The Journal of Infectious Diseases
PERSPECTIVE
The Candida auris Alert: Facts and Perspectives
Frederic Lamoth1,2 and Dimitrios P. Kontoyiannis3
1Infectious
Diseases Service and 2Institute of Microbiology, University Hospital of Lausanne, Switzerland; and 3Department of Infectious Diseases, Infection Control, and
Employee Health, University of Texas M. D. Anderson Cancer Center, Houston
Keywords.  Invasive candidiasis; antifungal resistance; outbreak; infection control
The emergence of multidrug-resistant
microbes is a never-ending threat and
remains a major challenge in modern
infectious diseases treatment and con-
trol. While most attention and public
health efforts have been focused on mul-
tidrug-resistant bacteria, an alert has
recently been issued about the potential
of multiple outbreaks of the uncommon
multidrug-resistant Candida auris. The
recent global spread of this previously
unknown yeast that can be transmitted
nosocomially is intriguing and poses
interesting questions regarding its epide-
miology, pathogenesis, management, and
infection control.
HISTORY AND FACTS
The first descriptions of Candida auris
came from publications from Japan and
South Korea in 2009 [1, 2] and involved
isolates initially misidentified by conven-
tional biochemical tests. Since that time,
invasive infections due to C. auris have
been reported from all continents and
with increasing frequency (Figure 1) [3],
although prevalence in many parts of the
world is difficult to estimate. In India, C.
Received 9 October 2017; editorial decision 10 November
2017; accepted 16 November 2017; published online November
18, 2017.
Correspondence: D. P. Kontoyiannis, MD, ScD, PhD (Hon),
Division of Internal Medicine, Department of Infectious Diseases,
Infection Control and Employee Health, Unit 1460, University
of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd,
Houston, TX 77030 (dkontoyi@mdanderson.org).
The Journal of Infectious Diseases®  2018;217:516–20
© The Author(s) 2017. Published by Oxford University Press for
the Infectious Diseases Society of America. All rights reserved.
For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/infdis/jix597
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auris ranked as the fifth cause of candi-
demia in intensive care units, accounting
for 5.3% of cases [4]. Several outbreaks
have been reported, with the largest
(>50 cases each) occurring in the United
Kingdom (during 2015–2016) and Spain
(during 2016–2017) [5, 6]. Genotypic
analyses identified distinct clades for
each geographical region and the same
clonal origin within each clade [3, 7–10],
suggesting that C. auris was introduced
at different sites and disseminated locally.
In the United States, as of 30 September
2017, 166 clinical cases of C.  auris have
been reported (mostly in New York and
New Jersey), and 184 additional cases
were identified by screening close con-
tacts of patients [11].
The in vitro susceptibility of C.  auris
isolates to antifungal drugs is variable. In
the absence of clinical breakpoints, dif-
ferent thresholds of susceptibility extrap-
olated from closely related Candida
species have been proposed [3, 4, 7].
Most C. auris isolates are resistant to flu-
conazole (minimum inhibitory concen-
tration [MIC] required to inhibit growth
of 90% of organisms, ≥64  µg/mL) [3, 4,
7, 12]. In vitro resistance to voriconazole
is variable (range, 3%–73% of isolates),
while other triazoles (posaconazole,
itraconazole, and isavuconazole) display
better activity [3, 4, 7, 12]. Resistance to
amphotericin B was reported in 13%–
35% of isolates [3, 4, 7]. While most iso-
lates are susceptible to echinocandins,
MICs are higher than those for Candida
albicans [3, 4, 7, 12]. Echinocandins
are the most effective drugs in animal
models [13]. Of concern, about 40% of
C. auris isolates are resistant to ≥2 anti-
fungal drug classes, and 4%–10% are
resistant to most antifungal agents [3,
12]. Deciphering the mechanisms of
resistance in C.  auris is work in prog-
ress. Several erg11 mutations known to
be associated with azole resistance have
been identified and were related to dis-
tinct geographical clades [3]. Functional
genome annotation showed that the
C. auris genome encodes multiple trans-
porters of the ABC family and the major
facilitator superfamily and is phylogenet-
ically close to that of Candida lusitaniae,
another fungus capable of rapid induc-
tion of resistance [14]. Sequencing of
hotspots in the fks genes of C. auris iso-
lates with elevated echinocandin MICs
did not detect any mutation [10, 12].
WHY HAS C. AURIS EMERGED
RECENTLY?
Because C.  auris was unknown before
2009, the question arises whether this
species is a newcomer in the world of
pathogenic fungi or simply has been
not previously recognized. Isolates of
C.  auris have been commonly mis-
identified as Candida haemulonii,
Candida famata, Rhodotorula glutinis,
Saccharomyces cerevisiae, or unspecified
Candida species. using conventional
biochemical diagnostic procedures.
The advent of molecular techniques
and recent improvements in mass
spectrometry (ie, matrix-assisted laser
desorption ionization–time of flight
[MALDI-TOF] mass spectrometry)
 Origin of clades
East Asia (Japan, South Korea)
South Asia (India, Pakistan, Kuwait)
Sample size
< 10 cases 10 –50 cases
Figure 1.  Geographical distribution of Candida auris cases and outbreaks reported in the world. Only cases reported in the medical literature are shown. The size of the
circles is representative of the number of cases. The colors represent the different clades that have been described. Cases from the United States and Great Britain are dis-
tributed in different clades.
databases allow better recognition of
this pathogen. Although C.  auris was
identified in a few clinical samples
20 years ago [2, 15], several lines of evi-
dence indicate that C. auris has emerged
as a novel pathogenic Candida species
only during the last decade. Analysis
of the international SENTRY collec-
tion (15 271 Candida isolates, collected
between 2004 and 2015) identified only
4 C.  auris isolates, all collected since
2009 [3]. None of the US cases were
identified prior to 2013 [16].
The fact that C.  auris infections are
mainly observed among patients with pre-
vious antifungal exposure suggests that
selective pressure could have played a role
in the emergence of this novel pathogen
[3, 4]. However, the shift in Candida epi-
demiology, with an increasing proportion
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Israel
South Africa
≥50 cases
of non-albicans and azole-resistant
Candida species, has long preceded the
emergence of C. auris [17].
The emergence of C. auris as a human
pathogen could have been linked to
the acquisition of new virulence traits.
However, the identification of distinct
geographical clades indicates that this
genetic event should have occurred
simultaneously and independently in
different parts of the world (Figure  1)
[3, 9]. Our understanding of patho-
genesis of C. auris infection is in early
stages, although promising genome
modification systems are being devel-
oped [18]. C. auris possesses the arma-
mentarium required to infect humans
and shares virulence traits encountered
in other pathogenic Candida species,
including host cell adherence, biofilm
PERSPECTIVE • JID 2018:217 (15 February) • 517
South America
Unspecified
formation, and invasive properties
[13, 19]. The virulence of C.  auris
appears to be comparable to that of
C. albicans in experimental mouse and
Galleria models of infection [19, 20]
and higher than that of C.  albicans in
Toll-deficient flies (D. P. Kontoyiannis,
unpublished data). Other intriguing
questions regarding the pathogenesis
of C. auris remain open: What can we
learn by comparative genomic analysis
of C.  auris versus C.  albicans? Is there
strain-strain variability to virulence,
host responses, and propensity of inva-
sive disease/dissemination? Is C.  auris
a permissive or conditional part of
human mycobiome? Is there a natural
reservoir and an event that triggered a
change of its ecological niche to affect
humans?
 WHY DOES C. AURIS REPRESENT
A PUBLIC HEALTH CHALLENGE?
C. auris exhibits all the characteristics of a
pathogen of public health concern, compa-
rable to multidrug-resistant bacteria such
as methicillin-resistant Staphylococcus
aureus, or carbapenemase-producing
Enterobacteriaceae. These include (1) the
potential to spread by horizontal trans-
mission and cause outbreaks; (2) the abil-
ity to cause severe, even fatal disease; and
(3) the multidrug-resistant profile and
paucity of antimicrobial armamentarium.
Contrary to most Candida infections,
which arise from the commensal flora,
C.  auris has high potential for interhu-
man transmission. Isolates recovered
from the same healthcare unit shared the
same clonal origin [3, 5, 7, 8]. Moreover,
isolates from the same cluster were recov-
ered in distant hospitals within a same re-
gion, supporting modes of transmission
within the community. The introduction
of C. auris in the United Kingdom and the
United States is believed to have resulted
from travelers having received healthcare
in countries where the fungus is endemic
[5, 16]. However, other unknown modes
of propagation are possible.
C. auris has the ability to form biofilms
on polymeric surfaces and has been recov-
ered in environmental samples from hos-
pital rooms during outbreaks [5, 6, 21]. In
vitro studies showed that, despite form-
ing less biofilm than C. albicans, C. auris
has a greater capacity to persist and
survive on dry or moist surfaces [22–24].
Similar persistence properties were
described for Candida parapsilosis [24],
but evidence of nosocomial transmis-
sion of C.  parapsilosis or other Candida
species has been only anecdotally re-
ported [25, 26]. Actually, C. auris may ex-
hibit 2 phenotypes: an aggregative form
with enhanced resistance to physical or
chemical disruption, favoring persist-
ence in the environment or in the host,
and a nonaggregative form with higher
capacity to form biofilm [19, 21]. The as-
sociation between C. auris infections and
invasive procedures further supports the
risk of nosocomial transmission via con-
taminated medical devices [4].
Overall mortality of C. auris infections
is high (40%–60%), which is due in part
to the severe underlying conditions of the
patients and the multidrug-resistant na-
ture of this pathogen [3–5], as persistent
candidemia is common [7, 8]. The lim-
ited therapeutic choices in conjunction
with the nosocomial persistence of the
fungus raise the nightmarish scenario of
large-scale nosocomial outbreaks.
FUTURE DIRECTIONS
It is difficult to predict the impact of
C. auris epidemics or even pandemics in
the future, but this certainly depends on
the actions that will be undertaken at this
stage to manage this urgent situation.
Strategies of prevention and infec-
tion control should be of paramount
importance for C.  auris, as it should be
for all multidrug-resistant nosocomial
microbes (Table  1). Sporicidal surface
disinfectants, such as peroxide hydro-
gen vapor and sodium hypochlorite–
based agents used against Clostridium
difficile, are active, while quaternary
ammonium disinfectants are not [5, 27].
Chlorhexidine is active against C.  auris
and has been used for skin decolonization
of cases detected by contact screening, but
persistent colonization is common [5, 21].
Identification of potential reservoirs and
early recognition of cases, including sys-
tematic screening of patients coming
from a region with high prevalence of
C.  auris infection, are important to pre-
vent outbreaks. Screening of multiple
sites is recommended, including groin,
axilla, and nares [28]. Such screening
might be also important for the safety of
organ transplantation, as donor-derived
transmission of C. auris has been already
described [29].
The optimal treatment of C. auris infec-
tion remains to be defined. Echinocandins
are currently recommended as first-line
treatment because most isolates are sus-
ceptible. Addition of amphotericin B
is recommended by experts in case of
persistent fungemia or lack of clinical
response [28]. The role of isavuconazole,
the most active triazole in vitro, should
be further defined. Drug combinations
should also be investigated, because syn-
ergistic interactions between voriconazole

Table 1.  Hallmarks Making Candida auris a Major Public Health Issue and Proposed Interventions

Hallmark Threat Control/Prevention

Increased prevalence, unknown
origin
Simultaneous emergence on
different continents
Misidentification by diagnostic
laboratories
Biofilm formation,
persistence/survival in the
environment
Antifungal resistance (intrinsic or Emergence of multidrug- or pan-drug–resistant
rapidly inducible)
Continuous increase in the future leads to
emergence of C. auris as a frequent cause of
nosocomial infections
Worldwide dissemination leads to pandemics of
C. auris infection
Lack or delayed recognition of clinical cases leads
to occult outbreaks
Interhuman transmission leads to nosocomial
outbreaks
Limit antifungal drug overuse, develop of novel antifungal therapies
strains leads to outbreaks with high mortality rate
Investigate potential sources/reservoirs,
conduct epidemiological surveys in large prospective cohorts
Investigate environmental sources/reservoirs
Improve development and access to new diagnostic tools (MALDI-TOF
mass spectrometry, molecular techniques), improve training of laboratory
personnel
Screen patients, create hospital hygiene plans (isolation/disinfection),
improve decontamination of surfaces (sporicidal agents)

Abbreviation: MALDI-TOF, matrix-assisted laser desorption ionization–time of flight.

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 and micafungin were observed [30].
Antifungal treatment is not recommended
for patients who are only colonized. In
view of the frequent resistance of C. auris
to modern antifungals, there is a need
to expand our preclinical and ultimately
clinical testing to investigational antifun-
gals [31]. For example, a potent inhibitory
effect and antibiofilm activity has been
shown with the novel 1,3-β-d-glucan syn-
thase inhibitor SCY-078 [22].
The mycology community needs also to
invest more in studying the epidemiology
and diagnosis of C. auris infections. Large
epidemiological surveys and international
networks, such as the SENTRY antifungal
surveillance program, have been devel-
oped, but data are lacking for many parts
of the world. Improving access to molecu-
lar tools and MALDI-TOF mass spectrom-
etry in developing countries is important.
Finally, education of the public and of
healthcare providers should be comple-
mentary to infection control, antifungal
stewardship, and containment efforts.
The unprecedented emergence of
C. auris is a timely reminder that, as with
many bacteria, fungal pathogens deserve
equal attention from policy makers, sci-
entists, drug developers, and treating
physicians.
Notes
Potential conflicts of interest. D.  P.
K.  has received research support from
Merck, Pfizer, Astellas, and T2 Biosystems
and has received honoraria from Merck,
Astellas, Gilead, Amplyx, Scynexis, and
Jazz Pharmaceuticals. F. L. reports no po-
tential conflicts. All authors have submitted
the ICMJE Form for Disclosure of Potential
Conflicts of Interest. Conflicts that the edi-
tors consider relevant to the content of the
manuscript have been disclosed.
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