Antifungal Resistance Trends of Candida auris Clinical Isolates, New York-New Jersey, 2016-2020

2022 ◽  
Author(s):  
Shannon Kilburn ◽  
Gabriel Innes ◽  
Monica Quinn ◽  
Karen Southwick ◽  
Belinda Ostrowsky ◽  
...  
Keyword(s):  
New York ◽  
New Jersey ◽  
Amphotericin B ◽  
Regional Differences ◽  
Antifungal Resistance ◽  
Clinical Isolates ◽  
Candida Auris ◽  
Fluconazole Resistant ◽  
Echinocandin Resistance ◽  
Clinical Cases

About 55% of U.S. Candida auris clinical cases were reported from New York and New Jersey from 2016 through 2020. Nearly all New York-New Jersey clinical isolates (99.8%) were fluconazole resistant, and 50% were amphotericin B resistant. Echinocandin resistance increased from 0% to 4% and pan-resistance increased from 0 to <1% for New York C. auris clinical isolates but not for New Jersey, highlighting the regional differences.

scholarly journals Categorizing susceptibility of clinical isolates of Candida auris to amphotericin B, caspofungin, and fluconazole utilizing the CLSI M44-A2 disk diffusion method

2021 ◽  
Author(s):  
Natalie S. Nunnally ◽  
Tajah Damm ◽  
Shawn R. Lockhart ◽  
Elizabeth L. Berkow
Keyword(s):  
Amphotericin B ◽  
Accurate Method ◽  
Clinical Isolates ◽  
Disk Diffusion ◽  
Diffusion Method ◽  
Broth Microdilution ◽  
Candida Auris ◽  
Disk Diffusion Method ◽  
Microdilution Method ◽  
Broth Microdilution Method

We evaluated the CLSI M44ed3E disk diffusion method in comparison with the CLSI M27ed4 broth microdilution method for caspofungin and fluconazole and the Etest method for amphotericin B to categorize susceptibility of 347 clinical isolates of Candida auris. Utilizing the zone diameter cutoffs established here we observed the overall categorial agreement between the two methods. For caspofungin, concordant results were observed for 98% of isolates with <1% very major and 1% major errors. For fluconazole, concordant results were observed for 91% of isolates with 1% very major and 8% major errors. For amphotericin B, concordant results were observed for 74% of isolates with <1% very major errors and 25% major errors. The disk diffusion approach provides an accurate method for determining the susceptibility of C. auris for caspofungin and fluconazole, and for identification of at least 75% of amphotericin B-susceptible isolates.

scholarly journals Multi-omics Signature of Candida auris, an Emerging and Multidrug-Resistant Pathogen

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Daniel Zamith-Miranda ◽  
Heino M. Heyman ◽  
Levi G. Cleare ◽  
Sneha P. Couvillion ◽  
Geremy C. Clair ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Protein Content ◽  
Pathogenic Fungus ◽  
Multidrug Resistant ◽  
Antifungal Resistance ◽  
Clinical Isolates ◽  
Medical Mycology ◽  
Carbon Utilization ◽  
Candida Auris ◽  
Content Type

ABSTRACT Candida auris is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In the present work, we compared two clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans reference strain using a multi-omics approach. Our results show that, despite the distinct drug resistance profile, both C. auris isolates appear to be very similar, albeit with a few notable differences. However, compared to C. albicans both C. auris isolates have major differences regarding their carbon utilization and downstream lipid and protein content, suggesting a multifactorial mechanism of drug resistance. The molecular profile displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of this new emerging pathogen. IMPORTANCE Candida auris was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of C. auris differs significantly from C. albicans. In addition to our insights into C. auris carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.

scholarly journals Mutations in TAC1B: a novel genetic determinant of clinical fluconazole resistance in C. auris

2020 ◽  
Author(s):  
Jeffrey M. Rybak ◽  
José F. Muñoz ◽  
Katherine S. Barker ◽  
Josie E. Parker ◽  
Brooke D. Esquivel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Clinical Isolate ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Genetic Determinant ◽  
Candida Auris ◽  
Fluconazole Resistance ◽  
Fluconazole Resistant

ABSTRACTCandida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, the fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro. Comparative analysis of comprehensive sterol profiles, [3H]-fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and the relative expression of C. auris ERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene, TAC1B, and a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into the fluconazole-susceptible isolate AR0387, was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in-vitro, and that mutations in TAC1B significantly contribute to clinical fluconazole resistance.IMPORTANCECandida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrate that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole, and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.

scholarly journals Rare modification in the ergosterol biosynthesis pathway leads to amphotericin B resistance in Candida auris clinical isolates

2021 ◽  
Author(s):  
Milena Kordalewska ◽  
Kevin D. Guerrero ◽  
Timothy D. Mikulski ◽  
Tony N. Elias ◽  
Rocio Garcia-Rubio ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Susceptibility Testing ◽  
Antifungal Susceptibility ◽  
Clinical Isolates ◽  
Resistant Isolate ◽  
Ergosterol Biosynthesis ◽  
Biosynthesis Pathway ◽  
Wild Type ◽  
Candida Auris ◽  
Key Genes

We determined amphotericin B (AmB) susceptibility and sequenced key genes of the ergosterol biosynthesis pathway implicated in AmB resistance (ERG2, ERG3, ERG6, ERG11) of 321 clinical isolates of Candida auris. In antifungal susceptibility testing, 19 (5.9%) isolates were categorized as AmB-resistant (MIC ≥2 mg/l). Only one AmB-resistant isolate presented a unique non-wild-type ERG6 genotype that was confirmed to confer amphotericin B resistance (MIC >32 mg/l) when introduced into a susceptible strain (MIC = 0.5 mg/l).

scholarly journals Antifungal Resistance in Candida auris: Molecular Determinants

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 568
Author(s):  
María Guadalupe Frías-De-León ◽  
Rigoberto Hernández-Castro ◽  
Tania Vite-Garín ◽  
Roberto Arenas ◽  
Alexandro Bonifaz ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Molecular Mechanisms ◽  
Efflux Pumps ◽  
Antifungal Resistance ◽  
Candida Auris ◽  
Fluconazole Resistance ◽  
Online Databases ◽  
Molecular Determinants ◽  
Erg Genes

Since Candida auris integrates strains resistant to multiple antifungals, research has been conducted focused on knowing which molecular mechanisms are involved. This review aims to summarize the results obtained in some of these studies. A search was carried out by consulting websites and online databases. The analysis indicates that most C. auris strains show higher resistance to fluconazole, followed by amphotericin B, and less resistance to 5-fluorocytosine and caspofungin. In C. auris, antifungal resistance to amphotericin B has been linked to an overexpression of several mutated ERG genes that lead to reduced ergosterol levels; fluconazole resistance is mostly explained by mutations identified in the ERG11 gene, as well as a higher number of copies of this gene and the overexpression of efflux pumps. For 5-fluorocytosine, it is hypothesized that the resistance is due to mutations in the FCY2, FCY1, and FUR1 genes. Resistance to caspofungin has been associated with a mutation in the FKS1 gene. Finally, resistance to each antifungal is closely related to the type of clade to which the strain belongs.

scholarly journals Mutations in TAC1B: a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris

mBio ◽  
2020 ◽  
Vol 11 (3) ◽  
Author(s):  
Jeffrey M. Rybak ◽  
José F. Muñoz ◽  
Katherine S. Barker ◽  
Josie E. Parker ◽  
Brooke D. Esquivel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Clinical Isolate ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Genetic Determinant ◽  
Candida Auris ◽  
Fluconazole Resistance ◽  
Content Type ◽  
Fluconazole Resistant

ABSTRACT Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro. Comparative analyses of comprehensive sterol profiles, [3H]fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and relative expression levels of C. auris ERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene TAC1B and to show a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into fluconazole-susceptible isolate AR0387 was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in vitro and that mutations in TAC1B significantly contribute to clinical fluconazole resistance. IMPORTANCE Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris.

scholarly journals Combined Antifungal Resistance and Biofilm Tolerance: the Global Threat of Candida auris

mSphere ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Ryan Kean ◽  
Gordon Ramage
Keyword(s):  
Clinical Importance ◽  
Multidrug Resistant ◽  
Antifungal Resistance ◽  
Antifungal Drugs ◽  
Medical Mycology ◽  
Candida Auris ◽  
Content Type ◽  
Echinocandin Resistance ◽  
Global Threat ◽  
The Impact

ABSTRACT The enigmatic yeast Candida auris has emerged over the last decade and rapidly penetrated our consciousness. The global threat from this multidrug-resistant yeast has generated a call to arms from within the medical mycology community. Over the past decade, our understanding of how this yeast has spread globally, its clinical importance, and how it tolerates and resists antifungal agents has expanded. This review highlights the clinical importance of antifungal resistance in C. auris and explores our current understanding of the mechanisms associated with azole, polyene, and echinocandin resistance. We also discuss the impact of phenotypic tolerance, with particular emphasis on biofilm-mediated resistance, and present new pipelines of antifungal drugs that promise new hope in the management of C. auris infection.

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