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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 (31 July 2022) | Viewed by 18490

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Special Issue Editors

Prof. Dr. Suhail Ahmad

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Guest Editor

Department of Microbiology, Faculty of Medicine, Kuwait University, Kuwait
Interests: invasive candidiasis; invasive aspergillosis; diagnosis; molecular epidemiology; antifungal drug resistance; molecular mechanisms; emerging fungal pathogens; tuberculosis (TB) and other mycobacterial infections; epidemiology and diagnosis of TB and drug-resistant TB

Dr. Giuliana Lo Cascio

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Guest Editor

Microbiology Unit, Hospital Guglielmo da Saliceto, 29121 Piacenza, Italy
Interests: pathology; diagnostics; infectious diseases
Special Issues, Collections and Topics in MDPI journals

Dr. Saad J. Taj-Aldeen

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Guest Editor

Department of Laboratory Medicine and Pathology, Hamad medical Corporation, Doha, Qatar
Interests: clinical mycology; diagnostic microbiology; aspergillosis; candidemia; mucormycosis; fungal infections; filamentous fungi; infectious diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Invasive fungal infections (IFIs) are regarded as diseases of medical progress. With rapid changes in clinical practice and the expanding population of immunosuppressed/immunocompromised individuals, the spectrum of fungi capable of causing IFIs is also changing and expanding. Despite therapeutic advances, fungi constitute a major group of organisms associated with hospital-acquired infections worldwide and cause considerable morbidity and mortality, particularly among hospitalized patients with several comorbidities and other underlying conditions.

Candida and other yeast species colonize humans during or soon after birth and form part of normal microbial flora of skin and mucosal surfaces of the gastrointestinal and urogenital tracts. Similarly, colonization of the respiratory tract with Aspergillus species is common in normal healthy people. However, underlying conditions that compromise or suppress host immunity such as extremes of age (neonates and elderly individuals), pregnancy, diabetes, cancer, organ transplantation, and human immunodeficiency virus (HIV) infection predispose the colonized individuals to invasive infections by Candida species. Similarly, Aspergillus spp. colonization of the respiratory tract in immunocompromised/immunosuppressed patients is associated with severe disease including poorly controlled asthma, allergic bronchopulmonary aspergillosis, and invasive aspergillosis. Invasive infections due to other filamentous fungi constitute poorly investigated conditions, as many institutions have had limited experience with these infections. Hence, further studies focusing on the diagnosis, treatment, and prevention of these infections are urgently needed.

The control of IFIs is challenging due to increasing immunocompromised patient populations, emerging pathogenic species, and the increasing prevalence of fungal pathogen resistance to antifungal drugs, which potentially lead to diagnostic and therapeutic failures and increased healthcare costs. IFIs are associated with crude mortality rates of ~50%.

In this Special Issue on ‘Medical Health Care and Human Fungi’ we will focus on articles dealing with the diagnosis, epidemiology, and pathogenesis of IFIs in susceptible patients. Articles dealing with the mechanisms of antifungal drug resistance in common and rare/emerging fungal pathogens will also be welcome.

We look forward to your contributions.

Prof. Dr. Suhail Ahmad
Dr. Giuliana Lo Cascio
Dr. Saad J. Taj-Aldeen
Guest Editors

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

invasive candidiasis
invasive aspergillosis
conventional and molecular diagnostic approaches
molecular epidemiology
antifungal drug resistance
molecular mechanisms of antifungal drug resistance
emerging and novel fungal pathogens

Published Papers (8 papers)

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Research

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12 pages, 286 KiB

Open AccessArticle

A Regional Observational Study on COVID-19-Associated Pulmonary Aspergillosis (CAPA) within Intensive Care Unit: Trying to Break the Mold

by Tommaso Lupia, Giorgia Montrucchio, Alberto Gaviraghi, Gaia Musso, Mattia Puppo, Cesare Bolla, Nour Shbaklo, Barbara Rizzello, Andrea Della Selva, Erika Concialdi, Francesca Rumbolo, Anna Maria Barbui, Luca Brazzi, Francesco Giuseppe De Rosa and Silvia Corcione

J. Fungi 2022, 8(12), 1264; https://doi.org/10.3390/jof8121264 - 30 Nov 2022

Cited by 2 | Viewed by 1493

Abstract

The reported incidence of COVID-19-associated pulmonary aspergillosis (CAPA) ranges between 2.4% and 35% in intensive care unit (ICU) patients, and awareness in the medical community is rising. We performed a regional retrospective observational study including patients diagnosed with CAPA defined according to the Modified AspICU Dutch/Belgian Mycosis Study Group and CAPA–EECMM, from five different ICUs, admitted between March, 2020 and September, 2021. Forty-five patients were included. The median age was 64 (IQR 60–72), mostly (73%) males. At ICU admission, the median Charlson comorbidity index was 3 (2–5), and the simplified acute physiology score (SAPS)-II score was 42 (31–56). The main underlying diseases were hypertension (46%), diabetes (36%) and pulmonary diseases (15%). CAPA was diagnosed within a median of 17 days (IQR 10–21.75) after symptoms onset and 9 days (IQR 3–11) after ICU admission. The overall 28-day mortality rate was 58%, and at univariate analysis, it was significantly associated with older age (p = 0.009) and SAPS-II score at admission (p = 0.032). The use of immunomodulatory agents, p = 0.061; broad-spectrum antibiotics, p = 0.091; positive culture for Aspergillus on BAL, p = 0.065; and hypertension, p = 0.083, were near reaching statistical significance. None of them were confirmed in multivariate analysis. In critically ill COVID-19 patients, CAPA acquired clinical relevance in terms of incidence and reported mortality. However, the risk between underdiagnosis—in the absence of specific invasive investigations, and with a consequent possible increase in mortality—and over-diagnosis (case identification with galactomannan on broncho-alveolar fluid alone) might be considered. Realistic incidence rates, based on local, real-life epidemiological data, might be helpful in guiding clinicians. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

15 pages, 1955 KiB

Open AccessArticle

Combined Use of Presepsin and (1,3)-β-D-glucan as Biomarkers for Diagnosing Candida Sepsis and Monitoring the Effectiveness of Treatment in Critically Ill Patients

by Radim Dobiáš, Marcela Káňová, Naděžda Petejová, Štefan Kis Pisti, Robert Bocek, Eva Krejčí, Helena Stružková, Michaela Cachová, Hana Tomášková, Petr Hamal, Vladimír Havlíček and Milan Raška

J. Fungi 2022, 8(3), 308; https://doi.org/10.3390/jof8030308 - 17 Mar 2022

Cited by 3 | Viewed by 2751

Abstract

New biomarker panel was developed and validated on 165 critically ill adult patients to enable a more accurate invasive candidiasis (IC) diagnosis. Serum levels of the panfungal biomarker (1,3)-β-D-glucan (BDG) and the inflammatory biomarkers C-reactive protein, presepsin (PSEP), and procalcitonin (PCT) were correlated with culture-confirmed candidemia or bacteremia in 58 and 107 patients, respectively. The diagnostic utility was evaluated in sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). BDG was the best marker for IC, achieving 96.6% sensitivity, 97.2% specificity, 94.9% PPV, and 98.1% NPV at a cut-off of 200 pg/mL (p ≤ 0.001). PSEP exhibited 100% sensitivity and 100% NPV at a cut-off of 700 pg/mL but had a lower PPV (36.5%) and low specificity (5.6%). Combined use of PSEP and BDG, thus, seems to be the most powerful laboratory approach for diagnosing IC. Furthermore, PSEP was more accurate for 28-day mortality prediction the area under the receiver operating characteristic curve (AUC = 0.74) than PCT (AUC = 0.31; PCT cut-off = 0.5 ng/mL). Finally, serum PSEP levels decreased significantly after only 14 days of echinocandin therapy (p = 0.0012). The probability of IC is almost 100% in critically ill adults with serum BDG and PSEP concentrations > 200 pg/mL and >700 pg/mL, respectively, defining a borderline between non-invasive superficial Candida colonization and IC. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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11 pages, 653 KiB

Open AccessArticle

Incidence of Chronic Pulmonary Aspergillosis in Patients with Suspected or Confirmed NTM and TB—A Population-Based Retrospective Cohort Study

by Frederik P. Klinting, Christian B. Laursen and Ingrid L. Titlestad

J. Fungi 2022, 8(3), 301; https://doi.org/10.3390/jof8030301 - 16 Mar 2022

Cited by 1 | Viewed by 2475

Abstract

Chronic pulmonary aspergillosis (CPA) is a severe and underdiagnosed pulmonary fungal infection with a significant overlap in symptoms and imaging findings of mycobacterium tuberculosis (TB) and non-tuberculous mycobacterium (NTM). Infection with TB or NTM is a predisposing underlying condition for CPA in approximately one-third of patients. A previously published study from Uganda showed increased incidence and complication rate of CPA with respect to pre-existing radiographic cavitation in a post-treatment TB population. The aim of this study was to investigate the incidence of CPA in a low-endemic population of confirmed or suspected TB and NTM patients. We manually reviewed 172 patients referred on suspicion or for treatment of TB or NTM at the Department of Respiratory Medicine, Odense University Hospital during the period of 1 January 2018 to 31 December 2020. We found no CPA amongst TB patients as opposed to an incidence of 8.2% (n = 4) in NTM-infected patients. We identified possible investigatory differences in Aspergillus blood sample screening protocols depending on NTM or TB, initiated at the Department of Respiratory Medicine at Odense University Hospital. A focused screening and investigatory protocol in NTM patients with persisting or developing symptoms is warranted in relation to suspected CPA. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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14 pages, 515 KiB

Open AccessArticle

Prevalence of Chronic Pulmonary Aspergillosis in Patients Suspected of Chest Malignancy

by Rasmus Rønberg, Jesper Rømhild Davidsen, Helmut J. F. Salzer, Eva Van Braeckel, Flemming Schønning Rosenvinge and Christian B. Laursen

J. Fungi 2022, 8(3), 297; https://doi.org/10.3390/jof8030297 - 13 Mar 2022

Cited by 4 | Viewed by 2673

Abstract

Chronic pulmonary aspergillosis (CPA) is a potentially life-threatening fungal lung infection, and recent research suggests CPA to be more common than previously considered. Although CPA mimics other lung diseases including pulmonary cancer, awareness of this disease entity is still sparse. This study aimed to investigate the prevalence of CPA in a population of patients under suspicion of having lung cancer. We conducted a retrospective cohort study of 1200 patients and manually collected individual health record data from previous cancer examinations, with retrospective CPA status assessment using international criteria. Among 992 included patients, 16 (1.6%) fulfilled diagnostic criteria for CPA retrospectively, of whom 15 were undiscovered at initial lung cancer examination. The prevalence of CPA in this study population was 50 times higher than the reported prevalence of the overall European population. Our findings indicate that CPA is often missed in patients suspected of malignancy in the chest. Therefore, CPA should be kept in mind as a significant differential diagnosis. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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Review

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30 pages, 1775 KiB

Open AccessReview

Novel Treatment Approach for Aspergilloses by Targeting Germination

by Kim Verburg, Jacq van Neer, Margherita Duca and Hans de Cock

J. Fungi 2022, 8(8), 758; https://doi.org/10.3390/jof8080758 - 22 Jul 2022

Cited by 9 | Viewed by 3144

Abstract

Germination of conidia is an essential process within the Aspergillus life cycle and plays a major role during the infection of hosts. Conidia are able to avoid detection by the majority of leukocytes when dormant. Germination can cause severe health problems, specifically in immunocompromised people. Aspergillosis is most often caused by Aspergillus fumigatus (A. fumigatus) and affects neutropenic patients, as well as people with cystic fibrosis (CF). These patients are often unable to effectively detect and clear the conidia or hyphae and can develop chronic non-invasive and/or invasive infections or allergic inflammatory responses. Current treatments with (tri)azoles can be very effective to combat a variety of fungal infections. However, resistance against current azoles has emerged and has been increasing since 1998. As a consequence, patients infected with resistant A. fumigatus have a reported mortality rate of 88% to 100%. Especially with the growing number of patients that harbor azole-resistant Aspergilli, novel antifungals could provide an alternative. Aspergilloses differ in defining characteristics, but germination of conidia is one of the few common denominators. By specifically targeting conidial germination with novel antifungals, early intervention might be possible. In this review, we propose several morphotypes to disrupt conidial germination, as well as potential targets. Hopefully, new antifungals against such targets could contribute to disturbing the ability of Aspergilli to germinate and grow, resulting in a decreased fungal burden on patients. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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Other

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7 pages, 403 KiB

Open AccessBrief Report

Sensitivity of Serum Beta-D-Glucan in Candidemia According to Candida Species Epidemiology in Critically Ill Patients Admitted to the Intensive Care Unit

by Malgorzata Mikulska, Laura Magnasco, Alessio Signori, Chiara Sepulcri, Silvia Dettori, Stefania Tutino, Antonio Vena, Franca Miletich, Nadir Ullah, Paola Morici, Lorenzo Ball, Paolo Pelosi, Anna Marchese, Daniele Roberto Giacobbe and Matteo Bassetti

J. Fungi 2022, 8(9), 921; https://doi.org/10.3390/jof8090921 - 30 Aug 2022

Cited by 15 | Viewed by 1802

Abstract

Serum beta-D-glucan (BDG) determination plays an important role in the diagnosis of candidemia among critically ill patients admitted to the intensive care unit (ICU). However, BDG levels measured may be lower in the case of infections caused by some non-albicans species, such as C. parapsilosis and C. auris. The aim of this single-center study was to investigate the sensitivity of serum BDG for the diagnosis of candidemia stratified according to causative Candida species in ICU patients. This was a single-center, retrospective study, including all adult patients admitted to ICU during the period 2018–2021. All episodes of candidemia with a determination of BDG available within 3 days before or after positive blood culture were recorded. The preplanned primary objective was to investigate the sensitivity of serum BDG to detect candidemia early and the effect of different Candida species. The secondary objective was to measure serum BDG in patients with candidemia from different Candida species. In total, 146 candidemia episodes in 118 patients were analyzed. Median BDG value for C. albicans candidemia (182 pg/mL) was higher than that observed for C. parapsilosis (78 pg/mL, p = 0.015) and C. auris (48 pg/mL, p = 0.022). The overall sensitivity of BDG for the diagnosis of candidemia was low (47%, 95% CI 39–55%). In conclusion, in critically ill patients admitted to ICU, serum BDG levels for candidemia were different among species, with lower levels confirmed for C. parapsilosis and C. auris. Serum BDG sensitivity for early detection of candidemia was lower than previously reported in other ICU populations. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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13 pages, 1329 KiB

Open AccessSystematic Review

Periprosthetic Joint Infections Caused by Candida Species—A Single-Center Experience and Systematic Review of the Literature

by Dariusz Grzelecki, Aleksandra Grajek, Piotr Dudek, Łukasz Olewnik, Nicol Zielinska, Petr Fulin, Maria Czubak-Wrzosek, Marcin Tyrakowski, Dariusz Marczak and Jacek Kowalczewski

J. Fungi 2022, 8(8), 797; https://doi.org/10.3390/jof8080797 - 29 Jul 2022

Cited by 3 | Viewed by 1571

Abstract

Background: The aim of this study was to analyze the treatment results of fungal periprosthetic joint infections (PJI) caused by Candida species from a single orthopedic center and to compare them with reports from other institutions. Methods: Eight patients operated on from January 2014 to December 2021 met the inclusion criteria and were analyzed in terms of clinical outcomes. A systematic review of the literature identified 153 patients with Candida PJIs extracted from 12 studies according to the PRISMA (Preferred Reporting Item for Systematic Reviews and Meta-Analyses) guidelines. Results: The success rate of the treatment in the case series was 50%. The most frequent pathogens were Candida albicans (three cases; 37.5%) and Candida parapsilosis (three cases; 37.5%). In one patient (12.5%), bacterial co-infection was noted, and in five patients (62.5%) significant risk factors of PJI were confirmed. The overall success rate on the basis of data collected for systematic review was 65.5%. A sub-analysis of 127 patients revealed statistically significant differences (p = 0.02) with a higher success rate for the knees (77.6%) than for the hips (58%). In 10 studies the analysis of risk factors was performed and among 106 patients in 77 (72.6%) comorbidities predispose to fungal PJI were confirmed. Bacterial co-infection was noted in 84 patients (54.9%). In 93 patients (60.7%) Candida albicans was the culprit pathogen, and in 39 patients (25.5%) Candida parapsilosis was the culprit pathogen. Based on these two most frequent Candida species causing PJI, the success rate of the treatment was statistically different (p = 0.03), and was 60.3% and 83.3%, respectively. The two-stage strategy was more favorable for patients with Candida parapsilosis infections (94.4% success rate) than the one-stage protocol (50% success rate; p = 0.02); as well as in comparison to the two-stage treatment of Candida albicans (65% success rate; p = 0.04). Conclusions: The analysis of the literature showed no differences in the overall success rate between one- and two-stage surgical strategies for all Candida species, but differed significantly comparing the two most frequent strains and concerning PJI localization. The frequent presence of bacterial co-infections makes it necessary to consider the additional administration of antibiotics in the case of fungal PJI. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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7 pages, 572 KiB

Open AccessBrief Report

Comparison of Antimycotic Activity of Originator and Generics of Voriconazole and Anidulafungin against Clinical Isolates of Candida albicans and Candida glabrata

by Alina Karoline Nussbaumer-Pröll, Sabine Eberl, René Welte, Tiziana Gasperetti, Jana Marx, Romuald Bellmann and Markus Zeitlinger

J. Fungi 2022, 8(2), 195; https://doi.org/10.3390/jof8020195 - 17 Feb 2022

Cited by 2 | Viewed by 1436

Abstract

Background: Concerns have been expressed about the interchangeability of innovator and generic antifungals in their activity and chemical stability. Materials/methods: The activity of two different antimycotics was tested, each with one originator and two generics. For voriconazole, the originator VFEND^® (Pfizer) and the generics (Ratiopharm and Stada) were used for susceptibility testing (21 clinical isolates of Candida albicans (C. albicans); ATCC-90028 C. albicans) in RPMI growth media in compliance with the EUCAST criteria. Likewise, for anidulafungin, the originator ECALTA^® (Pfizer) and the generics (Stada and Pharmore) were used for testing (20 clinical isolates of Candida glabrata (C. glabrata); ATCC-22019 Candida parapsilosis (C. parapsilosis)). Time Kill Curves (TKC) with concentrations above and below the respective MIC were performed for one strain for each antifungal. Stability testing of the antimycotics stored at 4 °C and at room temperature over 24 h was done, and samples were subsequently analyzed with HPLC. Results: MIC results showed no significant difference in activity of generic and innovator antimycotic in all settings, which was also confirmed by TKC. Stability testing revealed no differences between originator and generic drugs. Conclusions: The present study demonstrates the interchangeability of generic and originator antimycotic in-vitro, potentially leading to broader public acceptance for generic antimycotics. Full article

(This article belongs to the Special Issue Medical Health Care and Human Fungi)

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