Emerging yeast infections in Asia

Professor Arunaloke Chakrabarti
Head, Postgraduate Institute of Medical Education and Research, India
President-elect, International Society for Human and Animal Mycology (ISHAM)
Co-chair, Asia Fungal Working Group

With the advancement of modern medicine and a growing population of immunosuppressed patients, opportunistic yeast infections have become an important cause of morbidity and mortality in critically ill patients. Interestingly, certain unusual opportunistic yeast species have emerged for the first time and other known rare yeasts have appeared more often in the last decade. In the last two decades, the incidence of non-albicans Candida species infection has increased relative to C. albicans worldwide, but the shift is more marked in some Asian countries, where non-albicans Candida species account for ~90% of candidemia cases.

The emergence of multidrug-resistant C. auris is the latest threat in Asia, and the infection has spread to South Africa, United Kingdom and United States in the last 2 years. In fact, the Centers for Disease Control and Prevention (CDC) issued a clinical alert titled ‘Global Emergence of Invasive Infections Caused by the Multidrug-Resistant Yeast Candida auris’ on June 24, 2016. In addition, several unusual yeast species (Pichia anomala, P. fabianii and Kodamaea ohmeri) were found to be responsible for large outbreaks in India. C. africana, a cryptic species of C. albicans, has recently been reported to cause vulvovaginitis and balanoposthitis in China. Trichosporonosis due to multidrug-resistant Trichosporon asahii is frequently encountered in China, India, Japan, Taiwan and Thailand. Non-neoformans Cryptococcus species like C. gattii and C. laurentii have been reported in both immunocompetent and immunosuppressed patients in a few Asian countries. Other uncommon yeasts reported from Asia include Geotrichum, Malassezia, Rhodotorula and Saccharomyces species. Malassezia japonica and M. arunalokei are two new species isolated from clinical specimens in the region. Saccharomyces fungemia related to use of probiotics has raised concern in critically ill patients of India.

The exact reason for the emergence of these yeast infections is largely unknown. However, improved diagnostics, especially molecular techniques (eg, matrix-assisted laser desorption/ionization [MALDI], sequencing), have played important roles in the identification of the majority of emerging yeasts. The commercially available biochemical-based tests (eg, VITEK-2, API strips) cannot correctly identify all yeasts, so molecular techniques are required. The accurate identification of yeasts is of paramount importance when choosing the proper antifungal agent, as yeasts differ in virulence and drug resistance. The usual antifungal susceptibility of emerging yeasts in Asia is summarized in the Table.

Table. Antifungal activity in emerging yeasts

Azoles				Polyenes	Echinocandins
	Fluconazole	Voriconazole	Posaconazole	Amphotericin	All three
Candida tropicalis	~10% resistant	5-10% resistant	Susceptible	Susceptible	Susceptible
C. glabrata	Dose-dependent	Susceptible/ dose-dependent	Variable	Susceptible	Susceptible
C. krusei	Resistant	Dose-dependent	Dose-dependent	Susceptible to intermediate	Susceptible
C. parapsilosis	Susceptible	Susceptible	Susceptible	Susceptible	Higher MIC
C. auris	Resistant	Resistant in majority	Variable	~14% resistant	~10% resistant to caspofungin
C. rugosa	Low activity	Low activity	Low activity	Susceptible	Susceptible
C. guilliermondii	Low activity	Susceptible	Susceptible	Susceptible	Susceptible
Pichia anomala	Variable	Susceptible	Susceptible	Susceptible	Susceptible
Kodamaea ohmeri	Susceptible	Susceptible	Susceptible	Variable	Susceptible
Trichosporon asahii	Variable	Susceptible	Susceptible	Resistant	Resistant
Cryptococcus gattii	Low activity	Susceptible	Susceptible	Susceptible	Resistant
Rhodotorula species	Low activity	Variable	Not known	Susceptible	Resistant
Saccharomyces species	Variable	Susceptible	Susceptible	Susceptible	Susceptible
Malassezia species	Variable	Susceptible	Not known	Variable	Not known

 

Candida auris

C. auris was first isolated in 2009 from external ear discharge of a patient from Japan. Since that report, the infection has been reported in South Korea, India, Pakistan and Kuwait. In a recent study of ICU-acquired candidemia in 27 ICUs in India, the pathogen was isolated from 5.2% of 1,400 candidemia cases – the 6th most common isolate – and ranked as the 4th most common isolate in neutropenic patients. The study showed that, before acquiring the infection, a significant number of C. auris candidemia cases underwent invasive interventions, including vascular surgery, total parenteral nutrition, urinary catheterization, post-operative drain and prolonged central venous line days. The duration of ICU stay prior to acquisition of C. auris candidemia was significantly longer (median 25 days, interquartile range [IQR] 12-45 days) than for non-auris candidemia patients (median 15 days, IQR 9-28 days; p<0.001), suggesting nosocomial transmission. However, the exact mode of transmission and source in the hospital environment were not identified.

C. auris is now considered a superbug because of its resistance to azoles and polyenes, and its association with high mortality rates. To combat such a threat, clinicians and microbiologists should heighten vigilance and surveillance for this organism, and improve infection control practices. The agent is not easily identified by phenotypic methods; confirmation would require molecular methods.

Trichosporon species

Of the Trichosporon species, T. asahii is the most common agent causing fungemia, pulmonary and soft tissue infections and meningitis in both immunocompetent and immunosuppressed patients. The majority of invasive infections are associated with malignancies, previous antibiotic therapy, use of a central catheter and admission to ICUs. In Asia, trichosporonosis is the second most common deep-seated yeast infection in China, India, Japan, Taiwan and Thailand. In Thailand, it accounts for 6% of all fungemia cases, with the majority being ICU patients. In Japan, breakthrough infection is common after micafungin therapy and linked to high mortality (76%). In China, the infection commonly affects the urinary system, lungs and blood. Rare Trichosporon species causing infection in Asia include T. dermatis, T. inkin, T. montevideense, T. asteroides, T. faecale, T. ovoides, T. domesticum, T. japonicum and T. jirovecii. The high mortality from trichosporonosis is due to delay in identifying the causative agent and poor susceptibility to antifungal agents.

Conclusion

Asian countries harbor a wide spectrum of new yeasts that are potentially pathogenic in susceptible hosts. The emergence of multidrug-resistant C. auris infection and trichosporonosis is a matter of serious concern. There is an urgent need to work on awareness of clinicians, improvement of mycology laboratory facilities, and bridging gaps in infection control practices in the region.

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