scholarly journals Molecular Diagnostics in the Times of Surveillance for Candida auris

2019 ◽  
Vol 5 (3) ◽  
pp. 77 ◽  
Author(s):  
Milena Kordalewska ◽  
David S. Perlin
Keyword(s):  
Dna Amplification ◽  
Antifungal Drugs ◽  
Infection Prevention And Control ◽  
Diagnostic Tools ◽  
Candida Auris ◽  
Accurate Identification ◽  
Healthcare Facilities ◽  
Antifungal Drug Resistance ◽  
The Times ◽  
Almost All

Recently, global health professionals have been significantly challenged by the emergence of Candida auris and its propensity to colonize human skin, persist in the healthcare environment, and cause healthcare-associated outbreaks. Additionally, C. auris isolates are often characterized by elevated minimal inhibitory concentration (MIC) values for antifungal drugs. Thus, rapid detection and accurate identification of C. auris together with an assessment of potential antifungal drug resistance has become essential for effective patient management, and infection prevention and control in healthcare facilities. Surprisingly, almost all of the commonly available diagnostic tools rely on recovery (growth) of yeast colonies from collected samples, which delays the diagnostic result by several days or longer. To circumvent these issues, molecular-based DNA amplification assays have been developed to identify C. auris DNA directly from patient samples. Moreover, allele discriminating detection probes can be used to rapidly assess validated mechanisms of echinocandin and azole resistance.

scholarly journals Preparedness and response to an emerging health threat—Lessons learned from Candida auris outbreaks in the United States

2021 ◽  
pp. 1-6
Author(s):  
Diane Meyer ◽  
Elena K. Martin ◽  
Syra Madad ◽  
Priya Dhagat ◽  
Jennifer B. Nuzzo
Keyword(s):  
United States ◽  
New York ◽  
Qualitative Interviews ◽  
The United States ◽  
Lessons Learned ◽  
Infection Prevention And Control ◽  
Healthcare Organizations ◽  
Candida Auris ◽  
Term Care ◽  
Healthcare Facilities

Abstract Objective: Candida auris infections continue to occur across the United States and abroad, and healthcare facilities that care for vulnerable populations must improve their readiness to respond to this emerging organism. We aimed to identify and better understand challenges faced and lessons learned by those healthcare facilities who have experienced C. auris cases and outbreaks to better prepare those who have yet to experience or respond to this pathogen. Design: Semi-structured qualitative interviews. Setting: Health departments, long-term care facilities, acute-care hospitals, and healthcare organizations in New York, Illinois, and California. Participants: Infectious disease physicians and nurses, clinical and environmental services, hospital leadership, hospital epidemiology, infection preventionists, emergency management, and laboratory scientists who had experiences either preparing for or responding to C. auris cases or outbreaks. Methods: In total, 25 interviews were conducted with 84 participants. Interviews were coded using NVivo qualitative coding software by 2 separate researchers. Emergent themes were then iteratively discussed among the research team. Results: Key themes included surveillance and laboratory capacity, inter- and intrafacility communication, infection prevention and control, environmental cleaning and disinfection, clinical management of cases, and media concerns and stigma. Conclusions: Many of the operational challenges noted in this research are not unique to C. auris, and the ways in which we address future outbreaks should be informed by previous experiences and lessons learned, including the recent outbreaks of C. auris in the United States.

scholarly journals Inactivation of Candida auris and Candida albicans by Ultraviolet-C

2020 ◽  
Vol 41 (S1) ◽  
pp. s292-s292
Author(s):  
William Rutala ◽  
Hajime Kanamori ◽  
Maria Gergen ◽  
Emily Sickbert-Bennett ◽  
David Jay Weber
Keyword(s):  
Infection Prevention ◽  
Antifungal Drugs ◽  
Candida Auris ◽  
Healthcare Facilities ◽  
Environmental Surfaces ◽  
Route Of Transmission ◽  
Indirect Exposure ◽  
Ultraviolet C ◽  
Severe Infections ◽  
Uv C

Background:Candida auris is an emerging fungal pathogen that is often resistant to major classes of antifungal drugs. It is considered a serious global health threat because it has caused severe infections with frequent mortality in over a dozen countries. C. auris can survive on healthcare environmental surfaces for at least 7 days, and it causes outbreaks in healthcare facilities. C. auris has an environmental route of transmission. Thus, infection prevention strategies, such as surface disinfection and room decontamination technologies (eg, ultraviolet [UV-C] light), will be essential to controlling transmission. Unfortunately, data are limited regarding the activity of UV-C to inactivate this pathogen. In this study, a UV-C device was evaluated for its antimicrobial activity against C. auris and C. albicans. Methods: We tested the antifungal activity of a single UV-C device using the vegetative bacteria cycle, which delivers a reflected dose of 12,000 µW/cm2. This testing was performed using Formica sheets (7.6 × 7.6 cm; 3 × 3 inches). The carriers were inoculated with C. auris or C. albicans and placed horizontal on the surface or vertical (ie, perpendicular) to the vertical UV-C lamp and at a distance from 1. 2 m (~4 ft) to 2.4 m (~8 ft). Results: Direct UV-C, with or without FCS (log10 reduction 4.57 and 4.45, respectively), exhibited a higher log10 reduction than indirect UV-C for C. auris (log10 reduction 2.41 and 1.96, respectively), which was statistically significant (Fig. 1 and Table 1). For C. albicans, although direct UV-C had a higher log10 reduction (log10 reduction with and without FCS, 5.26 and 5.07, respectively) compared to indirect exposure (log10 reduction with and without FCS, 3.96 and 3.56, respectively), this difference was not statistically significant. The vertical UV had statistically higher log10 reductions than horizontal UV against C. auris and C. albicans with FCS and without FCS. For example, for C. auris with FCS the log10 reduction for vertical surfaces was 4.92 (95% CI 3.79, 6.04) and for horizontal surfaces the log10 reduction was 2.87 (95% CI, 2.36–3.38). Conclusions:C. auris can be inactivated on environmental surfaces by UV-C as long as factors that affect inactivation are optimized (eg, exposure time). These data and other published UV-C data should be used in developing cycle parameters that prevent contaminated surfaces from being a source of acquisition by staff or patients of this globally emerging pathogen.Funding: NoneDisclosures: None

scholarly journals 1579. Multidrug-Resistant Candida auris Isolates From New York Hospitals and Healthcare Facilities Are Susceptible to Antifungal Combinations

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S576-S577
Author(s):  
Brittany O’Brien ◽  
Sudha Chaturvedi ◽  
Vishnu Chaturvedi
Keyword(s):  
New York ◽  
Diagnostic System ◽  
Multidrug Resistant ◽  
Drug Combinations ◽  
Antifungal Drugs ◽  
Drug Resistant ◽  
Candida Auris ◽  
Current Case ◽  
Healthcare Facilities ◽  
Broth Microdilution Method

Abstract Background Candida auris outbreak continues unabated in New York with the current case counts exceeding 300 patients. We used a modification of standard CLSI broth microdilution method (BMD) if two-drug combinations are efficacious against C. auris isolates with high-resistance to fluconazole (FZ, MIC50 >256 mg/L), and variable resistance to other broad-spectrum antifungal drugs. Methods BMD plates were custom-designed and quality controlled by TREK Diagnostic System. The combination tests of 15 drug-resistant C. auris involved microtiter wells with the initial 144 two-drug combinations and their two-fold dilutions (1/2–1/32) to get 864 two-drug combinations finally. We utilized MIC100 endpoints for the drug combination readings as reported earlier for the intra- and inter-laboratory agreements obtained against Candida species and Aspergillus fumigatus (Antimicrob Agents Chemother. 2015. 59:1759–1766). We also tested minimum fungicidal concentrations (MFC). Results We tested all possible 864 two-drug antifungal combinations for nine antifungal drugs in use to yield 12,960 MIC100 readings, and MFC readings for 15 C. auris isolates. Flucytosine (FLC) at 2.0 mg/L potentiated most successful combinations with other drugs. Micafungin (MFG), Anidulafungin (AFG), Caspofungin (CAS) at individual concentrations of 0.25 mg/L combined well with FLC (2.0 mg/L) to yield MIC100 for 14, 13, and 12 of 15 C. auris isolates tested, respectively. MFG/FLC combination was also fungicidal for 4 of 15 isolates. AMB / FLC (0.25/1.0 mg/L) yielded MIC100 for 13 isolates and MFC for three test isolates. Posaconazole (POS), and Isavuconazole (ISA) and Voriconazole (VRC) also combined well with FLC (0.25/2.0 mg/L) to yield MIC100 for 12, 13, and 13 isolates, respectively. POS/FLC combination was fungicidal for three isolates. Conclusion We identified seven two drug-combinations of antifungals efficacious against drug-resistant C. auris strains. The modified BMD combination susceptibility testing could be used by the clinical laboratories to assist providers with the selection of optimal treatment for C. auris candidemia. Disclosures All authors: No reported disclosures.

scholarly journals Candida auris: a fungus with identity crisis

2020 ◽  
Vol 78 (4) ◽  
Author(s):  
Taissa Vila ◽  
Ahmed S Sultan ◽  
Daniel Montelongo-Jauregui ◽  
Mary Ann Jabra-Rizk
Keyword(s):  
Fungal Species ◽  
Antifungal Drugs ◽  
Multiple Drug ◽  
Rapid Diagnostics ◽  
Contributing Factors ◽  
Candida Auris ◽  
Healthcare Facilities ◽  
Drug Classes ◽  
Recent Emergence ◽  
Robust Response

ABSTRACT Candida auris is a new fungal species that has puzzlingly and simultaneously emerged on five continents. Since its identification in 2009, the scientific community has witnessed an exponential emergence of infection episodes and outbreaks in healthcare facilities world-wide. Candida auris exhibits several concerning features compared to other related Candida species, including persistent colonization of skin and nosocomial surfaces, ability to resist common disinfectants and to spread rapidly among patients. Resistance to multiple drug classes and misidentification by available laboratory identification systems has complicated clinical management, and outcomes of infection have generally been poor with mortality rates approaching 68%. Currently, the origins of C. auris are unclear, and therefore, it is impossible to determine whether environmental and climactic changes were contributing factors in its recent emergence as a pathogen. Nevertheless, a robust response involving rapid diagnostics, prompt interventions and implementation of precautions, are paramount in curtailing the spread of  infections by this fungal species. Importantly, there is a pressing need for the development of new antifungal drugs. In this article, we present a brief overview highlighting some of the important aspects of C. auris epidemiology, pathogenesis and its puzzling global emergence.

scholarly journals Antifungal drugs work together to treat germs causing fungal infections

2021 ◽  
Author(s):  
Michael A Pfaller ◽  
Shawn A Messer ◽  
Lalitagauri M Deshpande ◽  
Paul R Rhomberg ◽  
Eric A Utt ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Genetic Differences ◽  
Antifungal Drugs ◽  
Hospital Environment ◽  
Plain Language ◽  
Candida Auris ◽  
Life Threatening ◽  
Almost All

Life-threatening infections can be caused by a fungus called Candida auris (shortened to C. auris) that is found in the hospital environment. This study looked at how well different drugs could treat C. auris infection. Samples were collected from 36 people who had C. auris infection. The samples were treated with single drugs and in combination. We found that the main drug types did not work on most samples. Genetic differences we found in the C. auris samples could explain why the main drugs did not work. However, a drug called isavuconazole worked on almost all samples. We also found that a drug called anidulafungin worked better against C. auris when it was combined with either isavuconazole or another drug called voriconazole. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF.

Susceptibility of Candida auris and Candida albicans to 21 germicides used in healthcare facilities

2019 ◽  
Vol 40 (3) ◽  
pp. 380-382 ◽  
Author(s):  
William A. Rutala ◽  
Hajime Kanamori ◽  
Maria F. Gergen ◽  
Emily E. Sickbert-Bennett ◽  
David J. Weber
Keyword(s):  
Fungal Pathogen ◽  
Infection Prevention ◽  
Antifungal Drugs ◽  
Prevention Strategies ◽  
Candida Auris ◽  
Healthcare Facilities ◽  
Surface Disinfection ◽  
Environmental Surfaces ◽  
Severe Infections ◽  
High Level

Candida auris is an emerging fungal pathogen that is often resistant to major classes of antifungal drugs. It is considered a serious global health threat because it can cause severe infections with frequent mortality in more than a dozen countries. It can survive on healthcare environmental surfaces for at least 7 days and can cause outbreaks in healthcare facilities. Clearly, infection prevention strategies, such as surface disinfection, will be essential to controlling Candida transmission. Unfortunately, data on the activity of antiseptics and disinfectants used in healthcare to inactivate this pathogen are limited.1–5 In this study, we investigated 12 different disinfectants (ie, 8 low- and intermediate-level disinfectants in 2 dilutions of sodium hypochlorite and 5 high-level disinfectants/chemical sterilants) and 9 antiseptics commonly used in healthcare facilities for their antimicrobial activity against C. auris and C. albicans.

scholarly journals Adenylyl Cyclase and Protein Kinase A Play Redundant and Distinct Roles in Growth, Differentiation, Antifungal Drug Resistance, and Pathogenicity of Candida auris

mBio ◽  
2021 ◽  
Author(s):  
Ji-Seok Kim ◽  
Kyung-Tae Lee ◽  
Myung Ha Lee ◽  
Eunji Cheong ◽  
Yong-Sun Bahn
Keyword(s):  
Drug Resistance ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Fungal Pathogen ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Candida Auris ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Kinase A

Despite the recently growing concern of pan-resistant Candida auris infection, the pathogenicity of this ascomycetous fungal pathogen and the signaling circuitries governing its resistance to antifungal drugs are largely unknown. Therefore, we analyzed the pathobiological functions of cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway in C. auris , which plays conserved roles in the growth and virulence of fungal pathogens.

scholarly journals Rampant transposition following RNAi loss causes hypermutation and antifungal drug resistance in clinical isolates of a human fungal pathogen

2021 ◽  
Author(s):  
Shelby Priest ◽  
Vikas Yadav ◽  
Cullen Roth ◽  
Tim Dahlmann ◽  
Ulrich Kueck ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Nonsense Mutation ◽  
Fungal Pathogen ◽  
Genetic Locus ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Gene Encoding ◽  
Antifungal Drug Resistance ◽  
Trait Locus ◽  
Almost All

Abstract Microorganisms survive and compete within their environmental niches and avoid evolutionary stagnation by stochastically acquiring mutations that enhance fitness. Although increased mutation rates are often deleterious in multicellular organisms, hypermutation can be beneficial for microbes in the context of strong selective pressures. To explore how hypermutation arises in nature and elucidate its consequences, we employed a collection of 387 sequenced clinical and environmental isolates of Cryptococcus neoformans. This fungal pathogen is responsible for ~ 15% of annual AIDS-related deaths and is associated with high mortality rates, attributable to a dearth of antifungal drugs and increasing drug resistance. Isolates were screened for the ability to rapidly acquire antifungal drug resistance, and two robust hypermutators were identified. Insertion of the non-LTR Cnl1 retrotransposon was found to be responsible for the majority of drug-resistant isolates. Long-read whole-genome sequencing revealed both hypermutator genomes have two unique features: 1) hundreds of Cnl1 copies organized in subtelomeric arrays on both ends of almost all chromosomes, and 2) a nonsense mutation in the first exon of ZNF3, a gene encoding an RNAi component involved in silencing transposons. Quantitative trait locus mapping identified a significant genetic locus associated with hypermutation that includes the mutant znf3 allele, and CRISPR-mediated genome editing of the znf3 single-base pair nonsense mutation abolished the hypermutation phenotype and restored siRNA production. In sum, hypermutation and drug resistance in these isolates results from loss of RNAi combined with subsequent accumulation of a large genomic burden of a novel transposable element in C. neoformans.

scholarly journals The Two-Component Response Regulator Ssk1 and the Mitogen-Activated Protein Kinase Hog1 Control Antifungal Drug Resistance and Cell Wall Architecture of Candida auris

mSphere ◽  
2020 ◽  
Vol 5 (5) ◽  
Author(s):  
Raju Shivarathri ◽  
Sabrina Jenull ◽  
Anton Stoiber ◽  
Manju Chauhan ◽  
Rounik Mazumdar ◽  
...  
Keyword(s):  
Cell Wall ◽  
Multidrug Resistance ◽  
Response Regulator ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Candida Auris ◽  
Content Type ◽  
Antifungal Drug Resistance ◽  
Two Component

ABSTRACT Candida auris is an emerging multidrug-resistant human fungal pathogen refractory to treatment by several classes of antifungal drugs. Unlike other Candida species, C. auris can adhere to human skin for prolonged periods of time, allowing for efficient skin-to-skin transmission in the hospital environments. However, molecular mechanisms underlying pronounced multidrug resistance and adhesion traits are poorly understood. Two-component signal transduction and mitogen-activated protein (MAP) kinase signaling are important regulators of adherence, antifungal drug resistance, and virulence. Here, we report that genetic removal of SSK1 encoding a response regulator and the mitogen-associated protein kinase HOG1 restores the susceptibility to both amphotericin B (AMB) and caspofungin (CAS) in C. auris clinical strains. The loss of SSK1 and HOG1 alters membrane lipid permeability, cell wall mannan content, and hyperresistance to cell wall-perturbing agents. Interestingly, our data reveal variable functions of SSK1 and HOG1 in different C. auris clinical isolates, suggesting a pronounced genetic plasticity affecting cell wall function, stress adaptation, and multidrug resistance. Taken together, our data suggest that targeting two-component signal transduction systems could be suitable for restoring C. auris susceptibility to antifungal drugs. IMPORTANCE Candida auris is an emerging multidrug-resistant (MDR) fungal pathogen that presents a serious global threat to human health. The Centers for Disease Control and Prevention (CDC) have classified C. auris as an urgent threat to public health for the next decade due to its major clinical and economic impact and the lack of effective antifungal drugs and because of future projections concerning new C. auris infections. Importantly, the Global Antimicrobial Resistance Surveillance System (GLASS) has highlighted the need for more robust and efficacious global surveillance schemes enabling the identification and monitoring of antifungal resistance in Candida infections. Despite the clinical relevance of C. auris infections, our overall understanding of its pathophysiology and virulence, its response to human immune surveillance, and the molecular basis of multiple antifungal resistance remains in its infancy. Here, we show a marked phenotypic plasticity of C. auris clinical isolates. Further, we demonstrate critical roles of stress response mechanisms in regulating multidrug resistance and show that cell wall architecture and composition are key elements that determine antifungal drug susceptibilities. Our data promise new therapeutic options to treat drug-refractory C. auris infections.

scholarly journals Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities

2021 ◽  
Vol 9 (4) ◽  
pp. 807
Author(s):  
Suhail Ahmad ◽  
Wadha Alfouzan
Keyword(s):  
Infection Control ◽  
Close Contact ◽  
Antifungal Susceptibility ◽  
Multidrug Resistant ◽  
Lessons Learned ◽  
Antifungal Drugs ◽  
Control Measures ◽  
Candida Auris ◽  
Healthcare Facilities ◽  
Infection Control Measures

Candida auris, a recently recognized, often multidrug-resistant yeast, has become a significant fungal pathogen due to its ability to cause invasive infections and outbreaks in healthcare facilities which have been difficult to control and treat. The extraordinary abilities of C. auris to easily contaminate the environment around colonized patients and persist for long periods have recently resulted in major outbreaks in many countries. C. auris resists elimination by robust cleaning and other decontamination procedures, likely due to the formation of ‘dry’ biofilms. Susceptible hospitalized patients, particularly those with multiple comorbidities in intensive care settings, acquire C. auris rather easily from close contact with C. auris-infected patients, their environment, or the equipment used on colonized patients, often with fatal consequences. This review highlights the lessons learned from recent studies on the epidemiology, diagnosis, pathogenesis, susceptibility, and molecular basis of resistance to antifungal drugs and infection control measures to combat the spread of C. auris infections in healthcare facilities. Particular emphasis is given to interventions aiming to prevent new infections in healthcare facilities, including the screening of susceptible patients for colonization; the cleaning and decontamination of the environment, equipment, and colonized patients; and successful approaches to identify and treat infected patients, particularly during outbreaks.

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