Echinocandins as Biotechnological Tools for Treating Candida auris Infections

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.

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Persisting intrahospital transmission of multidrug-resistant Klebsiella pneumoniae and challenges for infection control

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2019.153 ◽

2019 ◽

Vol 40 (8) ◽

pp. 904-909 ◽

Cited By ~ 1

Author(s):

Isabelle Vock ◽

Sarah Tschudin-Sutter

Keyword(s):

Klebsiella Pneumoniae ◽

Infection Control ◽

Multidrug Resistant ◽

Global Scale ◽

Resistance Mechanisms ◽

Healthcare Associated Infections ◽

The Past ◽

Healthcare Settings ◽

Healthcare Associated ◽

Antibiotic Agents

AbstractIn the past several decades, the incidence of Klebsiella pneumoniae harboring resistance mechanisms against multiple antibiotic agents has increased on a global scale. We discuss reasons for ongoing transmission of multidrug-resistant K. pneumoniae in healthcare settings, which has resulted in the successful spread and establishment of this pathogen. It is now one of the most important causes of healthcare-associated infections worldwide.

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Compulsory External Standardised Education for Decontamination Sciences: Going in the Right Direction or a Step Too Far?

Journal of Perioperative Practice ◽

10.1177/175045891602201203 ◽

2012 ◽

Vol 22 (12) ◽

pp. 383-388

Author(s):

Angela Cobbold ◽

Sue Lord

Keyword(s):

The United States ◽

Medical Procedures ◽

Healthcare Associated Infections ◽

Cross Contamination ◽

Patient Contact ◽

The Past ◽

Jakob Disease ◽

The Right ◽

Healthcare Associated ◽

Surgical Operations

In the United States, approximately 46.5 million surgical and medical procedures, including approximately 5 million gastrointestinal endoscopies are performed annually (Rutala & Weber 2008). In contrast, there are some 4.2 million surgical operations carried out annually in England (RCS 2012). The majority of these procedures involve patient contact with reusable invasive medical devices (RIMDs). Over the past 15 years, there have been significant changes in guidance and legislation relating to decontamination processes, mainly resulting from the focus on variant Creutzfeldt-Jakob disease (vCJD) (NSH 2001, DH 2003) and the need to tackle increasing problems with healthcare associated infections (HCAIs). Therefore, with approximately 350 NHS hospitals in England alone (RCS 2012), there is potential for a major risk of cross contamination for patients and staff.

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Is Candida auris here to stay? An interview with Dimitrios Kontoyiannis

Future Microbiology ◽

10.2217/fmb-2019-0210 ◽

2019 ◽

Vol 14 (13) ◽

pp. 1083-1085

Author(s):

Dimitrios P Kontoyiannis

Keyword(s):

Fungal Pathogen ◽

Immunocompromised Host ◽

Cancer Center ◽

Candida Auris ◽

Past President ◽

H Index ◽

The Past ◽

The Usa ◽

President Elect ◽

Md Anderson

In this exclusive interview, Dimitrios P Kontoyiannis discusses current mycology hot topic, Candida auris. With a focus on the current knowns and unknowns for the pathogenesis, resistance and transmission of this emerging fungal pathogen, in addition to a look at therapeutics and future perspectives. This interview was conducted by Ellen Colvin, Commissioning Editor of Future Microbiology. Dimitrios P Kontoyiannis is the Texas 4000 distinguished endowed professor and deputy head in the Division of Internal Medicine at MD Anderson Cancer Center in Houston (TX, USA). Dr Kontoyiannis has authored over 550 peer-reviewed manuscripts and has given over 330 lectures in national and international conferences and academic institutions in the USA and abroad. He is considered a leading mycology expert world-wide with an H index of 101 and over 43,000 citations. His research group is credited for many and sustained contributions to clinical, translational and experimental mycology. He is the recipient of many national and international awards and is the past president elect of Immunocompromised Host Society (2016–2018).

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Candida auris: a fungus with identity crisis

Pathogens and Disease ◽

10.1093/femspd/ftaa034 ◽

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.

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

mSphere ◽

10.1128/msphere.00458-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 24

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

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2019.1 ◽

2019 ◽

Vol 40 (3) ◽

pp. 380-382 ◽

Cited By ~ 18

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.

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Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal PathogenCandida auris

mSphere ◽

10.1128/msphere.00506-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 18

Author(s):

Alison M. Day ◽

Megan M. McNiff ◽

Alessandra da Silva Dantas ◽

Neil A. R. Gow ◽

Janet Quinn

Keyword(s):

Protein Kinase ◽

Stress Resistance ◽

Fungal Pathogen ◽

Antifungal Drugs ◽

Control Measures ◽

Emerging Pathogen ◽

Candida Auris ◽

Content Type ◽

Resistance Profile

ABSTRACTCandida aurishas recently emerged as an important, multidrug-resistant fungal pathogen of humans. Comparative studies indicate that despite high levels of genetic divergence,C. aurisis as virulent as the most pathogenic member of the genus,Candida albicans. However, key virulence attributes ofC. albicans, such as morphogenetic switching, are not utilized byC. auris, indicating that this emerging pathogen employs alternative strategies to infect and colonize the host. An important trait required for the pathogenicity of many fungal pathogens is the ability to adapt to host-imposed stresses encountered during infection. Here, we investigated the relative resistance ofC. aurisand other pathogenicCandidaspecies to physiologically relevant stresses and explored the role of the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK) in promoting stress resistance and virulence. In comparison toC. albicans,C. aurisis relatively resistant to hydrogen peroxide, cationic stress, and cell-wall-damaging agents. However, in contrast to otherCandidaspecies examined,C. auris was unable to grow in an anaerobic environment and was acutely sensitive to organic oxidative-stress-inducing agents. An analysis ofC. aurishog1Δ cells revealed multiple roles for this SAPK in stress resistance, cell morphology, aggregation, and virulence. These data demonstrate thatC. aurishas a unique stress resistance profile compared to those of other pathogenicCandidaspecies and that the Hog1 SAPK has pleiotropic roles that promote the virulence of this emerging pathogen.IMPORTANCEThe rapid global emergence and resistance ofCandidaauristo current antifungal drugs highlight the importance of understanding the virulence traits exploited by this human fungal pathogen to cause disease. Here, we characterize the stress resistance profile ofC. aurisand the role of the Hog1 stress-activated protein kinase (SAPK) in stress resistance and virulence. Our findings thatC. aurisis acutely sensitive to certain stresses may facilitate control measures to prevent persistent colonization in hospital settings. Furthermore, our observation that the Hog1 SAPK promotesC. aurisvirulence akin to that reported for many other pathogenic fungi indicates that antifungals targeting Hog1 signaling would be broad acting and effective, even on emerging drug-resistant pathogens.

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Prevalence, epidemiology and clinical outcome of Candida auris infections: Experience from a tertiary care hospital in Jaipur

Tropical Doctor ◽

10.1177/00494755211028685 ◽

2021 ◽

pp. 004947552110286

Author(s):

Daisy Bacchani ◽

Ekadashi Rajni ◽

Vishnu K Garg ◽

Richa Sharma ◽

Ved P Mamoria

Keyword(s):

Tertiary Care Hospital ◽

Tertiary Care ◽

Multidrug Resistant ◽

Care Hospital ◽

Emerging Pathogen ◽

Broad Spectrum Antibiotic ◽

Candida Auris ◽

History Of ◽

Echinocandin Resistance ◽

Healthcare Associated

Candida auris is identified as an emerging pathogen worldwide. It is multidrug resistant and causes invasive healthcare-associated infections. Our retrospective study was conducted to determine the prevalence and epidemiology of C. auris infections in a tertiary care hospital in Jaipur. 24 clinical C. auris strains were included, most being from urine. The majority patients needed intensive care and had at least one underlying co-morbid condition. A history of broad-spectrum antibiotic or antifungal usage was present in 85%. Fluconazole, voriconazole, amphotericin B and 5-fluorocytosine resistance was seen in 96, 42, 33 and 8% isolates respectively. No echinocandin resistance was noted.

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

mBio ◽

10.1128/mbio.02729-21 ◽

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.

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