Elizabeth L. Berkow

Simultaneous Emergence of Multidrug-Resistant Candida auris on 3 Continents Confirmed by Whole-Genome Sequencing and Epidemiological Analyses

Background. Candida auris, a multidrug-resistant yeast that causes invasive infections, was first described in 2009 in Japan and has since been reported from several countries. Methods. To understand the global emergence and epidemiology of C. auris, we obtained isolates from 54 patients with C. auris infection from Pakistan, India, South Africa, and Venezuela during 2012–2015 and the type specimen from Japan. Patient information was available for 41 of the isolates. We conducted antifungal susceptibility testing and whole-genome sequencing (WGS). Results. Available clinical information revealed that 41% of patients had diabetes mellitus, 51% had undergone recent surgery, 73% had a central venous catheter, and 41% were receiving systemic antifungal therapy when C. auris was isolated. The median time from admission to infection was 19 days (interquartile range, 9–36 days), 61% of patients had bloodstream infection, and 59% died. Using stringent break points, 93% of isolates were resistant to fluconazole, 35% to amphotericin B, and 7% to echinocandins; 41% were resistant to 2 antifungal classes and 4% were resistant to 3 classes. WGS demonstrated that isolates were grouped into unique clades by geographic region. Clades were separated by thousands of single-nucleotide polymorphisms, but within each clade isolates were clonal. Different mutations in ERG11 were associated with azole resistance in each geographic clade. Conclusions. C. auris is an emerging healthcare-associated pathogen associated with high mortality. Treatment options are limited, due to antifungal resistance. WGS analysis suggests nearly simultaneous, and recent, independent emergence of different clonal populations on 3 continents. Risk factors and transmission mechanisms need to be elucidated to guide control measures.

Notes from the Field: Ongoing Transmission of Candida auris in Health Care Facilities — United States, June 2016–May 2017

Ongoing Transmission of Candida auris in Health Care Facilities — United States, June 2016–May 2017 Sharon Tsay, MD1,2; Rory M. Welsh, PhD1; Eleanor H. Adams, MD3; Nancy A. Chow, PhD1; Lalitha Gade, MPharm1; Elizabeth L. Berkow, PhD1; Eugenie Poirot, PhD2,4; Emily Lutterloh, MD3,5; Monica Quinn, MS3; Sudha Chaturvedi, PhD3,5; Janna Kerins, VMD2,6; Stephanie R. Black, MD6; Sarah K. Kemble, MD6; Patricia M. Barrett, MSD7; Kerri Barton, MPH8; D.J. Shannon, MPH9; Kristy Bradley, DVM10; Shawn R. Lockhart, PhD1; Anastasia P. Litvintseva, PhD1; Heather MoultonMeissner, PhD11; Alicia Shugart, MA11; Alex Kallen, MD11; Snigdha Vallabhaneni, MD1; Tom M. Chiller, MD1; Brendan R. Jackson, MD1

Isolation of Candida auris from 9 patients in Central America: Importance of accurate diagnosis and susceptibility testing

Candida auris is an emerging multidrug‐resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing.

In Vitro Activity of a Novel Glucan Synthase Inhibitor, SCY-078, against Clinical Isolates of Candida auris

Candida auris, an emerging fungal pathogen that is associated with high mortality, has been identified in many countries across the world. It is often mistaken for other Candida species in the clinical laboratory and has shown a marked ability to withstand standard infection control practices. More

Changes in the epidemiological landscape of invasive candidiasis

The epidemiology of invasive candidiasis has evolved in recent years, warranting a review of the changes and the implications for current and future diagnosis and treatment. The overall burden of invasive candidiasis remains high, particularly in the expanding populations of patients at risk of opportunistic infection, such as the elderly or immunosuppressed. Progressive shifts from Candida albicans to non-albicans Candida spp. have been observed globally. The recent emergence of novel, multiresistant species, such as Candida auris, amplifies the call for vigilance in detection and advances in treatment. Among the current treatment options, fluconazole is still widely used throughout the world. Increased resistance to fluconazole, both acquired and naturally emerging, has been observed. Resistance to echinocandins is presently low but this may change with increased use. Improvement of diagnostic techniques and strategies, development of international surveillance networks and implementation of antifungal stewardship programmes represent major challenges for a better epidemiological control of invasive candidiasis.

Fluconazole resistance in Candida species: a current perspective

Candida albicans and the emerging non-albicans Candida spp. have significant clinical relevance among many patient populations. Current treatment guidelines include fluconazole as a primary therapeutic option for the treatment of these infections, but it is only fungistatic against Candida spp. and both inherent and acquired resistance to fluconazole have been reported. Such mechanisms of resistance include increased drug efflux, alteration or increase in the drug target, and development of compensatory pathways for producing the target sterol, ergosterol. While many mechanisms of resistance observed in C. albicans are also found in the non-albicans species, there are also important and unexpected differences between species. Furthermore, mechanisms of fluconazole resistance in emerging Candida spp., including the global health threat Candida auris, are largely unknown. In order to preserve the utility of one of our fundamental antifungal drugs, fluconazole, it is essential that we fully appreciate the manner by which Candida spp. manifest resistance to it.

Candida auris for the Clinical Microbiology Laboratory: Not Your Grandfather's Candida Species

Candida auris is a newly emerging species that was first identified in Asia in 2009 but has rapidly spread across the world. C. auris differs from most other Candida species in that antifungal resistance is the norm rather than the exception, it is a commensal of human skin rather than the human gut, and it can be easily transmitted from person to person in a healthcare setting. This review discusses the emergence of C. auris, global epidemiology, identification, antifungal susceptibility testing, and precautions to be taken when it is identified from a patient specimen.

Isolation of azole-resistant Aspergillus fumigatus from the environment in the south-eastern USA

Background: Azole resistance in isolates of the fungus Aspergillus fumigatus has been associated with agricultural use of azole fungicides. Environmental isolation of resistant isolates has been reported in Asia, Africa, Europe and South America. Objectives: To determine whether A. fumigatus isolates containing TR34/L98H or TR46/Y121F/T289A can be found in fields in the USA treated with agricultural azoles. Methods: Crop debris was collected and screened for A. fumigatus. All A. fumigatus isolates were screened for azole resistance. The CYP51A gene of azole‐resistant isolates was sequenced. The population structure of a subset of isolates was determined using microsatellite typing. Results: This article identifies azole‐resistant A. fumigatus isolates containing the TR34/L98H mutation in an experimental peanut field that had been treated with azole fungicides. Conclusions: These findings suggest the development of resistance to azole antifungals in A. fumigatus may be present where agricultural azoles are used in the USA.

Activity of CD101, a long-acting echinocandin, against clinical isolates of Candida auris

CD101 is a new echinocandin with a prolonged half-life. CD101 was tested by broth microdilution against 100 isolates of the emerging yeast Candida auris. It showed activity against most isolates, including some that were resistant to other echinocandins.

Ceragenins are active against drug-resistant Candida auris clinical isolates in planktonic and biofilm forms

Background Candida auris has emerged as a serious threat to human health. Of particular concern are the resistance profiles of many clinical isolates, with some being resistant to multiple classes of antifungals. Objectives Measure susceptibilities of C. auris isolates, in planktonic and biofilm forms, to ceragenins (CSAs). Determine the effectiveness of selected ceragenins in gel and cream formulations in eradicating fungal infections in tissue explants. Materials and methods A collection of 100 C. auris isolates available at CDC was screened for susceptibility to a lead ceragenin. A smaller collection was used to characterize antifungal activities of other ceragenins against organisms in planktonic and biofilm forms. Effects of ceragenins on fungal cells and biofilms were observed via microscopy. An ex vivo model of mucosal fungal infection was used to evaluate formulated forms of lead ceragenins. Results Lead ceragenins displayed activities comparable to those of known antifungal agents against C. auris isolates with MICs of 0.5-8 mg/L and minimum fungicidal concentrations (MFCs) of 2-64 mg/L. No cross-resistance with other antifungals was observed. Fungal cell morphology was altered in response to ceragenin treatment. Ceragenins exhibited activity against sessile organisms in biofilms. Gel and cream formulations including 2% CSA-44 or CSA-131 resulted in reductions of over 4 logs against established fungal infections in ex vivo mucosal tissues. Conclusions Ceragenins demonstrated activity against C. auris, suggesting that these compounds warrant further study to determine whether they can be used for topical applications to skin and mucosal tissues for treatment of infections with C. auris and other fungi.