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Candida auris, an Emerging Fungal Pathogen

Authors:
Ali Ahmadi at Shahid Beheshti University of Medical Sciences
Ali Ahmadi
Sadegh Khodavaisy at McMaster University
Sadegh Khodavaisy
Shahram Mahmoudi at Iran University of Medical Sciences
Shahram Mahmoudi
Mohammad Kord at Tehran University of Medical Sciences
Mohammad Kord
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Abstract

The emerging pathogen “Candida auris” is attracting considerable international attention due to its rising reports, transmission through health professionals, high rate of treatment failure and resistance to multiple antifungal agents, particularly fluconazole. In spite of the global emergence of C. auris, epidemiological data and true prevalence of infections due to this organism are not clearly determined due to incapability of conventional and biochemical identification methods. Consequently, this species is erroneously identified as C. haemulonii or Rhodotorula glutinis because of their close phenotypical and biochemical resemblance. Therefore, awareness of serious menace posed by C. auris is of great importance for physicians and health laboratory personnel. This awareness could play a beneficial role in prevention of healthcare-associated outbreaks, timely and definite diagnosis, prompt initiation of C. auristargeted therapy, and subsequently improving treatment outcomes. This review aimed to discuss the epidemiology, drug resistance, diagnostic challenges, the mode of transmission, and the strategies for prevention of C. auris-related infections.
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170
Candida auris, an Emerging Fungal Pathogen
Shahram Mahmoudi1,2,
Kazem Ahmadikia2,
Mohammad Kord2,
Ali Ahmadi3,
Sadegh Khodavaisy4
1 PhD Candidate in Medical Mycology, Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
2 PhD Candidate in Medical Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
3 MSc Student in Medical Mycology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
4 Assistant Professor, Department of Medical Parasitology and Mycology, School of Public Health, Tehran University of Medical
Sciences, Tehran, Iran
(Received July 19 , 2018 ; Accepted November 5, 2018)
Abstract
The emerging pathogen “Candida auris” is attracting considerable international attention due to its
rising reports, transmission through health professionals, high rate of treatment failure and resistance to
multiple antifungal agents, particularly fluconazole. In spite of the global emergence of C. auris,
epidemiological data and true prevalence of infections due to this organism are not clearly determined due
to incapability of conventional and biochemical identification methods. Consequently, this species is
erroneously identified as C. haemulonii or Rhodotorula glutinis because of their close phenotypical and
biochemical resemblance. Therefore, awareness of serious menace posed by C. auris is of great
importance for physicians and health laboratory personnel. This awareness could play a beneficial role in
prevention of healthcare-associated outbreaks, timely and definite diagnosis, prompt initiation of C. auris-
targeted therapy, and subsequently improving treatment outcomes. This review aimed to discuss the
epidemiology, drug resistance, diagnostic challenges, the mode of transmission, and the strategies for
prevention of C. auris-related infections.
Keywords: Candida auris, cross infection, emerging pathogen, drug resistance
J Mazandaran Univ Med Sci 2019; 29 (172):170-187 (Persian).
* Corresponding Author: Sadegh Khodavaisy - School of Public Health, Tehran University of Medical Sciences, Tehran,
Iran (E-mail: Sadegh_7392008@yahoo.com)
Downloaded from jmums.mazums.ac.ir at 8:33 +0430 on Wednesday May 8th 2019
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E-mail: Sadegh_7392008@yahoo.com
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ITS1/2D1/D2




Clavispora/Candida


D1/D2









D1/D2
3. Candida haemulonii
4. Candida duobushaemulonii
5. Candida haemulonii var vulnera
Downloaded from jmums.mazums.ac.ir at 8:33 +0430 on Wednesday May 8th 2019
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  

























Galleria mellonella






















Galleria mellonella





























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

















 

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
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
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

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
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
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APACHE II

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
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
CDC






WGS

 


 
1. Whole genome sequencing











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1. Beakpoint
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ERG11
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
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
1. Rezafungin
B
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
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
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CDC
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 VITEK API-20C AUX













































API-20C AUX

Phoenix







VITEK



MicroScan














1. Candida famata
2. Candida Kefyr
3. Candida guilliermondii
4. Candida lusitania
5. Candida glabrata
6. Candida sake






CHROMagar




N












TOF MS-MALDI

PCR






MALDI-TOF MS

FDAMALDIBiotyper
Vitek MS






D1/D2 28SITS 1/2
DNA



PCR
7. Matrix assisted laser desorption ionization-time of flight mass
spectrometry
8. Polymerase chain reaction
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real-time PCR
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DNA
Clavispora cladeITS
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real-time

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T2 Magnetic Resonance assay 
 Multiplex PCR

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
MRSA
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MRSACRE
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
CDC
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


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





1. Methicillin-resistant Staphylococcus aureus
2. Carbapenem-resistant Enterobacteriaceae

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



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... C. auris started attracting considerable global attention due to its growing reports, transmission through health professionals, high rate of treatment failure, and multidrug resistance [19]. C. auris is increasingly becoming a threat to human health because of its intrinsic resistance to one or more classes of antifungal drugs [14,20]. ...
Description of Candida auris Occurrence in a Tertiary Health Institution in Riyadh, Saudi Arabia
Article
Full-text available
  • Dec 2023
Citation: Alshahrani, F.S.; Elgujja, A.A.; Alsubaie, S.; Ezreqat, S.A.; Albarraq, A.M.; Barry, M.; Binkhamis, K.; Alabdan, L. Description of Candida auris Occurrence in a Tertiary Health Institution in Riyadh, Saudi Arabia. Healthcare 2023, 11, 3150. Abstract: Background: Candida auris is an emerging multidrug-resistant fungal pathogen that represents a current serious threat to healthcare settings. Objective: The objective was to determine the prevalence of C. auris in a Riyadh hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts and medical files of all suspected and confirmed cases of C. auris infections reported at King Khalid University Hospital, Riyadh, between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infections in our facility. We analyzed prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed C. auris-positive cases during the study period, 33 (62%) were males. Their ages ranged between 15 and 98, with most positive cases occurring in those aged 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and urine samples yielded the greatest number of positive cases, while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence pattern could serve as a baseline/benchmark to compare with regional and international benchmarks.
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Descriptive View on Candida Auris Occurrence in a Tertiary Health Institution in Riyadh, Saudi Arabia
Preprint
  • Oct 2023
Background Candida auris is an emerging multidrug-resistant fungal pathogen that represents a serious threat to healthcare settings currently. Objective: Its objective was to determine the prevalence of C. auris in the hospital since its initial detection in late 2019. Methods: Using an adapted risk assessment tool, we reviewed the charts. and medical files of all suspected? and confirmed cases of C. auris cases reported at King Khalid University Hospital, Riyadh between November 2019 and December 2022. Anonymized data were retrieved in a pre-established datasheet and analyzed to determine the epidemiological characteristics of C. auris infection in our facility. We established our initial prevalence by age, gender, risk factors, and according to sampling source. Results: Of the 53 confirmed cases positive for C. auris during the study period, 33 (62%) were males. Their ages ranged between 15 and 98; most positive cases occurred in 50 and above. Only one of the confirmed cases was hospital-acquired. All patients had at least one risk factor, and Urine samples yielded the greatest number of positive cases while admission to healthcare facilities constituted the highest risk in our study. Conclusion: Establishing a local prevalence could serve as our baseline/benchmark to compare with regional and international benchmarks.
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Harrison's Principles of Internal Medicine
Chapter
  • Aug 2019
A new, multidrug­resistant species of the fungus Candida, named Candida auris (auris meaning ear in Latin), has emerged recently, causing outbreaks in healthcare facilities. It is of considerable concern because of its resistance to antifungal drugs, association with significant mortality, resistance to decolonization in patients, propensity to be misidentified as other Candida species, lack of identification of environmental sources for colonization, and resistance to removal from rooms and equipment used for patient care. C. auris was first identified in 2009 from the ear drainage of a 70­ year­ old female with ear canal infection in Japan. However, the earliest known strain of C. auris dates back to 1996, isolated in a retrospective analysis of previously misdiagnosed samples from Korea.
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Comparison of 21-Plex PCR and API 20C AUX, MALDI-TOF MS, and rDNA Sequencing for a Wide Range of Clinically Isolated Yeast Species: Improved Identification by Combining 21-Plex PCR and API 20C AUX as an Alternative Strategy for Developing Countries
Article
Full-text available
  • Feb 2019
Occurrence of non-Candida albicans Candida (NCAC) species that are associated with elevated MIC values and therapeutic failures are increasing. As a result, timely and accurate means of identification to the species level is becoming an essential part of diagnostic practices in clinical settings. In this study, 301 clinically isolated yeast strains recovered from various anatomical sites [Blood (n = 145), other sites (n = 156)] were used to assess the accuracy and practicality of API 20C AUX and 21-plex PCR compared to MALDI-TOF MS and large subunit rDNA (LSU rDNA). MALDI-TOF MS correctly identified 98.33% of yeast isolates, 100% of top five Candida species, 95.7% of rare yeast species, while 1.3% of isolates were misidentified. API 20C AUX correctly identified 83.7% of yeast isolates, 97.2% of top five Candida species, 61.8% of rare yeast species, while 16.2% of yeast isolates were misidentified. The 21-plex PCR, accurately identified 87.3% of yeast isolates, 100% of top five Candida species, 72% of rare yeast species, but it misidentified 1.3% of rare yeast species while 9.9% of whole yeast isolates were not identified. The combination of rapidity of 21-plex PCR and comprehensiveness of API 20C AUX, led to correct identification of 92% of included yeast isolates. Due to expensiveness of MALDI-TOF MS and sequencing, this combination strategy could be the most accurate and inexpensive alternative identification strategy for developing countries. Moreover, by the advent and development of cost-effective, reliable, and rapid PCR machines that cost 130 US dollars, 21-plex could be integrated in routine laboratories of developing and resource-limited countries to specifically identify 95% causative agents of yeast-related infections in human. Databases of MALDI-TOF MS, API 20C AUX, and the number of target species identified by 21-plex require further improvement to keep up with the diverse spectrum of yeast species.
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Candida auris otomycosis in Iran and review of recent literature
Article
Full-text available
Candida auris is a multidrug‐resistant yeast emerging in immunocompromised and in otherwise healthy individuals. Due to difficulties in microbiological identification of C. auris because of the lack of available laboratory technology in developing countries, the number of patients affected is most likely underestimated. We report the first case of C. auris otitis which now adds Iran as the fifth country around the Persian Gulf, in addition to Kuwait, Oman, United Arab Emirates and Saudi Arabia. Candida auris is an unknown pathogen in routine laboratories in Iran because most Candida isolates are probably misdiagnosed. Otomycosis seems to be a different clinical presentation of C. auris mainly involving isolates from the East‐Asian clade. We compared the mycological and clinical details of the Iranian patient with other cases of otitis reported since the last review of C. auris otomycosis in 2017.
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Molecular Identification of Clinically Common and Uncommon Yeast Species
Article
Full-text available
  • Sep 2018
Background: The incidence of fungal infections caused by the yeasts and yeast-like species increased dramatically in immunocompromised patients, during the past several decades. However, a few of yeast and yeast-like species may colonize in skin and mucous membranes of healthy individuals. Objectives: The current study aimed at accurately identifying yeast and yeast-like species from clinical samples by molecular methods. Methods: A total of 1200 clinical samples were collected from patients with suspected fungal infection and 110 (9.16 %) yeast and yeast-like strains isolated and identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), PCR amplification of hwp1 gene, and sequencing. Results: In total, Candida albicans (n = 46) was the most frequently isolated species followed by C. parapsilosis complex (n = 17), C. tropicalis (n = 13), C. guilliermondii (n = 12), C. glabrata (n = 4), C. krusei and C. famata each (n = 3), C. kefyr, C. haemulonii and Cutaneotrichosporon jirovecii each (n = 2), and C. stellatoidea, C. intermedia, C. sorbosivorans, C. africana, Pichia kudriavzevii, and Trichosporon asahii each (n = 1). Interestingly, C. haemulonii, a multidrug resistant fungus was isolated from cutaneous and sputum samples for the first time in Iran. Conclusions: Nowadays, with growing population at risk for fungal infections and the emergence of some less virulent or non-pathogenic and uncommon yeasts not readily distinguishable with phenotypic assays, the accurate identification using molecular methods are warranted.
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Isolation of Candida auris from Ear of Otherwise Healthy Patient, Austria, 2018
Article
Full-text available
  • Aug 2018
The emerging pathogen Candida auris is isolated mostly from hospitalized patients and often shows multidrug resistance. We report on the isolation of this yeast in Austria from an outpatient's auditory canal. The isolate showed good susceptibility against antifungals except for echinocandins; the patient was treated successfully with topical administration of nystatin.
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First cases and risk factors of super yeast Candida auris infection or colonization from Shenyang, China
Article
Full-text available
  • Jul 2018
For the first time, we identified 15 cases of Candida auris in Shenyang, China, and then performed a risk factor assessment for these patients compared with 30 control subjects who were hospitalized in the same ward during the same period of time as the infected patients. We found that diarrhea, gastrointestinal decompression, infection, or colonization with other Candida isolates (especially Candida albicans) and tetracycline antibiotics were all risk factors for C. auris infection or colonization. Diarrhea and tetracycline antibiotics were independent risk factors. We suggest clinicians pay special attention to the emergence of multidrug-resistant C. auris infections or colonization.
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Invasive Candida auris infections in Kuwait hospitals: epidemiology, antifungal treatment and outcome
Article
Full-text available
  • Oct 2018
  • INFECTION
Purpose: Candida auris is a recently recognized yeast pathogen, which has attracted worldwide attention due to its multidrug-resistant nature and associated high mortality rates. Its persistence in hospital environment and propensity of nosocomial transmission underscores the need of continuous monitoring to prevent outbreaks. Since the first case of C. auris candidemia in May, 2014, we have identified 17 additional invasive cases, which are described here. Methods: Identity of 17 isolates originating from proven or possible cases of invasive C. auris infection and identified as Candida haemulonii by Vitek 2 yeast identification system was confirmed by PCR-sequencing of rDNA. Information about risk factors, treatment and outcomes were retrospectively retrieved from case files. Antifungal susceptibility testing was performed by Etest. Results: Thirteen cases of candidemia and 4 cases of other invasive infections were detected in 6 hospitals across Kuwait. Major risk factors included adult patients with cancer, diabetes, gastrointestinal/liver diseases and extended (> 25 days) hospital stay. All isolates were resistant to fluconazole. Additionally, 5 and 4 isolates were also resistant to voriconazole and amphotericin B, respectively. Despite antifungal treatment, 9 of 15 patients died. Most patients (n = 12) were hospitalized in 2 hospitals that are in close proximity, whereas 5 other patients were from 3 hospitals that are situated > 10 km apart. Conclusions: Occurrence of successive cases of invasive C. auris infections with resulting mortality in nine patients suggests persistence of this multidrug-resistant yeast in major hospitals in Kuwait. Early detection by continuous surveillance and enforcement of infection control measures are recommended.
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Evaluation of the efficacy of rezafungin, a novel echinocandin, in the treatment of disseminated Candida auris infection using an immunocompromised mouse model
Article
Full-text available
  • Apr 2018
  • J ANTIMICROB CHEMOTH
Background: Multiple cases of Candida auris infection have been reported with high mortality rates owing to its MDR nature. Rezafungin (previously CD101) is a novel echinocandin with enhanced stability and pharmacokinetics that achieves high plasma drug exposure and allows for once weekly dose administration. Objectives: Evaluate the efficacy of rezafungin in the treatment of disseminated C. auris infection using a mouse model of disseminated candidiasis. Methods: Mice were immunosuppressed 3 days prior to infection and 1 day post-infection. On the day of infection, mice were inoculated with 3 × 107C. auris blastospores via the tail vein. Mice were randomized into four groups (n = 20): rezafungin at 20 mg/kg, amphotericin B at 0.3 mg/kg, micafungin at 5 mg/kg and a vehicle control. Treatments were administered 2 h post-infection. Rezafungin was given additionally on days 3 and 6 for a total of three doses, while the remaining groups were treated every day for a total of seven doses. Five mice from each group were sacrificed on days 1, 4, 7 and 10 of the study. Kidneys were removed from each mouse to determine the number of cfu for each respective day. Results: Rezafungin had significantly lower average log10 cfu/g of tissue compared with amphotericin B- and vehicle-treated mice on all days when kidneys were harvested. Additionally, rezafungin-treated mice had significantly lower average log10 cfu/g of tissue compared with micafungin-treated mice on day 10. Conclusions: Our findings show that rezafungin possesses potent antifungal activity against C. auris in a disseminated model of candidiasis.
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Emerging Candida species isolated from renal transplant recipients: Species distribution and susceptibility profiles
Article
  • Sep 2018
Candidiasis is a major challenge among renal transplant recipients (RTRs) worldwide and is associated with high morbidity and mortality rates. Fluconazole is the most commonly used agent for Candida infections. However, frequent relapse and treatment failure are still reported among patients affected with this infection. In the present study, Candida species obtained from RTRs were characterized based on conventional and molecular assays. Furthermore, the antifungal susceptibility profiles of these species were determined. This study was conducted on a total of 126 RTRs within 2012-2016. The patients were categorized according to the referenced diagnostic criteria. The identification of Candida species was accomplished based on conventional examination, assimilation profile test, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The minimum inhibitory concentrations (MICs) of amphotericin B, fluconazole, itraconazole, voriconazole, posaconazole, and caspofungin were determined based on the guidelines of Clinical and Laboratory Standards Institute. The patients with Candida infection were diagnosed with urinary tract candidiasis (n = 17), peritonitis (n = 8), intra-abdominal candidiasis (n = 6), candidemia (n = 4), hepatosplenic candidiasis (n = 3), and Candida pneumonia (n = 3). A total of 41 Candida isolates, including C. albicans (n = 18), C. famata (n = 8), C. kefyr (n = 4), C. tropicalis (n = 4), C. parapsilosis (n = 3), C. glabrata (n = 2), and C. lusitaniae (n = 2), were isolated from 32.5% (41/126) renal transplant recipients. Fluconazole-resistance was observed in seven isolates, entailing C. albicans (n = 6) and C. tropicalis (n = 1). Fluconazole MIC for C. lusitaniae isolates was above the epidemiologic cut-off value (4-16 μg/ml). Furthermore, MIC range values of fluconazole against C. famata and C. kefyr were obtained as 4-32 μg/ml and 4-8 μg/ml, respectively. Posaconazole exhibited potent activity against Candida isolates, followed by caspofungin. The identification of Candida species, together with susceptibility testing, provides important data about the geographic trends of the fluconazole-resistance profiles of Candida species. It is necessary to maintain a consistent method for the implementation of early diagnosis and adoption of treatment regimen.
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Evaluation of a new T2 Magnetic Resonance assay for rapid detection of emergent fungal pathogen Candida auris on clinical skin swab samples
Article
  • Jun 2018
Candida auris is a multidrug‐resistant pathogenic yeast whose recent emergence is of increasing public‐health concern. C. auris can colonize multiple body sites, including patients’ skin, and survive for weeks in the healthcare environment, facilitating patient‐to‐patient transmission and fueling healthcare‐associated outbreaks. Rapid and accurate detection of C. auris colonization is essential for timely implementation of infection control measures and prevent transmission. Currently, axilla/groin composite swabs, used to assess colonization status, are processed using a culture‐based method that is sensitive and specific but requires 14 days. This delay limits the opportunity to respond and highlights the need for a faster alternative. The culture‐independent T2 Magnetic Resonance (T2MR) system is a rapid diagnostic platform shown to detect target pathogens of interest from unprocessed blood samples in <5 hours. In this study, a new C. auris‐specific T2 assay was evaluated for screening of the skin surveillance samples. Inclusivity and limit of detection of the T2 C. auris assay were assessed with spiked samples in a representative skin flora background. The T2 C. auris assay recognized isolates from each of the 4 known clades of C. auris and consistently detected cells at 5 CFU/mL. Finally, 89 clinical axilla/groin swab samples were processed with the T2 C. auris assay. The culture‐based diagnostic assay was used as a gold standard to determine performance statistics including sensitivity (0.89) and specificity (0.98). Overall, the T2 C. auris assay performed well as a rapid diagnostic and could help expedite the detection of C. auris in patient skin swabs. This article is protected by copyright. All rights reserved.
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