Vanessa Hurtado

March 21, 2022

Candida auris: An Emerging Fungal Pathogen

Around the globe, several countries have reported an increasing incidence of infection
with the multi-drug resistant, pathogenic yeast Candida auris. The yeast was first
isolated in 2009 from the ear discharge of a female patient in Tokyo, Japan, hence the
species name “auris”, which means “ear” in Latin (Du et al, 2020). Since then, the
Centers for Disease Control and Prevention (CDC) has identified C. auris as an
“emerging pathogen” in the United States due to its propensity for outbreaks in long-
term health care facilities, hospitals, and skilled nursing facilities (CDC, 2019). The
pathogenic yeast poses a high risk to immunocompromised patients and can result in
invasive candidiasis or candidemia. Once in the bloodstream, the yeast disseminates
throughout the body and infection is often fatal. As with other invasive Candida
infections, the presence of C. auris in the blood has a high mortality rate, ranging
between 30-60%, worldwide (Du et al, 2020). Given its resistance to multiple antifungal
agents, high mortality rates, and rapid emergence, finding an effective treatment for C.
auris infection has become extremely important. As of 2020, antifungal echinocandin
drugs have proven to be effective as the first line of treatment, however, concerns
regarding the increasing rates of resistance to these drugs has triggered the need for
more research and development of alternative therapies. One alternative drug, known
as ibrexafungerp, has shown promising results for treating C. auris infections, and is
worthy of exploration.

Before diving into treatment options for C. auris infections, it is important to understand
the mechanisms behind its high transmissibility as it relates to the yeast’s virulence
factors. As with other Candida species, certain virulence factors such as biofilm
formation, germination, adherence, and enzyme production contribute to the
pathogenesis of C. auris (Spivak & Hanson, 2018). Additionally, two unique features of
C. auris are its ability to grow in warmer temperatures and in high salt concentrations,
compared to other species of Candida (Du et al, 2020). Most fungi cannot tolerate such
conditions and are unable to colonize the human body and cause infections, however,
researchers have suggested that this tolerance could be an evolutionary adaptation of
C. auris to survive during environmental stress – specifically in conditions created by
global warming. Furthermore, studies have shown that C. auris can survive on skin and
nonbiological surfaces for several weeks and has become increasingly resistant to
commonly used disinfectants (Du et al, 2020). Researchers consider these factors to be
major contributors to the rise and persistence of C. auris infections in hospitals and
other clinical settings.

Once C. auris has entered the bloodstream, quick and effective treatment is crucial for
patient survival. As recommended by the CDC, patients should seek consultation with
infectious disease specialists or physicians specializing in mycoses to ensure the best
course of treatment (CDC, 2021). The first line of treatment for C. auris candidemia has
been with antifungal agents of the echinocandin class, including anidulafungin,
caspofungin, and micafungin. However, cases of resistance to these drugs have been
steadily increasing over the last decade, so other alternatives are being explored. If the
patient experiences failed treatment with echinocandin drugs, the CDC recommends
 Vanessa Hurtado
March 21, 2022

switching to a liposomal amphotericin B treatment, or combination antifungal treatment

(CDC, 2021). Still, most studies have only been conducted in vitro and have yet to be
evaluated in clinical settings, making it difficult to treat patients infected with
echinocandin-resistant strains. This critical need for alternative treatments has led to the
discovery of a novel drug called ibrexafungerp. This compound is a β-D-glucan
synthase inhibitor, similar to echinocandins, however, it is the first oral and intravenous
drug being developed for the treatment and prevention of life-threatening infections with
certain fungi, including Candida, Aspergillus, and Pneumocystis jirovecii (Ghannoum et
al, 2020).
Ibrexafungerp works by targeting β-D-glucan polymers and weakening the cell
wall, but it differs from echinocandins in its specificity for a separate binding site on the
target enzyme, β-D-glucan synthase. This site specificity confers a lower rate of
resistance to ibrexafungerp compared to the echinocandin drugs (Ghannoum et al,
2020). According to Ghannoum et al (2020), in vitro studies have shown that
ibrexafungerp is particularly effective against point mutations in C. auris strains, which
are associated with their resistance to echinocandins. Furthermore, ibrexafungerp has
shown promising activity against C. auris biofilms by slowing metabolic activity and
reducing their thickness. As for in vivo studies, Ghannoum et al (2020), describes two
patients treated with ibrexafungerp who demonstrated a complete response to oral
treatment with very mild to no side effects. These early studies are sure to inspire more
clinical trials with ibrexafungerp and perhaps lead to the discovery of more treatment
options for infections with C. auris.
 Vanessa Hurtado
March 21, 2022

References

Du, H., Bing, J., Hu, T., Ennis, C. L., Nobile, C. J., & Huang, G. (2020). Candida auris:
Epidemiology, biology, antifungal resistance, and virulence. PLoS pathogens, 16(10),
e1008921. https://doi.org/10.1371/journal.ppat.1008921

Centers for Disease Control and Prevention. (2019, November 13). General information
about candida auris. Centers for Disease Control and Prevention. Retrieved March 21,
2022, from https://www.cdc.gov/fungal/candida-auris/candida-auris-qanda.html

Spivak, E. S., & Hanson, K. E. (2018). Candida auris: an Emerging Fungal

Pathogen. Journal of clinical microbiology, 56(2), e01588-17.
https://doi.org/10.1128/JCM.01588-17

Centers for Disease Control and Prevention. (2021, July 22). Treatment and
management of infections and colonization. Centers for Disease Control and
Prevention. Retrieved March 21, 2022, from https://www.cdc.gov/fungal/candida-auris/c-
auris-treatment.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Ffungal
%2Fdiseases%2Fcandidiasis%2Fc-auris-treatment.html

Ghannoum, M., Arendrup, M. C., Chaturvedi, V. P., Lockhart, S. R., McCormick, T. S.,
Chaturvedi, S., Berkow, E. L., Juneja, D., Tarai, B., Azie, N., Angulo, D., & Walsh, T. J.
(2020). Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the
Treatment of Candida auris Infections. Antibiotics (Basel, Switzerland), 9(9), 539.
https://doi.org/10.3390/antibiotics9090539