Surveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates

Talbot, Jessica J.; Subedi, Shradha; Halliday, Catriona; Hibbs, David E.; Lai, Felcia; Lopez‐Ruiz, Francisco J.; Harper, Lincoln A.; Park, Robert; Cuddy, William S.; Biswas, Chayanika; Cooley, Louise; Carter, Dee; Sorrell, Tania C.; Barrs, Vanessa R.; Chen, Sharon C.-A.

doi:10.1093/jac/dky187

Cited by 31 publications

(32 citation statements)

References 23 publications

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“…While time efficient, these commercial assays are limited by the fact that CYP51A is a single copy gene, and that they detect only azole resistance involving the tandem repeat. In Australia where the incidence of azole resistance is low (< 3%), 2/3 azole resistant isolates had the G54R mutation associated with high MICs to itraconazole and posaconazole (Talbot et al, 2018). A recent study from the United Kingdom employing the AsperGenius assay R (PathoNostics BV) showed that 16/22 (73%) isolates with the resistant phenotype harbored no mutations detected by this test (Abdolrasouli et al, 2018).…”

Section: Molecular Methods To Detect Azole Resistance In Aspergillus mentioning

confidence: 99%

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

et al. 2020

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Section: Molecular Methods To Detect Azole Resistance In Aspergillus mentioning

confidence: 99%

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

et al. 2020

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“…Countries reporting the presence of azole-resistant Aspergillus fumigatus and mechanisms of resistance in surveyed isolates [47,48,49,52,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97]. …”

Section: Figurementioning

confidence: 99%

Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens

Friedman

Schwartz

2019

JoF

276

200

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: The landscape of clinical mycology is constantly changing. New therapies for malignant and autoimmune diseases have led to new risk factors for unusual mycoses. Invasive candidiasis is increasingly caused by non-albicans Candida spp., including C. auris, a multidrug-resistant yeast with the potential for nosocomial transmission that has rapidly spread globally. The use of mould-active antifungal prophylaxis in patients with cancer or transplantation has decreased the incidence of invasive fungal disease, but shifted the balance of mould disease in these patients to those from non-fumigatus Aspergillus species, Mucorales, and Scedosporium/Lomentospora spp. The agricultural application of triazole pesticides has driven an emergence of azole-resistant A. fumigatus in environmental and clinical isolates. The widespread use of topical antifungals with corticosteroids in India has resulted in Trichophyton mentagrophytes causing recalcitrant dermatophytosis. New dimorphic fungal pathogens have emerged, including Emergomyces, which cause disseminated mycoses globally, primarily in HIV infected patients, and Blastomyces helicus and B. percursus, causes of atypical blastomycosis in western parts of North America and in Africa, respectively. In North America, regions of geographic risk for coccidioidomycosis, histoplasmosis, and blastomycosis have expanded, possibly related to climate change. In Brazil, zoonotic sporotrichosis caused by Sporothrix brasiliensis has emerged as an important disease of felines and people.

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“…In addition, given the limited availability of antifungal drugs to treat fungal infections, this increase in resistance rates found in clinical practice poses a substantial problem and could result in treatment failure and a consequent increase in mortality rates [99]. Current local azole resistance rates vary between 0 and 26%, variation occurring according to geographic region and patient population [86,91,97,[100][101][102][103][104][105][106]. An investigation, involving 13 countries in four continents, found an azole resistance rate of 6% among 2026 Aspergillus isolates evaluated [107].…”

Section: Aspergillus Azole Resistancementioning

confidence: 99%

“…Point mutations as G54 and M220 can change the protein structure, which affects the docking of certain azole compounds for the whole protein [114][115][116]. On the other hand, mutations such as TR 34 /L98H, which confers pan-azole resistance [100,101], and TR 46 /Y121F/T289A, apparently more related to a high level of voriconazole resistance and variable susceptibility to itraconazole [114,117,118], are reported in environmental strains [101,119], in patients with long-term treatment as well as in patients with IA [90,106,120,121].…”

Section: Main Mechanisms Of Azole Resistancementioning

confidence: 99%

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance

et al. 2020

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The One Health context considers health based on three pillars: humans, animals, and environment. This approach is a strong ally in the surveillance of infectious diseases and in the development of prevention strategies. Aspergillus spp. are fungi that fit substantially in this context, in view of their ubiquity, as well as their importance as plant pathogens, and potentially fatal pathogens for, particularly, humans and avian species. In addition, the emergence of azole resistance, mainly in Aspergillus fumigatus sensu stricto, and the proven role of fungicides widely used on crops, reinforces the need for a multidisciplinary approach to this problem. Avian species are involved in short and long distance travel between different types of landscapes, such as agricultural fields, natural environments and urban environments. Thus, birds can play an important role in the dispersion of Aspergillus, and of special concern, azole-resistant strains. In addition, some bird species are particularly susceptible to aspergillosis. Therefore, avian aspergillosis could be considered as an environmental health indicator. In this review, aspergillosis in humans and birds will be discussed, with focus on the presence of Aspergillus in the environment. We will relate these issues with the emergence of azole resistance on Aspergillus. These topics will be therefore considered and reviewed from the “One Health” perspective.

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Surveillance for azole resistance in clinical and environmental isolates of Aspergillus fumigatus in Australia and cyp51A homology modelling of azole-resistant isolates

Abstract: Azole resistance is uncommon in Australian clinical and environmental A. fumigatus isolates; further surveillance is indicated.

Cited by 31 publications

References 23 publications

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

A New Age in Molecular Diagnostics for Invasive Fungal Disease: Are We Ready?

Emerging Fungal Infections: New Patients, New Patterns, and New Pathogens

Aspergillosis, Avian Species and the One Health Perspective: The Possible Importance of Birds in Azole Resistance

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