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Candida auris: An Emerging Fungal Infectious Disease

Amesh A. Adalja, MD, FACP, FACEP, FIDSA, November 4, 2016

When the topic of multiple-drug-resistant infections is discussed, it is often limited to bacterial agents, with little to no discussion of the resistance of infectious agents other than bacteria. However, as has been well documented, resistance is a universal feature of microbial life. Infections of antiviral-resistant HIV and influenza are substantial threats. A detailed report from the Centers for Disease Control and Prevention (CDC), published in Clinical Infectious Diseases, reinforces the impact of nonbacterial agent resistance.1 In this report, Lockhart and colleagues document the multinational emergence of the often drug-resistant fungal pathogen Candida auris.

 

Pakistani Outbreak Led to Heightened Interest

While Candida infections are exceedingly common, those caused by C. auris are not. The fungus was first described as an etiologic agent in human disease in 2009 (and the first retrospective case dates to 1996), but it was a 2015 outbreak in Pakistan that prompted highened attention. This outbreak, combined with simultaneous cases in South Africa, Venezuela, and India, led to an international collaboration to gain more insight into this fungus and its role in human disease.

As part of this collaboration, isolates and case histories were sought from 54 patients from the 4 nations with C. auris cases. Important details about case patients included:

  • The median age of patients was 54. 
  • Diabetes mellitus was the most common comorbid condition present.
  • Half of all patients had had a surgical procedure in the 90 days preceding infection.
  • A central venous catheter was present in 78%; a urinary catheter was present in 61%.
  • The overall mortality rate was 59%, and it was 68% in those with bloodstream infections.

Strikingly notable was the amount of drug resistance, with 93% resistant to fluconazole, 54% resistant to voriconazole, 35% resistant to amphotericin B, 7% resistant to echinocandins, and 6% resistant to flucytosine. Ominously, 41% of isolates were resistant to at least 2 classes of antifungals. Whole genome sequencing revealed 4 distinct clades but also revealed a cluster of almost identical strains connected to one hospital in Pakistan. A query of the international SENTRY surveillance database, which contains more than 15,000 Candida isolates, revealed 4 C. auris isolatesall from 2009 or later.

 

International Call to Arms

The emergence of C. auris—with its attendant mortality, high rates of drug resistance, and international presence—is, as my colleagues at the University of Pittsburgh Clancy and Nguyen note in an accompanying editorial, an “international call to arms.”2 In fact, although no cases have yet appeared in the US, the CDC has issued an alert on the pathogen, which has caused further outbreaks in England and Israel and has alarmingly been found to account for more than 5% of candidemia cases in Indian ICUs.

Important scientific work remains to be performed to meet the challenges posed by C. auris, including understanding the elements that led to its recent emergence as well as identifying the best treatment and infection control strategies needed to contain its spread and limit the damage it may cause.

 

References

  1. Lockhart SR, Etienne KA, Vallabhaneni S, et al. Simultaneous emergence of multidrug resistant Candida auris on three continents confirmed by whole genome sequencing and epidemiological analyses. Clin Infect Dis 2016; http://cid.oxfordjournals.org/content/early/2016/10/20/cid.ciw691.abstract. Accessed November 2, 2016.
  2. Clancy CJ, Nguyen MH. Emergence of Candida auris: an international call-to-arms. Clin Infect Dis 2016; http://cid.oxfordjournals.org/content/early/2016/10/20/cid.ciw696.full.pdf+html. Accessed November 2, 2016.