Azole resistance in <i>Aspergillus</i> species: promising therapeutic options

Pasula, Shirisha; Chandrasekar, Pranatharthi H.

doi:10.1080/14656566.2021.1940134

Cited by 6 publications

(3 citation statements)

References 63 publications

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“…1 ) [ 24 ]. Due to variability in agricultural use of azole-containing pesticides, scarce routine surveillance programs, and limited availability of routine susceptibility testing, there is a lack of relevant, detailed epidemiological data [ 25 ]. This could explain, in part, the enormous variability of ARAF prevalence in different countries [ 26 ].…”

Section: Epidemiology Of Azole-resistant a Fumigatusmentioning

confidence: 99%

“…These tests are easier to perform and comparable to the EUCAST/CLSI microdilution standard, but they also need a positive culture. [1,26] Genotypic testing for azole resistance is based mostly on PCR methods, targeting directly the most frequent point mutations in the cyp51A gene and its promoter and the tandem repeat insertions [1,25,108]. Currently, there are three different commercial kits used in Europe for the genotypic detection of azole resistance [109].…”

Section: Diagnosis Of Azole-resistancementioning

confidence: 99%

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Invasive Aspergillosis and the Impact of Azole-resistance

Bosetti

Neofytos

2023

Curr Fungal Infect Rep

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Purpose of Review IA (invasive aspergillosis) caused by azole-resistant strains has been associated with higher clinical burden and mortality rates. We review the current epidemiology, diagnostic, and therapeutic strategies of this clinical entity, with a special focus on patients with hematologic malignancies. Recent Findings There is an increase of azole resistance in Aspergillus spp. worldwide, probably due to environmental pressure and the increase of long-term azole prophylaxis and treatment in immunocompromised patients (e.g., in hematopoietic stem cell transplant recipients). The therapeutic approaches are challenging, due to multidrug-resistant strains, drug interactions, side effects, and patient-related conditions. Summary Rapid recognition of resistant Aspergillus spp. strains is fundamental to initiate an appropriate antifungal regimen, above all for allogeneic hematopoietic cell transplantation recipients. Clearly, more studies are needed in order to better understand the resistance mechanisms and optimize the diagnostic methods to identify Aspergillus spp. resistance to the existing antifungal agents/classes. More data on the susceptibility profile of Aspergillus spp. against the new classes of antifungal agents may allow for better treatment options and improved clinical outcomes in the coming years. In the meantime, continuous surveillance studies to monitor the prevalence of environmental and patient prevalence of azole resistance among Aspergillus spp. is absolutely crucial.

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Section: Epidemiology Of Azole-resistant a Fumigatusmentioning

confidence: 99%

Section: Diagnosis Of Azole-resistancementioning

confidence: 99%

Invasive Aspergillosis and the Impact of Azole-resistance

Bosetti

Neofytos

2023

Curr Fungal Infect Rep

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“…Aspergillus fumigatus is an opportunistic pathogen causing life-threatening infection in immunocompromised individuals ( Gülmez et al, 2021 ). These infections can lead to a variety of pulmonary fungal diseases including allergic bronchopulmonary aspergillosis, chronic pulmonary aspergillosis, and invasive pulmonary aspergillosis (IPA; Pasula and Chandrasekar, 2021 ). Among them, IPA is the most common invasive disease.…”

Section: Introductionmentioning

confidence: 99%

Antifungal Activity of Sodium New Houttuyfonate Against Aspergillus fumigatus in vitro and in vivo

et al. 2022

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Aspergillus fumigatus is an important pathogen causing invasive aspergillosis, which is associated with high morbidity and mortality in immunocompromised people. However, the treatment of A. fumigatus infection is a growing challenge, owing to the limited availability antifungal agents and the continual emergence of drug-resistant strains. Drug repurposing is a potential strategy to solve this current problem. Sodium new houttuyfonate (SNH), derived from houttuynin, extracted from Houttuynia cordata, has anti-bacterial and anti-Candida albicans effects. However, whether it has anti-A. fumigatus activity had not been reported. In this study, the antifungal properties of SNH against A. fumigatus, including the standard strain AF293, itraconazole resistant clinical strains, and voriconazole resistant clinical strains, were evaluated in vitro and in vivo. Moreover, the potential mechanism of SNH was characterized. SNH exhibited significant fungicidal activity toward various A. fumigatus strains. SNH also inhibited fungal growth, sporulation, conidial germination and pigment formation, and biofilm formation. Further investigations revealed that SNH interfered with the A. fumigatus cell steroid synthesis pathway, as indicated by transcriptomic and quantitative real-time polymerase chain reaction analyses, and inhibited ergosterol synthesis, as indicated by cell membrane stress assays and ergosterol quantification. Moreover, daily gastric gavage of SNH significantly decreased the fungal burden in mice with disseminated infection (kidney, liver, and lung) and local tissue damage. In addition, the application of SNH downregulated the production of IL-6 and IL-17A. Together, these findings provided the first confirmation that SNH may be a promising antifungal agent for the treatment of A. fumigatus infection.

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Efficacy and safety of Isavuconazole for the treatment of invasive Aspergillus infection - an update of the literature

Sivasubramanian

Chandrasekar

2022

Expert Opinion on Pharmacotherapy

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Azole resistance in Aspergillus species: promising therapeutic options

Cited by 6 publications

References 63 publications

Invasive Aspergillosis and the Impact of Azole-resistance

Invasive Aspergillosis and the Impact of Azole-resistance

Antifungal Activity of Sodium New Houttuyfonate Against Aspergillus fumigatus in vitro and in vivo

Efficacy and safety of Isavuconazole for the treatment of invasive Aspergillus infection - an update of the literature

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