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Antifungal Drugs 2022
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Antifungal Drugs 2022

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 (15 March 2023) | Viewed by 12906

Special Issue Editor

Prof. Dr. Susumu Kajiwara

E-Mail Website
Guest Editor
School of Life Science and Technolgy, Tokyo Institute of Technology, Yokohama, Japan
Interests: medical mycology; fungal infections; fungal immunology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Compared to many kinds of antibiotics for bacteria, antifungal drugs used for treating fungal infections in clinics and hospitals are limited. Antifungal drugs such as azoles, echinocandins, and polyenes are currently used for the treatment of invasive fungal infections caused by pathogens entering the human bloodstream, central nervous system, and organs such as liver and lungs, sometimes leading to life-threatening diseases to immunocompromised and immunosuppressed individuals. However, some of these antifungals are known to participate in drug–drug interactions and cause serious side effects. In addition, the antifungal and multidrug resistances of opportunistic fungi, including Aspergillus fumigatus, Candida albicans, and Cryptococcus neoformans, have increased and become a significant burden in clinical sites in the world. Recently, emerging fungal species such as C. auris were isolated, and some of their strains also show antifungal and multi-drug resistances.

The aim of this Special Issue is to highlight current research and the development of novel antifungal drugs and drug resistances in invasive fungal infection to humans.

Prof. Dr. Susumu Kajiwara
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

  • antifungals
  • antifungal drug resistance
  • multidrug resistance of fungal pathogens
  • drug resistance of emerging fungi

Related Special Issue

Published Papers (5 papers)

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Research

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13 pages, 5024 KiB  
Article
In Candida glabrata, ERMES Component GEM1 Controls Mitochondrial Morphology, mtROS, and Drug Efflux Pump Expression, Resulting in Azole Susceptibility
by Michiyo Okamoto, Keiko Nakano, Azusa Takahashi-Nakaguchi, Kaname Sasamoto, Masashi Yamaguchi, Miguel Cacho Teixeira and Hiroji Chibana
J. Fungi 2023, 9(2), 240; https://doi.org/10.3390/jof9020240 - 10 Feb 2023
Cited by 3 | Viewed by 1793
Abstract
Mitochondrial dysfunction or morphological abnormalities in human pathogenic fungi are known to contribute to azole resistance; however, the underlying molecular mechanisms are unknown. In this study, we investigated the link between mitochondrial morphology and azole resistance in Candida glabrata, which is the [...] Read more.
Mitochondrial dysfunction or morphological abnormalities in human pathogenic fungi are known to contribute to azole resistance; however, the underlying molecular mechanisms are unknown. In this study, we investigated the link between mitochondrial morphology and azole resistance in Candida glabrata, which is the second most common cause of human candidiasis worldwide. The ER-mitochondrial encounter structure (ERMES) complex is thought to play an important role in the mitochondrial dynamics necessary for mitochondria to maintain their function. Of the five components of the ERMES complex, deletion of GEM1 increased azole resistance. Gem1 is a GTPase that regulates the ERMES complex activity. Point mutations in GEM1 GTPase domains were sufficient to confer azole resistance. The cells lacking GEM1 displayed abnormalities in mitochondrial morphology, increased mtROS levels, and increased expression of azole drug efflux pumps encoded by CDR1 and CDR2. Interestingly, treatment with N-acetylcysteine (NAC), an antioxidant, reduced ROS production and the expression of CDR1 in Δgem1 cells. Altogether, the absence of Gem1 activity caused an increase in mitochondrial ROS concentration, leading to Pdr1-dependent upregulation of the drug efflux pump Cdr1, resulting in azole resistance. Full article
(This article belongs to the Special Issue Antifungal Drugs 2022)
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17 pages, 306 KiB  
Article
Comparing the Real-World Use of Isavuconazole to Other Anti-Fungal Therapy for Invasive Fungal Infections in Patients with and without Underlying Disparities: A Multi-Center Retrospective Study
by Marjorie Vieira Batista, Maria Piedad Ussetti, Ying Jiang, Dionysios Neofytos, Anita Cassoli Cortez, Diego Feriani, Jayr Schmidt-Filho, Ivan Leonardo Avelino França-Silva, Issam Raad and Ray Hachem
J. Fungi 2023, 9(2), 166; https://doi.org/10.3390/jof9020166 - 27 Jan 2023
Cited by 4 | Viewed by 2475
Abstract
Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with underlying malignancies and prior transplants. FDA approved Isavuconazole as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. This study aims to compare the real-world clinical outcomes [...] Read more.
Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with underlying malignancies and prior transplants. FDA approved Isavuconazole as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. This study aims to compare the real-world clinical outcomes and safety of isavuconazole to voriconazole and an amphotericin B-based regimen in patients with underlying malignancies and a transplant. In addition, the response to anti-fungal therapy and the outcome were compared among patients with a disparity (elderly, obese patients, patients with renal insufficiency and diabetes mellitus) versus those with no disparity. We performed a multicenter retrospective study, including patients with cancer diagnosed with an invasive fungal infection, and treated primarily with isavuconazole, voriconazole or amphotericin B. Clinical, radiologic findings, response to therapy and therapy related adverse events were evaluated during 12 weeks of follow-up. We included 112 patients aged 14 to 77 years, and most of the IFIs were classified into definite (29) or probable (51). Most cases were invasive aspergillosis (79%), followed by fusariosis (8%). Amphotericin B were used more frequently as primary therapy (38%) than isavuconazole (30%) or voriconazole (31%). Twenty one percent of the patients presented adverse events related to primary therapy, with patients receiving isavuconazole presenting less adverse events when compared to voriconazole and amphotericin (p < 0.001; p = 0.019). Favorable response to primary therapy during 12 weeks of follow-up were similar when comparing amphotericin B, isavuconazole or voriconazole use. By univariate analysis, the overall cause of mortality at 12 weeks was higher in patients receiving amphotericin B as primary therapy. However, by multivariate analysis, Fusarium infection, invasive pulmonary infection or sinus infection were the only independent risk factors associated with mortality. In the treatment of IFI for patients with underlying malignancy or a transplant, Isavuconazole was associated with the best safety profile compared to voriconazole or amphotericin B-based regimen. Regardless of the type of anti-fungal therapy used, invasive Fusarium infections and invasive pulmonary or sinus infections were the only risk factors associated with poor outcomes. Disparity criteria did not affect the response to anti-fungal therapy and overall outcome, including mortality. Full article
(This article belongs to the Special Issue Antifungal Drugs 2022)
14 pages, 1114 KiB  
Article
Unravelling the Molecular Identification and Antifungal Susceptibility Profiles of Aspergillus spp. Isolated from Chronic Pulmonary Aspergillosis Patients in Jakarta, Indonesia: The Emergence of Cryptic Species
by Anna Rozaliyani, Asriyani Abdullah, Findra Setianingrum, Wellyzar Sjamsuridzal, Retno Wahyuningsih, Anom Bowolaksono, Ayu Eka Fatril, Robiatul Adawiyah, Mulyati Tugiran, Ridhawati Syam, Heri Wibowo, Chris Kosmidis and David W. Denning
J. Fungi 2022, 8(4), 411; https://doi.org/10.3390/jof8040411 - 16 Apr 2022
Cited by 3 | Viewed by 2982
Abstract
Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the [...] Read more.
Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the management of CPA. The aim of this study was to describe the molecular and susceptibility profiles of Aspergillus isolated from CPA patients. The species identity of isolates was determined by combined DNA analyses of internal transcribed space (ITS), partial β-tubulin genes, and part of the calmodulin gene. We revealed a high (27%) prevalence of cryptic species among previous tuberculosis patients with persistent symptoms. Twenty-nine (49%) patients met the criteria for diagnosis of CPA with 24% containing Aspergillus cryptic species. This is the first report of five cryptic Aspergillus species from clinical isolates in Indonesia: A. aculea tus, A. neoniger, A. brunneoviolacues, A. welwitschiae, and A. tubingensis. Significantly, there was decreased sensitivity against itraconazole in the CPA group (66% susceptible to itraconazole) compared to the non-CPA group (90% susceptible to itraconazole) (p = 0.003). The species-level characterisation of Aspergillus and its antifungal susceptibility tests demands greater attention to better the management of CPA patients. Full article
(This article belongs to the Special Issue Antifungal Drugs 2022)
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Review

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10 pages, 299 KiB  
Review
Marine Compounds with Anti-Candida sp. Activity: A Promised “Land” for New Antifungals
by Anelise Maria Costa Vasconcelos Alves, Natália Cruz-Martins and Célia Fortuna Rodrigues
J. Fungi 2022, 8(7), 669; https://doi.org/10.3390/jof8070669 - 25 Jun 2022
Cited by 6 | Viewed by 1936
Abstract
Candida albicans is still the major yeast causing human fungal infections. Nevertheless, in the last decades, non-Candida albicans Candida species (NCACs) (e.g., Candida glabrata, Candida tropicalis, and Candida parapsilosis) have been increasingly linked to Candida sp. infections, mainly in [...] Read more.
Candida albicans is still the major yeast causing human fungal infections. Nevertheless, in the last decades, non-Candida albicans Candida species (NCACs) (e.g., Candida glabrata, Candida tropicalis, and Candida parapsilosis) have been increasingly linked to Candida sp. infections, mainly in immunocompromised and hospitalized patients. The escalade of antifungal resistance among Candida sp. demands broadly effective and cost-efficient therapeutic strategies to treat candidiasis. Marine environments have shown to be a rich source of a plethora of natural compounds with substantial antimicrobial bioactivities, even against resistant pathogens, such as Candida sp. This short review intends to briefly summarize the most recent marine compounds that have evidenced anti-Candida sp. activity. Here, we show that the number of compounds discovered in the last years with antifungal activity is growing. These drugs have a good potential to be used for the treatment of candidiasis, but disappointedly the reports have devoted a high focus on C. albicans, neglecting the NCACs, highlighting the need to perform outspreading studies in the near future. Full article
(This article belongs to the Special Issue Antifungal Drugs 2022)

Other

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10 pages, 1130 KiB  
Brief Report
Lack of Association between YEASTONE Antifungal Susceptibility Tests and Clinical Outcomes of Cryptococcus Meningitis
by Ting-Shu Wu, Jung-Fu Lin, Chun-Wen Cheng, Po-Yen Huang and Jeng-How Yang
J. Fungi 2023, 9(2), 232; https://doi.org/10.3390/jof9020232 - 10 Feb 2023
Cited by 2 | Viewed by 1299
Abstract
The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. [...] Read more.
The relation between antifungal susceptibility and treatment outcomes is not well-characterized. There is paucity of surveillance data for cerebrospinal fluid (CSF) isolates of cryptococcus investigated with YEASTONE colorimetric broth microdilution susceptibility testing. A retrospective study of laboratory-confirmed cryptococcus meningitis (CM) patients was conducted. The antifungal susceptibility of CSF isolates was determined using YEASTONE colorimetric broth microdilution. Clinical parameters, CSF laboratory indices, and antifungal susceptibility results were analyzed to identify risk factors for mortality. High rates of resistance to fluconazole and flucytosine were observed in this cohort. Voriconazole had the lowest MIC (0.06 µg/mL) and lowest rate of resistance (3.8%). In a univariate analysis, hematological malignancy, concurrent cryptococcemia, high Sequential Organ Failure Assessment (SOFA) score, low Glasgow coma scale (GCS) score, low CSF glucose level, high CSF cryptococcal antigen titer, and high serum cryptococcal antigen burden were associated with mortality. In a multivariate analysis, meningitis with concurrent cryptococcemia, GCS score, and high CSF cryptococcus burden, were independent predictors of poor prognosis. Both early and late mortality rates were not significantly different between CM wild type and non-wild type species. Full article
(This article belongs to the Special Issue Antifungal Drugs 2022)
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