scholarly journals Delineation of the Direct Contribution of Candida auris ERG11 Mutations to Clinical Triazole Resistance

2021 ◽  
Author(s):  
Jeffrey M. Rybak ◽  
Cheshta Sharma ◽  
Laura A. Doorley ◽  
Katherine S. Barker ◽  
Glen E. Palmer ◽  
...  
Keyword(s):  
Health Care ◽  
Antifungal Agents ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Direct Contribution ◽  
Clinical Concern

Candida auris is an emerging multidrug-resistant and health care-associated pathogen of urgent clinical concern. The triazoles are the most widely prescribed antifungal agents worldwide and are commonly utilized for the treatment of invasive Candida infections.

scholarly journals Survival, Persistence, and Isolation of the Emerging Multidrug-Resistant Pathogenic Yeast Candida auris on a Plastic Health Care Surface

2017 ◽  
Vol 55 (10) ◽  
pp. 2996-3005 ◽  
Author(s):  
Rory M. Welsh ◽  
Meghan L. Bentz ◽  
Alicia Shams ◽  
Hollis Houston ◽  
Amanda Lyons ◽  
...  
Keyword(s):  
Health Care ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Pathogenic Yeast ◽  
Content Type ◽  
Health Care Settings ◽  
Care Facilities ◽  
Enrichment Protocol ◽  
Plastic Surfaces

ABSTRACTThe emerging multidrug-resistant pathogenic yeastCandida aurisrepresents a serious threat to global health. Unlike most otherCandidaspecies, this organism appears to be commonly transmitted within health care facilities and causes health care-associated outbreaks. To better understand the epidemiology of this emerging pathogen, we investigated the ability ofC. auristo persist on plastic surfaces common in health care settings compared with that ofCandida parapsilosis, a species known to colonize the skin and plastics. Specifically, we compiled comparative and quantitative data essential to understanding the vehicles of spread and the ability of both species to survive and persist on plastic surfaces under controlled conditions (25°C and 57% relative humidity), such as those found in health care settings. When a test suspension of 104cells was applied and dried on plastic surfaces,C. aurisremained viable for at least 14 days andC. parapsilosisfor at least 28 days, as measured by CFU. However, survival measured by esterase activity was higher forC. auristhanC. parapsilosisthroughout the 28-day study. Given the notable length of timeCandidaspecies survive and persist outside their host, we developed methods to more effectively cultureC. aurisfrom patients and their environment. Using our enrichment protocol, public health laboratories and researchers can now readily isolateC. aurisfrom complex microbial communities (such as patient skin, nasopharynx, and stool) as well as environmental biofilms, in order to better understand and preventC. auriscolonization and transmission.

scholarly journals Abrogation of Triazole Resistance upon Deletion of CDR1 in a Clinical Isolate of Candida auris

2019 ◽  
Vol 63 (4) ◽  
Author(s):  
Jeffrey M. Rybak ◽  
Laura A. Doorley ◽  
Andrew T. Nishimoto ◽  
Katherine S. Barker ◽  
Glen E. Palmer ◽  
...  
Keyword(s):  
Health Care ◽  
Clinical Isolate ◽  
Reference Strain ◽  
Multidrug Resistant ◽  
Clinical Isolates ◽  
Candida Auris ◽  
Content Type ◽  
Genetic Manipulations ◽  
Global Concern ◽  
First Time

ABSTRACT Candida auris has rapidly emerged as a health care-associated and multidrug-resistant pathogen of global concern. In this work, we examined the relative expression of the four C. auris genes with the highest degree of homology to Candida albicans CDR1 and MDR1 among three triazole-resistant clinical isolates as compared to the triazole-susceptible genome reference clinical isolate. We subsequently utilized a novel Cas9-mediated system for genetic manipulations to delete C. auris CDR1 and MDR1 in both a triazole-resistant clinical isolate and a susceptible reference strain and observed that MICs for all clinically available triazoles decreased as much as 128-fold in the CDR1 deletion strains. The findings of this work reveal for the first time that C. auris CDR1 and MDR1 are more highly expressed among triazole-resistant clinical isolates of C. auris and that the overexpression of CDR1 is a significant contributor to clinical triazole resistance.

scholarly journals Development and Validation of a Real-Time PCR Assay for Rapid Detection of Candida auris from Surveillance Samples

2017 ◽  
Vol 56 (2) ◽  
Author(s):  
L. Leach ◽  
Y. Zhu ◽  
S. Chaturvedi
Keyword(s):  
Health Care ◽  
Real Time ◽  
Real Time Pcr ◽  
Multidrug Resistant ◽  
Effective Control ◽  
Pcr Assay ◽  
Candida Auris ◽  
Content Type ◽  
The Real ◽  
Positive Results

ABSTRACT Candida auris is an emerging multidrug-resistant yeast causing invasive health care-associated infection with high mortality worldwide. Rapid identification of C. auris is of primary importance for the implementation of public health measures to control the spread of infection. To achieve these goals, we developed and validated a TaqMan-based real-time PCR assay targeting the internal transcribed spacer 2 (ITS2) region of the ribosomal gene. The assay was highly specific, reproducible, and sensitive, with the detection limit of 1 C. auris CFU/PCR. The performance of the C. auris real-time PCR assay was evaluated by using 623 surveillance samples, including 365 patient swabs and 258 environmental sponges. Real-time PCR yielded positive results from 49 swab and 58 sponge samples, with 89% and 100% clinical sensitivity with regard to their respective culture-positive results. The real-time PCR also detected C. auris DNA from 1% and 12% of swab and sponge samples with culture-negative results, indicating the presence of dead or culture-impaired C. auris. The real-time PCR yielded results within 4 h of sample processing, compared to 4 to 14 days for culture, reducing turnaround time significantly. The new real-time PCR assay allows for accurate and rapid screening of C. auris and can increase effective control and prevention of this emerging multidrug-resistant fungal pathogen in health care facilities.

scholarly journals Candida auris: an Emerging Fungal Pathogen

2017 ◽  
Vol 56 (2) ◽  
Author(s):  
Emily S. Spivak ◽  
Kimberly E. Hanson
Keyword(s):  
Health Care ◽  
Fungal Pathogen ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Environmental Persistence ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Hospital Infection Control ◽  
Skin Colonization

ABSTRACT Candida auris has emerged globally as a multidrug-resistant health care-associated fungal pathogen. Recent reports highlight ongoing challenges due to organism misidentification, high rates of antifungal drug resistance, and significant patient mortality. The predilection for transmission within and between health care facilities possibly promoted by virulence factors that facilitate skin colonization and environmental persistence is unique among Candida species. This minireview details the global emergence of C. auris and discusses issues relevant to clinical microbiology laboratories, hospital infection control, and antimicrobial stewardship efforts.

scholarly journals Candida auris Biofilm Colonization on Skin Niche Conditions

mSphere ◽  
2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Priya Uppuluri
Keyword(s):  
Health Care ◽  
Ex Vivo ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Biofilm Growth ◽  
Content Type ◽  
Care Facilities ◽  
Invasive Infections ◽  
Skin Conditions

ABSTRACT Candida auris, an emerging multidrug-resistant yeast, has recently been associated with outbreaks of invasive infections in health care facilities worldwide. Its success as a nosocomial pathogen lies in its capability to sustain for prolonged periods in the intensive care unit (ICU), adeptly colonize skin, and spread among patients. Little is known of the mechanism behind the predilection of C. auris for skin or the extent of its resilience on it. Now, M. V. Horton, C. J. Johnson, J. F. Kernien, T. D. Patel, et al. (mSphere 5:e00910-19, 2020, https://doi.org/10.1128/mSphere.00910-19) demonstrate that in synthetic sweat medium designed to mimic axillary skin conditions, C. auris can grow into multilayers of cells called biofilms that can resist desiccation. C. auris’ propensity to form biofilms was further elaborated using a novel ex vivo porcine skin model of skin colonization. These studies provide early evidence that C. auris biofilm cells persisting on skin could serve as source of continuing outbreaks in health care facilities. Interventions blocking C. auris biofilm growth on skin will help control the spread of this pathogen.

scholarly journals Environmental Isolation of Candida auris from the Coastal Wetlands of Andaman Islands, India

mBio ◽  
2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Parth Arora ◽  
Prerna Singh ◽  
Yue Wang ◽  
Anamika Yadav ◽  
Kalpana Pawar ◽  
...  
Keyword(s):  
Salt Marsh ◽  
Coastal Wetlands ◽  
Ecological Niche ◽  
Multidrug Resistant ◽  
Sandy Beaches ◽  
Andaman Islands ◽  
Human Pathogen ◽  
Candida Auris ◽  
Content Type ◽  
The Indian Ocean

ABSTRACT Candida auris is a multidrug resistant pathogen that presents a serious global threat to human health. As C. auris is a newly emerged pathogen, several questions regarding its ecological niche remain unexplored. While species closely related to C. auris have been detected in different environmental habitats, little is known about the natural habitat(s) of C. auris. Here, we explored the virgin habitats around the very isolated Andaman Islands in the Indian Ocean for evidence of C. auris. We sampled coastal wetlands, including rocky shores, sandy beaches, tidal marshes, and mangrove swamps, around the Andaman group of the Andaman & Nicobar Islands, Union Territory, in India. Forty-eight samples of sediment soil and seawater were collected from eight sampling sites representing the heterogeneity of intertidal habitats across the east and west coast of South Andaman district. C. auris was isolated from two of the eight sampling sites, a salt marsh and a sandy beach. Interestingly, both multidrug-susceptible and multidrug-resistant C. auris isolates were found in the sample. Whole-genome sequencing analysis clustered the C. auris isolates into clade I, showing close similarity to other isolates from South Asia. Isolation of C. auris from the tropical coastal environment suggests its association with the marine ecosystem. The fact that viable C. auris was detected in the marine habitat confirms C. auris survival in harsh wetlands. However, the ecological significance of C. auris in salt marsh wetland and sandy beaches to human infections remains to be explored. IMPORTANCE Candida auris is a recently emerged multidrug-resistant fungal pathogen capable of causing severe infections in hospitalized patients. Despite its recognition as a human pathogen a decade ago, so far the natural ecological niche(s) of C. auris remains enigmatic. A previous hypothesis suggested that C. auris might be native to wetlands, that its emergence as a human pathogen might have been linked to global warming effects on wetlands, and that its enrichment in that ecological niche was favored by the ability of C. auris for thermal tolerance and salinity tolerance. To understand the mystery of environmental niches of C. auris, we explored the coastal wetland habitat around the very isolated Andaman Islands in the Indian Ocean. C. auris was isolated from the virgin habitats of salt marsh area with no human activity and from a sandy beach. C. auris isolation from the marine wetlands suggests that prior to its recognition as a human pathogen, it existed as an environmental fungus.

scholarly journals In Vitro Antifungal Combination of Flucytosine with Amphotericin B, Voriconazole, or Micafungin against Candida auris Shows No Antagonism

2019 ◽  
Vol 63 (12) ◽  
Author(s):  
A. L. Bidaud ◽  
F. Botterel ◽  
A. Chowdhary ◽  
E. Dannaoui
Keyword(s):  
Amphotericin B ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Resistant Mutants ◽  
Hospital Acquired

ABSTRACT Candida auris is an emerging, multidrug-resistant pathogen responsible for invasive hospital-acquired infections. Flucytosine is an effective anti-Candida species drug, but which cannot be used as a monotherapy because of the risk of development of resistant mutants during treatment. It is, therefore, noteworthy to test possible combinations with flucytosine that may have a synergistic interaction. In this study, we determined the in vitro interaction between flucytosine and amphotericin B, micafungin, or voriconazole. These combinations have been tested against 15 C. auris isolates. The MIC ranges (geometric mean [Gmean]) of flucytosine, amphotericin B, micafungin, and voriconazole were 0.125 to 1 μg/ml (0.42 μg/ml), 0.25 to 1 μg/ml (0.66 μg/ml), 0.125 to 0.5 μg/ml (0.3 μg/ml), and 0.03 to 4 μg/ml (1.05 μg/ml), respectively. When tested in combination, indifferent interactions were mostly observed with fractional inhibitory concentration index values from 0.5 to 1, 0.31 to 1.01, and 0.5 to 1.06 for the combinations of flucytosine with amphotericin B, micafungin, and voriconazole, respectively. A synergy was observed for the strain CBS 10913 from Japan. No antagonism was observed for any combination. The combination of flucytosine with amphotericin B or micafungin may be relevant for the treatment of C. auris infections.

scholarly journals Simultaneous Infection with Enterobacteriaceae and Pseudomonas aeruginosa Harboring Multiple Carbapenemases in a Returning Traveler Colonized with Candida auris

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Ayesha Khan ◽  
William C. Shropshire ◽  
Blake Hanson ◽  
An Q. Dinh ◽  
Audrey Wanger ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Susceptibility Testing ◽  
Multidrug Resistant ◽  
Critically Ill Patient ◽  
Whole Genome ◽  
Candida Auris ◽  
Content Type ◽  
Simultaneous Infection ◽  
Polymicrobial Infections ◽  
Selection Of

ABSTRACT We report our clinical experience treating a critically ill patient with polymicrobial infections due to multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa in a 56-year-old woman who received health care in India and was also colonized by Candida auris. A precision medicine approach using whole-genome sequencing revealed a multiplicity of mobile elements associated with NDM-1, NDM-5, and OXA-181 and, supplemented with susceptibility testing, guided the selection of rational antimicrobial therapy.

scholarly journals Vaccine Protection against Multidrug-Resistant Klebsiella pneumoniae in a Nonhuman Primate Model of Severe Lower Respiratory Tract Infection

mBio ◽  
2019 ◽  
Vol 10 (6) ◽  
Author(s):  
Natalia Malachowa ◽  
Scott D. Kobayashi ◽  
Adeline R. Porter ◽  
Brett Freedman ◽  
Patrick W. Hanley ◽  
...  
Keyword(s):  
United States ◽  
Risk Factors ◽  
Health Care ◽  
Lower Respiratory Tract ◽  
The United States ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Content Type ◽  
Carbapenem Resistant ◽  
Cynomolgus Macaques

ABSTRACT Klebsiella pneumoniae is a human gut communal organism and notorious opportunistic pathogen. The relative high burden of asymptomatic colonization by K. pneumoniae is often compounded by multidrug resistance—a potential problem for individuals with significant comorbidities or other risk factors for infection. A carbapenem-resistant K. pneumoniae strain classified as multilocus sequence type 258 (ST258) is widespread in the United States and is usually multidrug resistant. Thus, treatment of ST258 infections is often difficult. Inasmuch as new preventive and/or therapeutic measures are needed for treatment of such infections, we developed an ST258 pneumonia model in cynomolgus macaques and tested the ability of an ST258 capsule polysaccharide type 2 (CPS2) vaccine to moderate disease severity. Compared with sham-vaccinated animals, those vaccinated with ST258 CPS2 had significantly less disease as assessed by radiography 24 h after intrabronchial installation of 108 CFU of ST258. All macaques vaccinated with CPS2 ultimately developed ST258-specific antibodies that significantly enhanced serum bactericidal activity and killing of ST258 by macaque neutrophils ex vivo. Consistent with a protective immune response to CPS2, transcripts encoding inflammatory mediators were increased in infected lung tissues obtained from CPS-vaccinated animals compared with control, sham-vaccinated macaques. Taken together, our data provide support for the idea that vaccination with ST258 CPS can be used to prevent or moderate infections caused by ST258. As with studies performed decades earlier, we propose that this prime-boost vaccination approach can be extended to include multiple capsule types. IMPORTANCE Multidrug-resistant bacteria continue to be a major problem worldwide, especially among individuals with significant comorbidities and other risk factors for infection. K. pneumoniae is among the leading causes of health care-associated infections, and the organism is often resistant to multiple classes of antibiotics. A carbapenem-resistant K. pneumoniae strain known as multilocus sequence type 258 (ST258) is the predominant carbapenem-resistant Enterobacteriaceae in the health care setting in the United States. Infections caused by ST258 are often difficult to treat and new prophylactic measures and therapeutic approaches are needed. To that end, we developed a lower respiratory tract infection model in cynomolgus macaques in which to test the ability of ST258 CPS to protect against severe ST258 infection.

scholarly journals Identification of Candida auris by Use of the Updated Vitek 2 Yeast Identification System, Version 8.01: a Multilaboratory Evaluation Study

2019 ◽  
Vol 57 (11) ◽  
Author(s):  
Georges Ambaraghassi ◽  
Philippe J. Dufresne ◽  
Simon F. Dufresne ◽  
Émilie Vallières ◽  
José F. Muñoz ◽  
...  
Keyword(s):  
Evaluation Study ◽  
Multidrug Resistant ◽  
Identification System ◽  
Correct Identification ◽  
South American ◽  
The South ◽  
Candida Auris ◽  
Yeast Identification ◽  
Content Type ◽  
Vitek 2

ABSTRACT Candida auris is an emerging multidrug-resistant yeast that has been systematically incorrectly identified by phenotypic methods in clinical microbiology laboratories. The Vitek 2 automated identification system (bioMérieux) recently included C. auris in its database (version 8.01). We evaluated the performance of the Vitek 2 YST ID card to identify C. auris and related species. A panel of 44 isolates of Candida species (C. auris, n = 35; Candida haemulonii, n = 5; Candida duobushaemulonii, n = 4) were tested by three different hospital-based microbiology laboratories. Among 35 isolates of C. auris, Vitek 2 yielded correct identification in an average of 52% of tested samples. Low-discrimination (LD) results with an inability to distinguish between C. auris, C. duobushaemulonii, and Candida famata were obtained in an average of 27% of samples. Incorrect identification results were obtained in an average of 21% of samples, the majority (91%) of which were reported as C. duobushaemulonii and the remaining 9% of which were reported as Candida lusitaniae/C. duobushaemulonii. The proportion of correct identification was not statistically different across different centers (P = 0.78). Stratification by genetic clades demonstrated that 100% (n = 8) of the strains of the South American clade were correctly identified compared to 7% (n = 10) and 0% (n = 4) from the African and East Asian clades, respectively. None of the non-auris Candida strains (n = 9) were incorrectly identified as C. auris. Our results show that the Vitek 2 (version 8.01) yeast identification system has a limited ability to correctly identify C. auris. These data suggest that an identification result for C. duobushaemulonii should warrant further testing to rule out C. auris. The overall performance of the Vitek 2 seems to differ according to C. auris genetic clade, with the South American isolates yielding the most accurate results.

Sign in / Sign up

Export Citation Format

Share Document