Candida auris, an emerging health care-associated fungus, has limited treatment options due to widespread antifungal resistance and is associated with high mortality rates, according to research published in Clinical Infectious Diseases.
“[Candida (C.) auris] can be a challenge to identify and treat, especially in resource-limited settings, where molecular identification may not be immediately available and access to antifungals other than fluconazole may be limited,” Shawn R. Lockhart, PhD, D(ABMM), from the mycotic diseases branch of the CDC, and colleagues wrote. “An international collaboration was established to better understand the epidemiology of C. auris and to determine the extent of resistance and whether the emergence of this organism was occurring independently in multiple countries or was caused by the spread of a single outbreak strain.”
C. auris was first described in Japan in 2009. Lockhart and colleagues reported that C. auris has been identified in Asia, Africa and South America; however, the fungus has since expanded to North America, according to more recent CDC data.
In this study, the researchers described the clinical characteristics of patients with C. auris infection, antifungal susceptibility patterns and whole genome sequences (WGS) of C. auris isolates. They examined 41 isolates obtained from 54 patients with C. auris from Pakistan, India, South Africa, and Venezuela who were infected from 2012 to 2015. The researchers also analyzed the type specimen from Japan to better understand the global emergence and epidemiology of the pathogen.
Among patients with C. auris infection, 61% had bloodstream infections (BSIs), 41% had diabetes mellitus, 51% had recent surgery, 78% had a central venous catheter, and 41% were receiving systemic antifungal therapy. The median duration from admission to diagnosis was 19 days. Overall, 59% patients died, including 68% with BSIs and 71% with urinary tract infections who most likely died from associated sepsis, according to the researchers.
“Because of the seriousness of the underlying disease of many of the patients, attributable mortality could not be determined,” they wrote.
During susceptibility testing, Lockhart and colleagues found that 93% of C. auris isolates were resistant to fluconazole, 35% were resistant to amphotericin B, and 7% were resistant to echinocandins. In addition, 41% of isolates had resistance against two antifungal classes, and two isolates had resistance against three classes.
A WGS analysis revealed that isolates were grouped into unique clades, separated by thousands of single nucleotide polymorphisms, that varied by geographical region. In each clade, the isolates were clonal.
Lockhart and colleagues compared Erg11 amino acid sequences of C. auris with those of Candida albicans. They discovered that nine amino acid substitutions that have been identified in resistant C. albicans isolates were present in all C. auris isolates. In addition, three other ERG11 mutations that have been suspected or confirmed to increase fluconazole resistance in C. albicans were identified in each geographic clade.
“Multidrug resistance and high associated mortality makes C. auris an emerging global threat,” Lockhart and colleagues concluded. “There are still many unanswered questions about C. auris including why it has suddenly emerged, whether its clonal expansion and global distribution will level off or continue, how it is transmitted, and what infection prevention and control measures are needed to prevent its spread within hospitals.”
In a related editorial, Cornelius J. Clancy, MD, of the department of medicine at the University of Pittsburgh, called for international efforts to contain C. auris before the pathogen further spreads. He suggested that the “immediate priorities” of such efforts include more research on the epidemiology, ecology, evolution, resistance mechanisms, treatment and prevention of C. auris.
“We are living in an era in which fungal diseases are causing unprecedented damage to animals, plants and ecosystems,” he wrote. “The C. auris story is another reminder that humans will not be spared from emerging mycoses.” – by Savannah Demko
Disclosure: The researchers report no relevant financial disclosures.