auris fungemia compared to bloodstream infection from other Candida species in Indian ICUs, those with C. auris fungemia were more likely to have had longer antecedent hospitalizations, underlying respiratory conditions, vascular surgery, prior antifungal exposure, and low APACHE II scores. Patients with C. auris fungemia in this study were also more frequently from public-sector ICUs from the north of India (
      • Rudramurthy Shivaprakash M.
      • Chakrabarti Arunaloke
      • Paul Raees A.
      • Sood Prashant
      • Kaur Harsimran
      • Capoor Malini R.
      • et al.
      Candida auris candidaemia in Indian ICUs: analysis of risk factors.
      ).
      C. auris has been recovered in samples from blood, catheter tips, cerebrospinal fluid, bone, ear discharge, pancreatic fluid, pericardial fluid, peritoneal fluid, pleural fluid, respiratory secretions (including sputum and bronchoalveolar lavage), skin and soft tissue samples (both tissue and swab cultures), urine, and vaginal secretions. Clinically, it has been implicated as a causative agent in fungemia, ventriculitis, osteomyelitis, malignant otitis (including otomastoiditis), complicated intra-abdominal infections, pericarditis, complicated pleural effusions, and vulvovaginitis (
      • Satoh Kazuo
      • Makimura Koichi
      • Hasumi Yayoi
      • Nishiyama Yayoi
      • Uchida Katsuhisa
      • Yamaguchi Hideyo
      Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital.
      ,
      • Kim Mi-Na
      • Shin Jong Hee
      • Sung Heungsup
      • Lee Kyungwon
      • Kim Eui-Chong
      • Ryoo Namhee
      • et al.
      Candida haemulonii and closely related Species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features.
      ,
      • Sarma S.
      • Kumar N.
      • Sharma S.
      • Govil D.
      • Ali T.
      • Mehta Y.
      • et al.
      Candidemia caused by amphotericin B and fluconazole resistant Candida auris.
      ,
      • Magobo Rindidzani
      • Corcoran Craig
      • Seetharam Sharona
      • Govender Nelesh
      Candida auris–associated candidemia, South Africa.
      ,
      • Emara Maha
      • Ahmad Suhail
      • Khan Ziauddin
      • Joseph Leena
      • Al-Obaid Ina’m
      • Purohit Prashant
      • et al.
      Candida auris candidemia in Kuwait, 2014.
      ,
      • Schelenz Silke
      • Hagen Ferry
      • Rhodes Johanna L.
      • Abdolrasouli Alireza
      • Chowdhary Anuradha
      • Hall Anne
      • et al.
      First hospital outbreak of the globally emerging Candida auris in a European hospital.
      ,
      • Calvo Belinda
      • Melo Analy S.A.
      • Perozo-Mena Armindo
      • Hernandez Martin
      • Francisco Elaine Cristina
      • Hagen Ferry
      • et al.
      First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia.
      ,
      • Vallabhaneni S.
      • Kallen A.
      • Tsay S.
      • Chow N.
      • Welsh R.
      • Kerins J.
      • 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.
      ,
      • Morales-López Soraya
      • Parra-Giraldo Claudia
      • Ceballos-Garzon Andres
      • Martinez Heidys
      • Rodriguez Gerson
      • Alvarez-Moreno Carlos
      • et al.
      Invasive infections with multidrug-resistant yeast Candida auris, Colombia.
      ,
      • Lockhart Shawn R.
      • Etienne Kizee A.
      • Vallabhaneni Snigdha
      • Farooqi Joveria
      • Chowdhary Anuradha
      • Govender Nelesh P.
      • et al.
      Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses.
      ,
      • Ruiz Gaitán Alba Cecilia
      • Moret Ana
      • López Hontangas José Luis
      • Molina José Miguel
      • Aleixandre López Ana Isabel
      • Cabezas Alicia Hernández
      • et al.
      Nosocomial fungemia by Candida auris: first four reported cases in continental Europe.
      ,
      • Ben-Ami Ronen
      • Berman Judith
      • Novikov Ana
      • Bash Edna
      • Shachor-Meyouhas Yael
      • Zakin Shiri
      • et al.
      Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel.
      ,
      • Al-Siyabi Turkiya
      • Al Busaidi Ibrahim
      • Balkhair Abdullah
      • Al-Muharrmi Zakariya
      • Al-Salti Maya
      • Al’Adawi Badriya
      First report of Candida auris in Oman: clinical and microbiological description of five candidemia cases.
      ,
      • Borman Andrew M.
      • Szekely Adrien
      • Johnson Elizabeth M.
      Comparative pathogenicity of United Kingdom isolates of the emerging pathogen Candida auris and other key pathogenic Candida Species.
      ,
      • Lee Wee Gyo
      • Shin Jong Hee
      • Uh Young
      • Kang Min Gu
      • Kim Soo Hyun
      • Park Kyung Hwa
      • et al.
      First three reported cases of nosocomial fungemia caused by Candida auris.
      ,
      • Khillan Vikas
      • Rathore Neha
      • Kathuria Shallu
      • Chowdhary Anuradha
      A rare case of breakthrough fungal pericarditis due to fluconazole-resistant Candida auris in a patient with chronic liver disease.
      ,
      • Choi Hyoung I.
      • An Jin
      • Hwang Jae Joon
      • Moon Soo-youn
      • Son Jun Seong
      Otomastoiditis caused by Candida auris: case report and literature review.
      ,
      • Chowdhary Anuradha
      • Sharma Cheshta
      • Meis Jacques F.
      Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally.
      ,
      • Tsay Sharon
      • Welsh Rory
      • Adams Eleanor
      • Chow Nancy
      • Gade Lalitha
      • Berkow Elizabeth
      • et al.
      Notes from the field: ongoing transmission of Candida auris in health care facilities — United States, June 2016–May 2017.
      ). Much like other Candida species, there is uncertainty about the ability of C. auris to cause true respiratory, urinary, and skin and soft tissue infections despite being isolated from such samples.
      While one study reported no C. auris attributable deaths among nine patients with fungemia, crude mortality rates for C. auris fungemia have otherwise ranged from 28 to 66% across a wide range of healthcare settings and patient populations (
      • Chowdhary Anuradha
      • Sharma Cheshta
      • Duggal Shalini
      • Agarwal Kshitij
      • Prakash Anupam
      • Singh Pradeep Kumar
      • et al.
      New clonal strain of Candida auris, Delhi, India.
      ,
      • Calvo Belinda
      • Melo Analy S.A.
      • Perozo-Mena Armindo
      • Hernandez Martin
      • Francisco Elaine Cristina
      • Hagen Ferry
      • et al.
      First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia.
      ,
      • Vallabhaneni S.
      • Kallen A.
      • Tsay S.
      • Chow N.
      • Welsh R.
      • Kerins J.
      • 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.
      ,
      • Morales-López Soraya
      • Parra-Giraldo Claudia
      • Ceballos-Garzon Andres
      • Martinez Heidys
      • Rodriguez Gerson
      • Alvarez-Moreno Carlos
      • et al.
      Invasive infections with multidrug-resistant yeast Candida auris, Colombia.
      ,
      • Lockhart Shawn R.
      • Etienne Kizee A.
      • Vallabhaneni Snigdha
      • Farooqi Joveria
      • Chowdhary Anuradha
      • Govender Nelesh P.
      • et al.
      Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses.
      ,
      • Al-Siyabi Turkiya
      • Al Busaidi Ibrahim
      • Balkhair Abdullah
      • Al-Muharrmi Zakariya
      • Al-Salti Maya
      • Al’Adawi Badriya
      First report of Candida auris in Oman: clinical and microbiological description of five candidemia cases.
      ,
      • Chowdhary A.
      • Anil Kumar V.
      • Sharma C.
      • Prakash A.
      • Agarwal K.
      • Babu R.
      • et al.
      Multidrug-resistant endemic clonal strain of Candida auris in India.
      ,
      • Rudramurthy Shivaprakash M.
      • Chakrabarti Arunaloke
      • Paul Raees A.
      • Sood Prashant
      • Kaur Harsimran
      • Capoor Malini R.
      • et al.
      Candida auris candidaemia in Indian ICUs: analysis of risk factors.
      ,
      • Lee Wee Gyo
      • Shin Jong Hee
      • Uh Young
      • Kang Min Gu
      • Kim Soo Hyun
      • Park Kyung Hwa
      • et al.
      First three reported cases of nosocomial fungemia caused by Candida auris.
      ).

      Antifungal therapies

      Source control measures, including removal of indwelling catheters, are likely as important to the successful treatment of invasive C. auris infections as they are to other forms of invasive candidiasis. Regarding antifungal therapy, there are no Clinical and Laboratory Standards Institute (CLSI) or European Committee for Antimicrobial Susceptibility Testing (EUCAST) defined breakpoints for C. auris susceptibility. CDC recommends that all C. auris isolates undergo susceptibility testing and provides guidance for MIC breakpoints based on related Candida species and expert opinion (Table 2) (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ). Fluconazole (tentative MIC breakpoint ≥32) is associated with high minimum inhibitory concentrations (MICs) and is likely almost always resistant. Susceptibility testing from four studies involving between 54 and 123 clinical isolates revealed MIC50 results between 64 and 128 mg/L and MIC90 results between 64 and 256 mg/L by CLSI microbroth dilution. Echinocandins (tentative MIC breakpoint ≥4 for anidulafungin and micafungin, ≥2 for caspofungin) appear to be most active in these studies with favorable results for anidulafungin (MIC50 range 0.125–0.5, MIC90 range 0.5–1), caspofungin (MIC50 0.25–0.5, MIC90 1), and micafungin (MIC50 0.125–0.25, MIC90 0.25–2). Amphotericin B (tentative MIC breakpoint ≥2) susceptibility testing exhibits a wider range of MIC results (MIC50 0.5–1, MIC90 2–4) and is likely less reliable as empiric therapy (
      • Prakash A.
      • Sharma C.
      • Singh A.
      • Kumar Singh P.
      • Kumar A.
      • Hagen F.
      • et al.
      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.
      ,
      • Lockhart Shawn R.
      • Etienne Kizee A.
      • Vallabhaneni Snigdha
      • Farooqi Joveria
      • Chowdhary Anuradha
      • Govender Nelesh P.
      • et al.
      Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses.
      ,
      • Kathuria Shallu
      • Singh Pradeep K.
      • Sharma Cheshta
      • Prakash Anupam
      • Masih Aradhana
      • Kumar Anil
      • et al.
      Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by vitek 2, CLSI broth microdilution, and etest method.
      ,
      • Arendrup M.C.
      • Prakash Anupam
      • Meletiadis Joseph
      • Sharma Cheshta
      • Chowdhary Anuradha
      Comparison of EUCAST and CLSI Reference microdilution MICs of eight antifungal compounds for Candida auris and associated tentative epidemiological cutoff values.
      ). Regarding second generation triazole susceptibility, fluconazole susceptibility can be used as a surrogate although fluconazole-resistant isolates may occasionally respond to other triazole antifungals (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ). In comparison to CLSI microbroth dilution, similar MIC50 and MIC90 results can likely be obtained by the EUCAST method (
      • Arendrup M.C.
      • Prakash Anupam
      • Meletiadis Joseph
      • Sharma Cheshta
      • Chowdhary Anuradha
      Comparison of EUCAST and CLSI Reference microdilution MICs of eight antifungal compounds for Candida auris and associated tentative epidemiological cutoff values.
      ), although caution should be used when interpreting Etest and Vitek antifungal susceptibility testing results (
      • Kathuria Shallu
      • Singh Pradeep K.
      • Sharma Cheshta
      • Prakash Anupam
      • Masih Aradhana
      • Kumar Anil
      • et al.
      Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by vitek 2, CLSI broth microdilution, and etest method.
      ).
      Table 2Tentative MIC (mg/L) breakpoints for Candida auris susceptibility (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ) and published MIC ranges by CLSI microbroth dilution (
      • Prakash A.
      • Sharma C.
      • Singh A.
      • Kumar Singh P.
      • Kumar A.
      • Hagen F.
      • et al.
      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.
      ,
      • Lockhart Shawn R.
      • Etienne Kizee A.
      • Vallabhaneni Snigdha
      • Farooqi Joveria
      • Chowdhary Anuradha
      • Govender Nelesh P.
      • et al.
      Simultaneous emergence of multidrug-resistant Candida auris on 3 continents confirmed by whole-genome sequencing and epidemiological analyses.
      ,
      • Kathuria Shallu
      • Singh Pradeep K.
      • Sharma Cheshta
      • Prakash Anupam
      • Masih Aradhana
      • Kumar Anil
      • et al.
      Multidrug-resistant Candida auris misidentified as Candida haemulonii: characterization by matrix-assisted laser desorption ionization–time of flight mass spectrometry and DNA sequencing and its antifungal susceptibility profile variability by vitek 2, CLSI broth microdilution, and etest method.
      ,
      • Arendrup M.C.
      • Prakash Anupam
      • Meletiadis Joseph
      • Sharma Cheshta
      • Chowdhary Anuradha
      Comparison of EUCAST and CLSI Reference microdilution MICs of eight antifungal compounds for Candida auris and associated tentative epidemiological cutoff values.
      ).
      Antifungal drugTentative MIC breakpointPublished MIC50 rangePublished MIC90 range
      Fluconazole≥3264–12864–256
      Voriconazole
      Also applies to other second generation triazole antifungals.
      N/A
      Consider using fluconazole susceptibility as a surrogate, although fluconazole-resistant isolates may occasionally respond to other triazole antifungals.
      0.5–24–8
      Amphotericin B≥20.5–12–4
      Anidulafungin≥40.125–0.50.5–1
      Caspofungin≥20.25–0.51
      Micafungin≥40.125–0.250.25–2
      a Also applies to other second generation triazole antifungals.
      b Consider using fluconazole susceptibility as a surrogate, although fluconazole-resistant isolates may occasionally respond to other triazole antifungals.
      Based on these results, echinocandins are the empiric drugs of choice for C.auris infections in adults and children over the age of 2 months. Amphotericin B–while less reliable–should be considered for patients not responding to echinocandin therapy, depending on MIC results. A mouse model testing antifungal therapy on nine strains of C. auris suggested that micafungin may be particularly fungicidal and more active than tentative MIC breakpoints may suggest (
      • Lepak Alexander J.
      • Zhao Miao
      • Berkow Elizabeth L.
      • Lockhart Shawn R.
      • Andes David R.
      Pharmacodynamic optimization for treatment of invasive Candida auris infection.
      ), however further clinical studies in humans are needed. It is important to note that resistance may develop on therapy and close clinical follow-up and potentially repeat MIC testing may be indicated for patients who are responding poorly to antifungal therapy.
      Much like colonization with other multidrug-resistant species, CDC does not recommend systemic antifungal therapy for patients who are colonized with C. auris (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ).

      Infection control

      C. auris can cause widespread and persistent contamination of environmental surfaces within healthcare facilities and has been associated with both intra-hospital and inter-hospital transmission of clonal strains in multiple countries (
      • Kim Mi-Na
      • Shin Jong Hee
      • Sung Heungsup
      • Lee Kyungwon
      • Kim Eui-Chong
      • Ryoo Namhee
      • et al.
      Candida haemulonii and closely related Species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features.
      ,
      • Chowdhary Anuradha
      • Sharma Cheshta
      • Duggal Shalini
      • Agarwal Kshitij
      • Prakash Anupam
      • Singh Pradeep Kumar
      • et al.
      New clonal strain of Candida auris, Delhi, India.
      ,
      • Schelenz Silke
      • Hagen Ferry
      • Rhodes Johanna L.
      • Abdolrasouli Alireza
      • Chowdhary Anuradha
      • Hall Anne
      • et al.
      First hospital outbreak of the globally emerging Candida auris in a European hospital.
      ,
      • Calvo Belinda
      • Melo Analy S.A.
      • Perozo-Mena Armindo
      • Hernandez Martin
      • Francisco Elaine Cristina
      • Hagen Ferry
      • et al.
      First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia.
      ,
      • Morales-López Soraya
      • Parra-Giraldo Claudia
      • Ceballos-Garzon Andres
      • Martinez Heidys
      • Rodriguez Gerson
      • Alvarez-Moreno Carlos
      • et al.
      Invasive infections with multidrug-resistant yeast Candida auris, Colombia.
      ,
      • European Centre for Disease Prevention and Control
      Candida auris in healthcare settings – Europe.
      ,
      • Ben-Ami Ronen
      • Berman Judith
      • Novikov Ana
      • Bash Edna
      • Shachor-Meyouhas Yael
      • Zakin Shiri
      • et al.
      Multidrug-resistant Candida haemulonii and C. auris, Tel Aviv, Israel.
      ,
      • Tsay Sharon
      • Welsh Rory
      • Adams Eleanor
      • Chow Nancy
      • Gade Lalitha
      • Berkow Elizabeth
      • et al.
      Notes from the field: ongoing transmission of Candida auris in health care facilities — United States, June 2016–May 2017.
      ,
      • Piedrahita Christina T.
      • Cadnum Jennifer L.
      • Jencson Annette L.
      • Shaikh Aaron A.
      • Ghannoum Mahmoud A.
      • Donskey Curtis J.
      Environmental surfaces in healthcare facilities are a potential source for transmission of Candida auris and other Candida species.
      ). The largest reported outbreaks to date were in a cardio-thoracic center in the United Kingdom (22 patients infected and an additional 28 patients colonized) (
      • Schelenz Silke
      • Hagen Ferry
      • Rhodes Johanna L.
      • Abdolrasouli Alireza
      • Chowdhary Anuradha
      • Hall Anne
      • et al.
      First hospital outbreak of the globally emerging Candida auris in a European hospital.
      ) and a surgical intensive care unit in Spain (33 cases of C. auris fungemia) (
      • European Centre for Disease Prevention and Control
      Candida auris in healthcare settings – Europe.
      ). From 77 clinical cases in the United States, CDC used groin and axilla swabs to screen an additional 390 close contacts (mainly patients on the same ward of a known clinical case) and identified C. auris colonization in another 45 individuals. Patients within similar geographic regions in this study commonly had overlapping stays in the same acute care hospital or long-term care facility, further supporting healthcare exposure as a key method of transmission (
      • Tsay Sharon
      • Welsh Rory
      • Adams Eleanor
      • Chow Nancy
      • Gade Lalitha
      • Berkow Elizabeth
      • et al.
      Notes from the field: ongoing transmission of Candida auris in health care facilities — United States, June 2016–May 2017.
      ).
      Given the risk of nosocomial transmission of this multidrug-resistant pathogen, infection control measures are vital to slowing the spread of C. auris. CDC recommends that all hospitalized patients with C. auris infection or colonization be treated using both Standard Precautions and Contact Precautions (
      • CDC
      Isolation precautions | Guidelines library | Infection control | CDC.
      ) and housed in a private room with daily and terminal cleaning with a disinfectant agent active against Clostridium difficile spores (
      • US EPA OCSPP
      LIST K: EPA’s registered antimicrobial products effective against Clostridium difficile spores.
      ,
      • Cadnum Jennifer L.
      • Shaikh Aaron A.
      • Piedrahita Christina T.
      • Sankar Thriveen
      • Jencson Annette L.
      • Larkin Emily L.
      • et al.
      Effectiveness of disinfectants against Candida auris and other Candida species.
      ). Receiving healthcare facilities should also be notified prior to transfer of an infected or colonized patient. Infection control precautions should be maintained until a patient is no longer infected or colonized with C. auris although there is uncertainty as to how best to monitor for ongoing colonization (
      • CDC
      Candida auris interim recommendations for healthcare facilities and laboratories | Fungal diseases | CDC.
      ). There are no clear data on the efficacy of decolonization measures for patients colonized with C. auris, however this has been attempted with chlorhexidine in healthcare facilities during outbreaks (
      • Schelenz Silke
      • Hagen Ferry
      • Rhodes Johanna L.
      • Abdolrasouli Alireza
      • Chowdhary Anuradha
      • Hall Anne
      • et al.
      First hospital outbreak of the globally emerging Candida auris in a European hospital.
      ,
      • Calvo Belinda
      • Melo Analy S.A.
      • Perozo-Mena Armindo
      • Hernandez Martin
      • Francisco Elaine Cristina
      • Hagen Ferry
      • et al.
      First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia.
      ,
      • European Centre for Disease Prevention and Control
      Candida auris in healthcare settings – Europe.
      ).

      Future directions

      As C. auris cases continue to be found throughout the world, there is urgent need for improved diagnostics, antifungal therapies, and infection control measures. PCR and real-time PCR assays to rapidly identify C. auris have shown excellent accuracy in development and could be performed in laboratories that do not have the ability to perform MALDI-TOF or molecular sequencing techniques (
      • Kordalewska Milena
      • Zhao Yanan
      • Lockhart Shawn R.
      • Chowdhary Anuradha
      • Berrio Indira
      • Perlin David S.
      Rapid and accurate molecular identification of the emerging multidrug resistant pathogen Candida auris.
      ). The development of new antifungal medications with activity against C. auris will be vital to controlling C. auris as therapeutic options are already limited. SCY-078, a novel triterpene glucan synthase inhibitor, is currently in phase III trials for invasive and mucocutaneous candidiasis and has recently shown promising activity in vitro against C. auris (
      • Larkin Emily
      • Hager Christopher
      • Chandra Jyotsna
      • Mukherjee Pranab K.
      • Retuerto Mauricio
      • Salem Iman
      • et al.
      The emerging pathogen Candida auris: growth phenotype, virulence factors, activity of antifungals, and effect of SCY-078, a novel glucan synthesis inhibitor, on growth morphology and biofilm formation.
      ,
      • Berkow Elizabeth L.
      • Angulo David
      • Lockhart Shawn R.
      In vitro activity of a novel glucan synthase inhibitor, SCY-078, against clinical isolates of Candida auris.
      ). Finally, aggressive infection control measures are critical to reducing the spread of C. auris. Antimicrobial stewardship, hand hygiene, and contact precautions will continue to be of paramount importance. More information is needed, however, about effective measures to reduce patient colonization and environmental contamination in healthcare facilities which have served as sites of ongoing transmission of this emerging pathogen.

      Funding sources

      This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

      Conflict of interest

      The authors report no conflicts of interest.

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