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Advances in Antifungal Drugs
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Advances in Antifungal Drugs

A special issue of Journal of Fungi (ISSN 2309-608X). This special issue belongs to the section "Fungal Pathogenesis and Disease Control".

Deadline for manuscript submissions: closed (30 May 2024) | Viewed by 9720

Special Issue Editor

Dr. Iacopo Franconi

E-Mail Website
Guest Editor
Department of Translational Research and of New Technologies in Medicine and Surgery, University of Pisa, via San Zeno, 37, 56127 Pisa, Italy
Interests: Antifungal drugs; antifungal resistance; fungal diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Fungal infections cause milions of death world wide each year. Candida spp. and Aspergillus spp. are among the two principal opportunistic fungi associated with high mortality rates and detrimental impacts on healthcare resources. The population at risk of acquiring an invasive fungal infection is increasing at an alarming pace as the rates of antifungal resistance rise. This is primarily true in Candida spp., especially for azole resistance in Candida parapsilosis and echinocandin resistance in Candida glabrata, but also for azole resistance in Aspergillus fumigatus. In order to better highlight the magnitude of the problem, the WHO has recently released the fungal pathogen priority list to point out the direction future research should pursue. To this point, scholars should aim for the discovery of new molecules. The optimization of existing therapeutic strategies and the clinical evaluation of the potential and effectiveness of the new antifungal molecules recently introduced in the antifungal pipeline are of outmost importance and therefore will constitute the primary focus of this Special Issue.

Dr. Antonella Lupetti
Dr. Iacopo Franconi
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Fungi is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • new antifungal drugs
  • antifungal resistance
  • antifungal therapy
  • Candida spp. infections
  • Aspergillus spp. infections
  • fungal infections
  • antifungal compounds

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Published Papers (5 papers)

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Research

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21 pages, 6114 KiB  
Article
Unmasking the Antifungal Activity of Anacardium occidentale Leaf Extract against Candida albicans
by Luis F. Quejada, Andrea X. Hernandez, Luis C. Chitiva, Claudia P. Bravo-Chaucanés, Yerly Vargas-Casanova, Robson X. Faria, Geison M. Costa and Claudia M. Parra-Giraldo
J. Fungi 2024, 10(7), 464; https://doi.org/10.3390/jof10070464 - 29 Jun 2024
Cited by 1 | Viewed by 1418
Abstract
Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale [...] Read more.
Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Resistance to conventional antifungal drugs and the toxicity associated with high doses highlight the need for effective antifungal therapies. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed. Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. The doubling time was also drastically affected, going from 2.8 h to 22.5 h, which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cytotoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the potential mechanisms of A. occidentale against C. albicans on a cellular level, and might provide a promising option for the design of a new treatment for invasive candidiasis. Full article
(This article belongs to the Special Issue Advances in Antifungal Drugs)
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12 pages, 1598 KiB  
Article
In Vitro Activitiy of Rezafungin in Comparison with Anidulafungin and Caspofungin against Invasive Fungal Isolates (2017 to 2022) in China
by Simin Yang, Feifei Wan, Min Zhang, Huiping Lin, Liang Hu, Ziyi Zhou, Dongjiang Wang, Aiping Zhou, Lijun Ni, Jian Guo and Wenjuan Wu
J. Fungi 2024, 10(6), 397; https://doi.org/10.3390/jof10060397 - 31 May 2024
Viewed by 1061
Abstract
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 [...] Read more.
The efficacy of different echinocandins is assessed by evaluating the in vitro activity of a novel antifungal, rezafungin, against invasive fungal isolates in comparison with anidulafungin and caspofungin. Using the broth microdilution (BMD) method, the susceptibility of 1000 clinical Candida isolates (including 400 C. albicans, 200 C. glabrata, 200 C. parapsilosis, 150 C. tropicalis and 50 C. krusei) and 150 Aspergillus isolates (100 A. fumigatus and 50 A. flavus) from the Eastern China Invasive Fungi Infection Group (ECIFIG) was tested for the antifungals including anidulafungin, rezafungin, caspofungin and fluconazole. The echinocandins showed strong activity against C. albicans that was maintained against fluconazole-resistant isolates. The GM MIC (geometric mean minimum inhibitory concentration) value of rezafungin was found to be comparable to that of anidulafungin or caspofungin against the five tested common Candida species. C. tropicalis exhibited higher resistance rates (about 8.67–40.67% in different antifungals) than the other four Candida species. Through the sequencing of FKS genes, we searched for mutations in echinocandin-resistant C. tropicalis isolates and found that all displayed alterations in FKS1 S654P. The determined MEC (minimal effective concentration) values against A. fumigatus and A. flavus for rezafungin (0.116 μg/mL, 0.110 μg/mL) are comparable to those of caspofungin (0.122 μg/mL, 0.142 μg/mL) but higher than for anidulafungin (0.064 μg/mL, 0.059 μg/mL). Thus, the in vitro activity of rezafungin appears comparable to anidulafungin and caspofungin against most common Candida and Aspergillus species. Rezafungin showed higher susceptibility rates against C. glabrata. Rezafungin indicates its potent activity for potential clinical application. Full article
(This article belongs to the Special Issue Advances in Antifungal Drugs)
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17 pages, 6544 KiB  
Article
Unleashing Fungicidal Forces: Exploring the Synergistic Power of Amphotericin B-Loaded Nanoparticles and Monoclonal Antibodies
by Carla Soares de Souza, Victor Ropke da Cruz Lopes, Gabriel Barcellos, Francisco Alexandrino-Junior, Patrícia Cristina da Costa Neves, Beatriz Ferreira de Carvalho Patricio, Helvécio Vinícius Antunes Rocha, Ana Paula Dinis Ano Bom and Alexandre Bezerra Conde Figueiredo
J. Fungi 2024, 10(5), 344; https://doi.org/10.3390/jof10050344 - 10 May 2024
Cited by 1 | Viewed by 1273
Abstract
Fungal infections cause 1.7 million deaths annually, which can be attributed not only to fungus-specific factors, such as antifungal resistance and biofilm formation, but also to drug-related challenges. In this study, the potential of Amphotericin (AmB) loaded polymeric nanoparticles (AmB-NPs) combined with murine [...] Read more.
Fungal infections cause 1.7 million deaths annually, which can be attributed not only to fungus-specific factors, such as antifungal resistance and biofilm formation, but also to drug-related challenges. In this study, the potential of Amphotericin (AmB) loaded polymeric nanoparticles (AmB-NPs) combined with murine monoclonal antibodies (mAbs) (i.e., CC5 and DD11) was investigated as a strategy to overcome these challenges. To achieve this goal, AmB-NPs were prepared by nanoprecipitation using different polymers (polycaprolactone (PCL) and poly(D,L-lactide) (PLA)), followed by comprehensive characterization of their physicochemical properties and in vitro biological performance. The results revealed that AmB-loaded NPs exhibited no cytotoxicity toward mammalian cells (baby hamster kidney cells—BHK and human monocyte cells—THP-1). Conversely, both AmB-NPs demonstrated a cytotoxic effect against C. albicans, C. neoformans, and H. capsulatum throughout the entire evaluated range (from 10 µg/mL to 0.1 µg/mL), with a significant MIC of up to 0.031 µg/mL. Moreover, the combination of AmB-NPs with mAbs markedly intensified antifungal activity, resulting in a synergistic effect that was two to four times greater than that of AmB-NPs alone. These findings suggest that the combination of AmB-NPs with mAbs could be a promising new treatment for fungal infections that is potentially more effective and less toxic than current antifungal treatments. Full article
(This article belongs to the Special Issue Advances in Antifungal Drugs)
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Review

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19 pages, 789 KiB  
Review
Natural Substances as Valuable Alternative for Improving Conventional Antifungal Chemotherapy: Lights and Shadows
by Juan Carlos Argüelles, Ruth Sánchez-Fresneda, Alejandra Argüelles and Francisco Solano
J. Fungi 2024, 10(5), 334; https://doi.org/10.3390/jof10050334 - 5 May 2024
Cited by 1 | Viewed by 1893
Abstract
Fungi are eukaryotic organisms with relatively few pathogenic members dangerous for humans, usually acting as opportunistic infections. In the last decades, several life-threatening fungal infections have risen mostly associated with the worldwide extension of chronic diseases and immunosuppression. The available antifungal therapies cannot [...] Read more.
Fungi are eukaryotic organisms with relatively few pathogenic members dangerous for humans, usually acting as opportunistic infections. In the last decades, several life-threatening fungal infections have risen mostly associated with the worldwide extension of chronic diseases and immunosuppression. The available antifungal therapies cannot combat this challenge because the arsenal of compounds is scarce and displays low selective action, significant adverse effects, and increasing resistance. A growing isolation of outbreaks triggered by fungal species formerly considered innocuous is being recorded. From ancient times, natural substances harvested from plants have been applied to folk medicine and some of them recently emerged as promising antifungals. The most used are briefly revised herein. Combinations of chemotherapeutic drugs with natural products to obtain more efficient and gentle treatments are also revised. Nevertheless, considerable research work is still necessary before their clinical use can be generally accepted. Many natural products have a highly complex chemical composition, with the active principles still partially unknown. Here, we survey the field underlying lights and shadows of both groups. More studies involving clinical strains are necessary, but we illustrate this matter by discussing the potential clinical applications of combined carnosic acid plus propolis formulations. Full article
(This article belongs to the Special Issue Advances in Antifungal Drugs)
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22 pages, 2038 KiB  
Review
In Vitro Susceptibility Tests in the Context of Antifungal Resistance: Beyond Minimum Inhibitory Concentration in Candida spp.
by Iacopo Franconi and Antonella Lupetti
J. Fungi 2023, 9(12), 1188; https://doi.org/10.3390/jof9121188 - 12 Dec 2023
Cited by 3 | Viewed by 3246
Abstract
Antimicrobial resistance is a matter of rising concern, especially in fungal diseases. Multiple reports all over the world are highlighting a worrisome increase in azole- and echinocandin-resistance among fungal pathogens, especially in Candida species, as reported in the recently published fungal pathogens priority [...] Read more.
Antimicrobial resistance is a matter of rising concern, especially in fungal diseases. Multiple reports all over the world are highlighting a worrisome increase in azole- and echinocandin-resistance among fungal pathogens, especially in Candida species, as reported in the recently published fungal pathogens priority list made by WHO. Despite continuous efforts and advances in infection control, development of new antifungal molecules, and research on molecular mechanisms of antifungal resistance made by the scientific community, trends in invasive fungal diseases and associated antifungal resistance are on the rise, hindering therapeutic options and clinical cures. In this context, in vitro susceptibility testing aimed at evaluating minimum inhibitory concentrations, is still a milestone in the management of fungal diseases. However, such testing is not the only type at a microbiologist’s disposal. There are other adjunctive in vitro tests aimed at evaluating fungicidal activity of antifungal molecules and also exploring tolerance to antifungals. This plethora of in vitro tests are still left behind and performed only for research purposes, but their role in the context of invasive fungal diseases associated with antifungal resistance might add resourceful information to the clinical management of patients. The aim of this review was therefore to revise and explore all other in vitro tests that could be potentially implemented in current clinical practice in resistant and difficult-to-treat cases. Full article
(This article belongs to the Special Issue Advances in Antifungal Drugs)
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