Global epidemiology of emerging Candida auris

doi:10.1016/j.mib.2019.05.008

Current Opinion in Microbiology

Volume 52, December 2019, Pages 84-89

https://doi.org/10.1016/j.mib.2019.05.008 Get rights and content

Highlights

•
Candida auris is a newly identified and globally emerging fungal infection.
•
C. auris shows extensive innate and acquired resistance to antifungal drugs.
•
The fungus is intrinsically resistant to widely used hospital disinfectants leading to high rates of nosocomial transmission.
•
Research into virulence and treatment of C. auris in susceptible patients is urgently needed.

The discovery in 2009 of a new species of yeast, Candida auris, heralded the arrival of a novel emerging human infectious disease. This review highlights the unique characteristics of C. auris that have lled to it being of public health concern worldwide, namely public health concern, namely its global emergence, its ability to cause nosocomial outbreaks in healthcare settings, its innate and emerging resistance to multiple antifungal drugs and its resilience in the face of hygiene and infection control measures. Genomic epidemiology has identified four emergences of C. auris marked by four clades of the pathogen. These clades of C. auris are genetically dissimilar and are associated with differential resistance to antifungal drugs, suggesting that they will continue to phenotypically diverge into the future. The global emergence of C. auris testifies to the unmapped nature of Kingdom Fungi, and represents a new nosocomial threat that will require enhanced infection control across diverse healthcare and community settings.

Introduction

Since its discovery in 2009 [1^•], Candida auris has been identified in more than 30 countries on six continents [2^•]. A retrospective SENTRY review identified a 2008 isolation from Pakistan; however, C. auris is generally considered rare before 2009 suggesting that it represents a newly emerging human infection. In contrast to other Candida species, C. auris spreads easily in health-care setting causing nosocomial outbreaks [3,4]. This fungus’ ability to persist, both on the human host and also on inanimate surfaces, has been well documented [5,6] and is likely a key trait explaining its emergence. Exhibiting intrinsic resistance to fluconazole [7^•] and variable susceptibility to other azole antifungal drugs, 5-flucytosine [8^•], amphotericin B [9], and echinocandins [8^•,10,11], C. auris has been widely acknowledged as multi-drug resistant (MDR) [12,13]. This, along with its ability to persist and easily transmit, alongside its highly proliferative clonal life-history, has led to C. auris’ pandemic potential by causing an expanding range of nosocomial infections worldwide [1^•,3,7^•,14, 15, 16, 17, 18].

Section snippets

Emergence of C. auris

C. auris was first discovered and described in 2009 following isolation from discharge from the ear canal of a patient in Japan [1^•] and was taxonomically placed as a close relative to the Candida haemulonii complex. Since its discovery, C. auris has caused a ‘stealthy pandemic’, emerging across the globe (Figure 1) and is now recorded in all continents except Antarctica (Figure 2). However, C. auris is thought to have been misidentified as C. haemulonii on a number of occasions [4,13,19],

Genomic epidemiology

Investigation into the C. auris genome has shown it to possess over 5000 protein coding genes [7^•,8^•,21], and expresses several virulence factors such as biofilm formation and adherence [22,23], although to a lesser extent than C. albicans [22,24]. Muñoz et al. performed RNA-seq and discovered expansions of entire gene families were linked to drug resistance and virulence [21], which have also been described in C. albicans [25]. Whilst the roles of specific genes were not characterised as part

Antifungal resistance and transmission in C. auris

Currently, candidaemia infections caused by C. albicans are widely managed via the use of echinocandin therapy, and in some cases in combination with amphotericin B [17,32]. Intravenous amphotericin B not in combination with another drug has resulted in treatment failure [15]; however, the mechanistic nature of this resistance is not yet understood. Whilst there are currently no established breakpoints for antifungal susceptibility in C. auris, it is generally accepted that most isolates are

Future directions

Currently, nothing is known about the origins and initial emergence of C. auris; its propensity to survive on inanimate objects within the hospital alongside resistance to disinfection protocols suggests the existence of an unknown non-human environmental reservoir. However, similar to other Candida species, the true nature of C. auris’ ancestral reservoirs currently remains elusive [42, 43, 44]. The detection of clonal C. auris isolates on multiple continents simultaneously with distinct

Acknowledgements

JR and MCF were supported by UK NERC (NE/P001165/1) and the UK MRC (MR/R015600/1). MCF is a Canadian CIFAR Fellow in the ‘Fungal Kingdom’ program.

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Cited by (164)

Intrahospital transmission and infection control of Candida auris originating from a severely infected COVID-19 patient transferred abroad
2024, Journal of Hospital Infection
Intrahospital spread of Candida auris, which survives tenaciously in many environments, can cause sustained colonization and infection. A large outbreak of C. auris was experienced in the intensive care units (ICUs) at the study hospital during the coronavirus disease 2019 (COVID-19) pandemic.
The index patient with severe COVID-19, who was transferred from Vietnam in January 2022, developed C. auris candidaemia 10 days after hospitalization. From mid-June 2022 to January 2023, strengthened infection prevention and control (IPC) measures were implemented in three ICUs: (1) contact precautions and isolation (CPI) for C. auris-positive cases; (2) surveillance cultures including point-prevalence (N=718) for patients or close contacts or ICU-resident healthcare workers (HCWs); (3) intensive environmental disinfection with 10-fold diluted bleach; and (4) 2% chlorhexidine bathing for all ICU patients. Environmental cultures (ECx) on surfaces and shared objects (N=276) were conducted until early September 2022, when all ECx were negative.
Among 53 C. auris-positive patients between February 2022 and January 2023, invasive infections resulted in seven cases of candidaemia and one case of pneumonia. C. auris was isolated from reusable tympanic thermometers (TTMs) contaminated with earwax. The isolation rate of C. auris in ECx decreased from 6.8% in June 2022 to 2.0% in August 2022, and was no longer detected in TTMs. Colonization in HCWs was remarkably rare (0.5%). The number of C. auris-positive patients peaked in July (N=10) then decreased gradually. By January 2023, no C. auris were isolated in the ICU.
Aggressive IPC measures with CPI, ECx and surveillance, decontamination of TTMs, and bathing were effective in successfully controlling this C. auris outbreak.
Development of an antagonistic active beverage based on a starter including Acetobacter and assessment of its volatile profile
2024, International Dairy Journal
Health deterioration and the growth of opportunistic infections require the search for safe and effective means of combating pathogens. Acetic acid bacteria (AAB) are constant companions of lactic acid bacteria (LAB) and yeasts in naturally fermented products and have many health benefits. However, the use of AAB in the dairy industry is limited. Our research revealed AAB species not previously noted in koumiss. After creating associations of newly isolated LAB and AAB, the fermented milk beverage was created. The inclusion of Acetobacter pasteurianus/oryzoeni 2–6 in the starter of Lactobacillus delbrueckii 3KUM11 and Streptococcus thermophilus 3KUM12 provided strong anti-Candida albicans antagonism and significantly increased inhibition of intestinal Gram-negative bacteria with the simultaneous shift in volatile profile towards increasing of acetic acid but not affecting the sensory properties. In yeast-added beverage, AAB also decreased levels of alcohol and esters.
Strain and temperature dependent aggregation of Candida auris is attenuated by inhibition of surface amyloid proteins
2023, The Cell Surface
Candida auris is a multi-drug resistant human fungal pathogen that has become a global threat to human health due to its drug resistant phenotype, persistence in the hospital environment and propensity for patient to patient spread. Isolates display variable aggregation that may affect the relative virulence of strains. Therefore, dissection of this phenotype has gained substantial interest in recent years. We studied eight clinical isolates from four different clades (I-IV); four of which had a strongly aggregating phenotype and four of which did not. Genome analysis identified polymorphisms associated with loss of cell surface proteins were enriched in weakly-aggregating strains. Additionally, we identified down-regulation of chitin synthase genes involved in the synthesis of the chitinous septum. Characterisation of the cells revealed no ultrastructural defects in cytokinesis or cell separation in aggregating isolates. Strongly and weakly aggregating strains did not differ in net surface charge or in cell surface hydrophobicity. The capacity for aggregation and for adhesion to polystyrene microspheres were also not correlated. However, aggregation and extracellular matrix formation were all increased at higher growth temperatures, and treatment with the amyloid protein inhibitor Thioflavin-T markedly attenuated aggregation. Genome analysis further indicated strain specific differences in the genome content of GPI-anchored proteins including those encoding genes with the potential to form amyloid proteins. Collectively our data suggests that aggregation is a complex strain and temperature dependent phenomenon that may be linked in part to the ability to form extracellular matrix and cell surface amyloids.
A random spatio-temporal model for the dynamics of Candida Auris in Intensive Care Units with regular cleaning
2023, Physica A: Statistical Mechanics and its Applications
Candida Auris is a pathogen that can express multiple virulence factors and is considered a significant menace to the Intensive Care Unit environment. In this work, we propose to model its growth with a computationally randomized Fisher Kolmogorov–Petrovsky–Piskunov partial differential equation. We calibrate the model using in vitro growth data and provide statistical features. We also evaluate the efficacy of a regular and uniform cleaning strategy with vaporized hydrogen peroxide to control Candida Auris’ population in ICUs.
In-vivo efficiency of the novel azole compounds (ATTAF-1 and ATTAF-2) against systemic candidiasis in a murine model
2023, Journal of Medical Mycology
Antifungal resistance is the main health concern in the control of invasive fungal infections. This research was designed to further assess the antifungal activity of aryl-1,2,4-triazole-3-ylthio analogs of fluconazole (ATTAFs) against Candida albicans systemic candidiasis in the murine model.
The murine model of systemic candidiasis was designed via the inoculation of 1 × 10⁶ CFU of Candida albicans. The treatment dosages of 3.5 and 35 mg/kg per day were selected for ATTAFs and fluconazole, respectively. The median survival time (MST) was assayed for 30 days post-infection. The quantitative and qualitative (via histopathology staining) fungal burden was also assessed. Furthermore, immunohistochemistry and biochemistry assays were performed to monitor anti-inflammatory activity using the Cyclooxygenase-2 (Cox-2) marker and changes in serum protein levels.
ATTAFs considerably improved the survival of the murine model (P < 0.003). Compared with fluconazole, the antifungal activity of ATTAFs and their MST showed no difference (P > 0.05). However, these compounds decreased the fungal burden in the kidneys, spleen, and liver.
Our research indicates that ATTAF-1 and ATTAF-2 are effective therapeutic agents due to their fungal clearing and increasing the MST in the murine model of systemic candidiasis. Although we concluded that these components are novel and promising candidates for the management of invasive candidiasis, further studies are warranted to correlate these findings with clinical outcomes.
European candidaemia is characterised by notable differential epidemiology and susceptibility pattern: Results from the ECMM Candida III study
2023, Journal of Infection
The objectives of this study were to assess Candida spp. distribution and antifungal resistance of candidaemia across Europe. Isolates were collected as part of the third ECMM Candida European multicentre observational study, conducted from 01 to 07-07-2018 to 31-03-2022. Each centre (maximum number/country determined by population size) included ∼10 consecutive cases. Isolates were referred to central laboratories and identified by morphology and MALDI-TOF, supplemented by ITS-sequencing when needed. EUCAST MICs were determined for five antifungals. fks sequencing was performed for echinocandin resistant isolates. The 399 isolates from 41 centres in 17 countries included C. albicans (47.1%), C. glabrata (22.3%), C. parapsilosis (15.0%), C. tropicalis (6.3%), C. dubliniensis and C. krusei (2.3% each) and other species (4.8%). Austria had the highest C. albicans proportion (77%), Czech Republic, France and UK the highest C. glabrata proportions (25–33%) while Italy and Turkey had the highest C. parapsilosis proportions (24–26%). All isolates were amphotericin B susceptible. Fluconazole resistance was found in 4% C. tropicalis, 12% C. glabrata (from six countries across Europe), 17% C. parapsilosis (from Greece, Italy, and Turkey) and 20% other Candida spp. Four isolates were anidulafungin and micafungin resistant/non-wild-type and five resistant to micafungin only. Three/3 and 2/5 of these were sequenced and harboured fks-alterations including a novel L657W in C. parapsilosis. The epidemiology varied among centres and countries. Acquired echinocandin resistance was rare but included differential susceptibility to anidulafungin and micafungin, and resistant C. parapsilosis. Fluconazole and voriconazole cross-resistance was common in C. glabrata and C. parapsilosis but with different geographical prevalence.

View all citing articles on Scopus

View full text

Global epidemiology of emerging Candida auris

Highlights

Introduction

Section snippets

Emergence of C. auris

Genomic epidemiology

Antifungal resistance and transmission in C. auris

Future directions

Acknowledgements

Antimicrob Resist Infect Control

Clin Inf Dis

Mol Microbiol

Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital

Microbiol Immunol

Multiple introductions and subsequent transmission of multidrug-resistant Candida auris in the USA: a molecular epidemiological survey

Lancet Infect Dis

Candida auris: a rapidly emerging cause of hospital-acquired multidrug-resistant fungal infections globally

PLoS Pathog

In vitro efficacy of disinfectants utilised for skin decolonisation and environmental decontamination during a hospital outbreak with Candida auris

Mycoses

Survival, persistence, and isolation of the emerging multidrug-resistant pathogenic yeast Candida auris on a plastic health care surface

J Clin Microbiol

Simultaneous emergence of multidrug resistant Candida auris on three continents confirmed by whole genome sequencing and epidemiological analyses

Clin Infect Dis

Genomic epidemiology of the UK outbreak of the emerging human fungal pathogen Candida auris

Emerg Microbes Infect

Molecular epidemiology of Candida auris in Colombia reveals a highly related, countrywide colonization with regional patterns in amphotericin B resistance

Clin Infect Dis

Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris

Diagn Microbiol Infect Dis

A multicentre study of antifungal susceptibility patterns among 350 Candida auris isolates (2009–17) in India: role of the ERG11 and FKS1 genes in azole and echinocandin resistance

J Antimicrob Chemother

Multidrug-resistant endemic clonal strain of Candida auris in India

Eur J Clin Microbiol Infect Dis

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

J Clin Microbiol

New clonal strain of Candida auris, Delhi, India

Emerg Infect Dis

First three reported cases of nosocomial fungemia caused by Candida auris

J Clin Microbiol

Investigation of the first seven reported cases of Candida auris, a globally emerging invasive, multidrug-resistant fungus-United States, May 2013-August 2016

Am J Transplant

First report of Candida auris in America: clinical and microbiological aspects of 18 episodes of candidemia

J Infect

Invasive infections with multidrug-resistant yeast Candida auris, Colombia

Emerg Infect Dis

Candida auris-associated candidemia, South Africa

Emerg Infect Dis

Candida haemulonii and closely related species at 5 university hospitals in Korea: identification, antifungal susceptibility, and clinical features

Clin Infect Dis

Genomic insights into multidrug-resistance, mating and virulence in Candida auris and related emerging species

Nat Commun