Antifungal Resistance Trends of Candida auris Clinical Isolates in New York and New Jersey from 2016 to 2020

Kilburn, Shannon; Innes, Gabriel K.; Quinn, Monica; Southwick, K; Ostrowsky, Belinda; Greenko, Jane; Lutterloh, Emily; Greeley, Rebecca; Magleby, Reed; Chaturvedi, Sudha; Chaturvedi, Sudha

doi:10.1128/aac.02242-21

Cited by 38 publications

(33 citation statements)

References 12 publications

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“…C. auris are highly drug-resistant pathogenic fungi that have rapidly spread across the globe since their identification in 2009. More than 99% of the C. auris isolates in the United States are resistant to fluconazole, 50-60% are resistant to amphotericin B, and less than 10% are resistant to echinocandins [39][40][41] . Thus, echinocandin drugs are the first-line empiric therapy for C. auris infections, as recommended by the CDC 42 .…”

Section: Discussionmentioning

confidence: 99%

Echinocandin heteroresistance causes prophylaxis failure and facilitates breakthroughCandida parapsilosisinfection

Zhai

Liao

Jaggavarapu

et al. 2022

Preprint

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Antimicrobial drug resistance is a major problem in the prevention and treatment of infectious diseases. For patients on antimicrobial prophylaxis during cancer treatment and organ transplantation, breakthrough infections represent a significant and often unexplained cause of morbidity. Here, in high-risk patients on micafungin prophylaxis, we reveal that heteroresistance, the presence of a phenotypically unstable, low frequency subpopulation of resistant cells (~1 in 10,000), causes breakthrough bloodstream infections by Candida parapsilosis strains that were misclassified as susceptible by standard antimicrobial susceptibility testing. Genome-matched micafungin heteroresistant strains were isolated from the intestinal reservoir prior to invasive disease. To identify heteroresistance, we harnessed whole genome sequence analysis of 118 clinical C. parapsilosis strains and extracted six genetic features into a predictive machine learning model that distinguished heteroresistant strains with high accuracy. These data directly implicate heteroresistance in unexplained prophylaxis failure and highlight a proof-of-principle approach to detect this phenomenon and inform clinical decisions.

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Section: Discussionmentioning

confidence: 99%

Echinocandin heteroresistance causes prophylaxis failure and facilitates breakthroughCandida parapsilosisinfection

Zhai

Liao

Jaggavarapu

et al. 2022

Preprint

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“…This indicates that sphingolipids play an important role in the ability of C. auris to handle amphotericin B. Together with the different sphingolipid composition (22)(23)(24), this could explain why some many clinical isolates of C. auris show a high tolerance to amphotericin B which is not common for C. albicans or C. glabrata (13,14,28). The antifungal activity of amphotericin B depends on the balance of different interactions with ergosterol, sphingolipids and phospholipids.…”

Section: Discussionmentioning

confidence: 99%

The sphingolipid inhibitor myriocin increases susceptibility of Candida auris to amphotericin B

Stieber

Junghanns

Wilhelm

et al. 2022

Preprint

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The emerging human fungal pathogen Candida auris can cause of hospital outbreaks by transmission between patients and / or medical care staff. It is known for a fast adaption to environmental stress and antifungal treatment. Besides resistance to fluconazole in most isolates, C. auris frequently shows limited susceptibility to echinocandins and even to amphotericin B. Therefore, multidrug resistance (MDR) is frequently found in clinical isolates, leading to a need for new therapeutic targets and compounds. One of those targets could be sphingolipids which are an integral part of the cell membrane and are important for membrane fluidity and the formation of lipid rafts. Here, we show that myriocin-mediated inhibition of the de novo sphingolipid biosynthesis caused severe growth defects in C. auris. Sublethal myriocin concentrations increase fungal susceptibility to amphotericin B and anidulafungin. While the effect is limited for anidulafungin, even isolates that show phenotypic resistance to amphotericin B became susceptible in presence of myriocin. A large-scale screening of 59 clinical isolates validated these initial results and showed that inhibition of the de novo sphingolipid biosynthesis increases C. auris susceptibility to amphotericin B. These observations open new options for future therapeutic strategies and illustrate that sphingolipids might play a pivotal role for the ability of C. auris to develop resistance against amphotericin B.

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“…The majority of C. auris isolates are found to have in vitro susceptibility to echinocandins although resistance is well documented and varies by geographic region. 26 , 48 , 49 Clinicians must have a high degree of suspicion when patients fail to respond to an echinocandin and a low threshold to ensure susceptibility testing is undertaken.…”

Section: Methods Of Antifungal Resistance Testingmentioning

confidence: 99%

Clinical utility of antifungal susceptibility testing

McCarty

Luethy

Baddley

et al. 2022

JAC-Antimicrobial Resistance

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Invasive fungal diseases cause significant morbidity and mortality, in particular affecting immunocompromised patients. Resistant organisms are of increasing importance, yet there are many notable differences in the ability to both perform and interpret antifungal susceptibility testing compared with bacteria. In this review, we will highlight the strengths and limitations of resistance data of pathogenic yeasts and moulds that may be used to guide treatment and predict clinical outcomes.

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Antifungal Resistance Trends of Candida auris Clinical Isolates in New York and New Jersey from 2016 to 2020

Cited by 38 publications

References 12 publications

Echinocandin heteroresistance causes prophylaxis failure and facilitates breakthroughCandida parapsilosisinfection

Echinocandin heteroresistance causes prophylaxis failure and facilitates breakthroughCandida parapsilosisinfection

The sphingolipid inhibitor myriocin increases susceptibility of Candida auris to amphotericin B

Clinical utility of antifungal susceptibility testing

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