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 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 A marine microbiome antifungal targets urgent-threat drug-resistant fungi

Science ◽  
2020 ◽  
Vol 370 (6519) ◽  
pp. 974-978 ◽  
Author(s):  
Fan Zhang ◽  
Miao Zhao ◽  
Doug R. Braun ◽  
Spencer S. Ericksen ◽  
Jeff S. Piotrowski ◽  
...  
Keyword(s):  
Mode Of Action ◽  
Fungal Pathogens ◽  
Antifungal Drugs ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Candida Auris ◽  
Marine Animals ◽  
Multiple Drug Resistant

New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug–resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as C. auris.

scholarly journals Echinocandins as Biotechnological Tools for Treating Candida auris Infections

2020 ◽  
Vol 6 (3) ◽  
pp. 185
Author(s):  
Elizabete de Souza Cândido ◽  
Flávia Affonseca ◽  
Marlon Henrique Cardoso ◽  
Octavio Luiz Franco
Keyword(s):  
Fungal Pathogen ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Healthcare Associated Infections ◽  
Candida Auris ◽  
High Interest ◽  
The Past ◽  
Recent Emergence ◽  
Echinocandin Resistance ◽  
Healthcare Associated

Candida auris has been reported in the past few years as an invasive fungal pathogen of high interest. Its recent emergence in healthcare-associated infections triggered the efforts of researchers worldwide, seeking additional alternatives to the use of traditional antifungals such as azoles. Lipopeptides, specially the echinocandins, have been reported as an effective approach to control pathogenic fungi. However, despite its efficiency against C. auris, some isolates presented echinocandin resistance. Thus, therapies focused on echinocandins’ synergism with other antifungal drugs were widely explored, representing a novel possibility for the treatment of C. auris infections.

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.

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 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.

scholarly journals Potent Synergistic Interactions between Lopinavir and Azole Antifungal Drugs against Emerging Multidrug-Resistant Candida auris

2020 ◽  
Vol 65 (1) ◽  
pp. e00684-20 ◽  
Author(s):  
Hassan E. Eldesouky ◽  
Ehab A. Salama ◽  
Nadia A. Lanman ◽  
Tony R. Hazbun ◽  
Mohamed N. Seleem
Keyword(s):  
Nile Red ◽  
Atp Synthesis ◽  
Multidrug Resistant ◽  
Antifungal Drugs ◽  
Hiv Protease ◽  
Candida Auris ◽  
Content Type ◽  
Azole Antifungals ◽  
Synergistic Interactions ◽  
Recent Emergence

ABSTRACTThe limited therapeutic options and the recent emergence of multidrug-resistant Candida species present a significant challenge to human medicine and underscore the need for novel therapeutic approaches. Drug repurposing appears as a promising tool to augment the activity of current azole antifungals, especially against multidrug-resistant Candida auris. In this study, we evaluated the fluconazole chemosensitization activities of 1,547 FDA-approved drugs and clinical molecules against azole-resistant C. auris. This led to the discovery that lopinavir, an HIV protease inhibitor, is a potent agent capable of sensitizing C. auris to the effect of azole antifungals. At a therapeutically achievable concentration, lopinavir exhibited potent synergistic interactions with azole drugs, particularly with itraconazole against C. auris (fractional inhibitory concentration index [ΣFICI] ranged from 0.04 to 0.09). Additionally, the lopinavir/itraconazole combination enhanced the survival rate of C. auris-infected Caenorhabditis elegans by 90% and reduced the fungal burden in infected nematodes by 88.5% (P < 0.05) relative to that of the untreated control. Furthermore, lopinavir enhanced the antifungal activity of itraconazole against other medically important Candida species, including C. albicans, C. tropicalis, C. krusei, and C. parapsilosis. Comparative transcriptomic profiling and mechanistic studies revealed that lopinavir was able to significantly interfere with the glucose permeation and ATP synthesis. This compromised the efflux ability of C. auris and consequently enhanced the susceptibility to azole drugs, as demonstrated by Nile red efflux assays. Altogether, these findings present lopinavir as a novel, potent, and broad-spectrum azole-chemosensitizing agent that warrants further investigation against recalcitrant Candida infections.

scholarly journals The Quiet and Underappreciated Rise of Drug-Resistant Invasive Fungal Pathogens

2020 ◽  
Vol 6 (3) ◽  
pp. 138 ◽  
Author(s):  
Amir Arastehfar ◽  
Cornelia Lass-Flörl ◽  
Rocio Garcia-Rubio ◽  
Farnaz Daneshnia ◽  
Macit Ilkit ◽  
...  
Keyword(s):  
Fungal Pathogens ◽  
Molecular Mechanisms ◽  
Fungal Infections ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Candida Auris ◽  
Recent Emergence ◽  
Invasive Infections

Human fungal pathogens are attributable to a significant economic burden and mortality worldwide. Antifungal treatments, although limited in number, play a pivotal role in decreasing mortality and morbidities posed by invasive fungal infections (IFIs). However, the recent emergence of multidrug-resistant Candida auris and Candida glabrata and acquiring invasive infections due to azole-resistant C. parapsilosis, C. tropicalis, and Aspergillus spp. in azole-naïve patients pose a serious health threat considering the limited number of systemic antifungals available to treat IFIs. Although advancing for major fungal pathogens, the understanding of fungal attributes contributing to antifungal resistance is just emerging for several clinically important MDR fungal pathogens. Further complicating the matter are the distinct differences in antifungal resistance mechanisms among various fungal species in which one or more mechanisms may contribute to the resistance phenotype. In this review, we attempt to summarize the burden of antifungal resistance for selected non-albicansCandida and clinically important Aspergillus species together with their phylogenetic placement on the tree of life. Moreover, we highlight the different molecular mechanisms between antifungal tolerance and resistance, and comprehensively discuss the molecular mechanisms of antifungal resistance in a species level.

The Chemistry of Drugs to Treat Candida albicans

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea
Keyword(s):  
Candida Species ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Drug Classes ◽  
Life Threatening ◽  
Antifungal Substances ◽  
High Level ◽  
Systemic Infections ◽  
New Compounds ◽  
Level Resistance

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.

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