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

Kean, Ryan; Ramage, Gordon

doi:10.1128/msphere.00458-19

Cited by 105 publications

(129 citation statements)

References 73 publications

Supporting

Mentioning

115

Contrasting

Unclassified

Order By: Relevance

“…Candida auris can persist on different types of surfaces, including moist, dry, and plastic surfaces, with the potential of survival for up to 14 days [33][34][35][36][37]. The success of environmental decontamination was variable in the literature utilizing mostly materials and methods tested earlier against resistant Gram-positive and Gram-negative pathogens [17,21,38,39].…”

Section: Discussionmentioning

confidence: 99%

Ongoing Challenges with Healthcare-Associated Candida auris Outbreaks in Oman

Maani

Paul

Al-Rashdi

et al. 2019

JoF

View full text Add to dashboard Cite

Candida auris has emerged in the past decade as a multi-drug resistant public health threat causing health care outbreaks. Here we report epidemiological, clinical, and microbiological investigations of a C. auris outbreak in a regional Omani hospital between April 2018 and April 2019. The outbreak started in the intensive care areas (intensive care unit (ICU), coronary care unit (CCU), and high dependency unit) but cases were subsequently diagnosed in other medical and surgical units. In addition to the patients' clinical and screening samples, environmental swabs from high touch areas and from the hands of 35 staff were collected. All the positive samples from patients and environmental screening were confirmed using MALDI-TOF, and additional ITS-rDNA sequencing was done for ten clinical and two environmental isolates. There were 32 patients positive for C. auris of which 14 (43.8%) had urinary tract infection, 11 (34.4%) had candidemia, and 7 (21.8%) had asymptomatic skin colonization. The median age was 64 years (14-88) with 17 (53.1%) male and 15 (46.9%) female patients. Prior to diagnosis, 21 (65.6%) had been admitted to the intensive care unit, and 11 (34.4%) had been nursed in medical or surgical wards. The crude mortality rate in our patient's cohort was 53.1. Two swabs collected from a ventilator in two different beds in the ICU were positive for C. auris. None of the health care worker samples were positive. Molecular typing showed that clinical and environmental isolates were genetically similar and all belonged to the South Asian C. auris clade I. Most isolates had non-susceptible fluconazole (100%) and amphotericin B (33%)

show abstract

Section: Discussionmentioning

confidence: 99%

Ongoing Challenges with Healthcare-Associated Candida auris Outbreaks in Oman

Maani

Paul

Al-Rashdi

et al. 2019

JoF

View full text Add to dashboard Cite

show abstract

“…C. auris is an emerging multidrug resistant fungal pathogen that is known to cause nosocomial infections with ‘superbug”-like traits (18). C. auris was first discovered in 2009 in Southeast Asia and now it is present in 33 countries across 6 continents.…”

Section: Resultsmentioning

confidence: 99%

“…(data not included). Candida auris is an emerging and multi antifungal resistant strain that causes nosocomial infection and has been reported recently across the world (18). Our bioscreen-based growth curve monitoring assay with 1 showed better activity than clinical antifungal drug FLU (Fig.…”

Section: Discussionmentioning

confidence: 99%

Broad-Spectrum Antifungal Activities and Mechanism of Drimane Sesquiterpenoids

Edouarzin

Horn

Paduyal

et al. 2019

Preprint

View full text Add to dashboard Cite

25Eight drimane sesquiterpenoids including (-)-drimenol and (+)-albicanol were synthesized 26 from (+)-sclareolide and evaluated for their antifungal activities. Three compounds, (-)-drimenol, 27 (+)-albicanol, and (1R,2R,4aS,8aS)-2-hydroxy-2,5,5,8a-tetramethyl-decahydronaphthalene-1-28 carbaldehyde (4) showed strong activity against C. albicans. (-)-Drimenol, the strongest inhibitor 29 of the three, (at concentrations of 8 -64 g/ml, causing 100% death of fungi), acts not only against 30 C. albicans as a fungicidal manner, but also inhibits other fungi such as Aspergillus, Cryptococcus, 31 Pneumocystis, Blastomyces, Fusarium, Rhizopus, Saksenaea and FLU resistant strains of C. 32 albicans, C. glabrata, C. krusei, C. parapsilosis and C. auris. These observations suggest drimenol 33 is a broad-spectrum antifungal agent. At high concentration (100 μg/ml), drimenol caused a 34 rupture of the fungal cell wall/membrane. In a nematode model of C. albicans infection, drimenol 35 rescued the worms from C. albicans-mediated death, indicating drimenol is tolerable and bioactive 36 in a metazoan. Genome-wide fitness profiling assays of both S. cerevisiae (nonessential 37 homozygous and essential heterozygous) and C. albicans (Tn-insertion mutants) collections 38 revealed putative genes and pathways affected by drimenol. Using a C. albicans mutants spot 39 assay, the Crk1 kinase associated gene products, Ret2, Cdc37, and novel putative targets 40 orf19.759, orf19.1672, and orf19.4382 were revealed to be the potential targets of drimenol. 41 Further, computational modeling results suggest possible modification of the structure of drimenol 42 including the A ring for improving antifungal activity. 43 44 45 46 47 48 Life-threatening fungal infections are an important cause of morbidity and mortality, 49 particularly for patients with immune deficiency and those who are undergoing chemotherapeutic 50 treatments. Some of the leading invasive fungal pathogens include Candida sp., Aspergillus sp. 51 and Cryptococcus sp. Currently, the antifungal therapeutic options are limited, especially when 52 compared to available antibacterial agents (1-4). Among the five classes of antifungals, azoles, 53 echiocandins, polyenes, allylamines, and pyrimidine derivatives, only three are used clinically; 54 azoles, echiocandins, and polyenes. Azole drugs, such as fluconazole (FLU), inhibit ergosterol 55 synthesis through inhibition of lanosterol 14--demethylase, impairing formation of the fungal 56 cell wall. Echocandins, such as caspofungin (CAS), block 1,3--glucan synthase and lead to 57 depletion of glucan in fungal cell wall. Polyenes, including amphotericin B (AMB), bind to 58 ergosterol in fungal cell membrane and change the cell membrane transition temperature, resulting 59 in leakage of ions and small organic molecules, and eventual cell death. Allylamines, such as 60 amorolfin, affect ergosterol synthesis by inhibition of squalene epoxidase. Pyrimidines, such as 61 flucytosine (or 5-fluorocytosine), block nucleic acid synthesis,...

show abstract

“…Этот грибок является причиной нозокомиальных инфекций, при которых уровень летальности достигает 72% [10][11][12]. Такой устрашающий прогноз инфекции C. auris связан с тем, что грибок обладает множественной лекарственной устойчивостью, которая характеризуется резистентностью к трем и более группам антимикотических препаратов [10,13,14]. Особую проблему составляют устойчивость C. auris к факторам внешней среды и сложность обнаружения при диагностических исследованиях.…”

Section: Introductionunclassified

<i>Candida auris</i>: Problems in Diagnostics and Management

Иванов¹,

Куличенко

2020

Vopr. sovr. pediatr.

View full text Add to dashboard Cite

1 Морозовская городская детская клиническая больница, Москва, Российская Федерация 2 Российский национальный исследовательский медицинский университет им. Н.И. Пирогова, Москва, Российская Федерация Грибковые инфекции в последнее время представляют все бо льшую опасность для длительно пребывающих в стационаре пациентов, которые получают иммуносупрессивную терапию и страдают иммунодефицитными состояниями. Обзор литературы посвящен Candida auris, впервые выделенной в 2009 г. В дальнейшем стало известно, что этот грибок является причиной нозокомиальных инфекций, летальность при которых достигает 72%. C. auris обладает множественной лекарственной устойчивостью, способна длительно существовать в окружающей среде. Основную проблему в клинической практике представляет недостаточная чувствительность существующих диагностических тестов для обнаружения этого грибка, что приводит к неверному подбору терапии и увеличивает риск фатального исхода инфекции. В последнем отчете Центра по контролю заболеваний (США) C. auris выделена в группу инфекционных агентов, представляющих наибольшую опасность для общественного здравоохранения. Ключевые слова: Candida auris, грибковая инфекция, лекарственная устойчивость, мультирезистентность, мультирезистентный микроорганизм, противогрибковые препараты, профилактика инфекций, эпидемиология. (Для цитирования: Иванов А. А., Куличенко Т. В. Candida auris: проблемы диагностики и лечения.Fungal infections in these days have the major risk for patients who receive immunosuppressive therapy and suffer from immunodeficiency conditions during their long stay in a hospital. The literature review is dedicated to Candida auris that was firstly isolated in 2009. Later it was reported that this fungus is the cause of nosocomial infections which mortality rate reaches 72%. C. auris has multi-drug resistance and it can survive for a long time in the environment. The lack of sensitivity of diagnostic tests for this fungus detection is the main problem in clinical practice. This leads to inappropriate management and increases the risk of mortality due to infection. C. auris was included in the group of infectious agents that has the highest danger to public health according to the recent report of the Centre for Disease Control (USA).

show abstract

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

Cited by 105 publications

References 73 publications

Ongoing Challenges with Healthcare-Associated Candida auris Outbreaks in Oman

Ongoing Challenges with Healthcare-Associated Candida auris Outbreaks in Oman

Broad-Spectrum Antifungal Activities and Mechanism of Drimane Sesquiterpenoids

<i>Candida auris</i>: Problems in Diagnostics and Management

Contact Info

Product

Resources

About