Advances in Fungal Infections: Special Issue in Diagnostics Journal-Volume 2

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Diagnostic Microbiology and Infectious Disease".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 20473

Special Issue Editors


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Guest Editor
1. National Centre for Radiotherapy Oncology and Nuclear Medicine, Korle Bu Teaching Hospital, P.O. Box KB369, Korle Bu, GA-222 7974 Accra, Ghana
2. Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
3. Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Private Bag X169, Pretoria 0001, South Africa
Interests: PET/CT imaging; fungal infections; tuberculosis; human immunodeficiency virus
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Guest Editor
Medical Imaging Center, Department of Nuclear Medicine & Molecular Imaging, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands
Interests: infections; inflammatory diseases; PET/CT; imaging; (tumor)immunology; multimodality imaging
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
1. Department of Nuclear Medicine, University of Pretoria, Pretoria, South Africa
2. Nuclear Medicine Research Infrastructure, Steve Biko Academic Hospital, Pretoria, South Africa
Interests: radionuclide therapy; radiobiology; theranostics; targeted alpha therapy; radionuclide imaging; inflammation and infection imaging; tuberculosis; HIV; fungal infections; prostate cancer; neuroendocrine tumors; novel radiopharmaceutical design; machine learning
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Fungi are ubiquitous in the environment and occur as commensals in the flora of mucosal surfaces of mammalian tissues. Fungal infections, however, cause severe morbidity and mortality, particularly in immunocompromised patients and seriously ill patients. In fact, some epidemiologists have even projected that a fungus may be the next cause of a pandemic after COVID-19.

To be prepared to stop or contain the potential havoc that fungi may cause, it is important to understand their emerging epidemiological patterns, the mechanisms underlying their microbiology, and their drug-resistance mechanisms, in order to discuss all available techniques for diagnosis and treatment, and to explore new diagnostic and therapeutic interventions. It is important that the different disciplines that work on different aspects of fungi pull their resources and expertise together to overcome the current and potential threats posed by fungal infections.

In this Special Issue on fungi, we invite reviews and original articles that include—but are not limited to—the following:

  1. Advances in our knowledge of the genetics and the microbiologic mechanisms by which fungi resist destruction.
  2. New insights in human immune response, and the mechanisms by which fungi are able to evade this.
  3. New diagnostic and therapeutic platforms in managing these fungal infections.
  4. New paradigms of multidisciplinary management of fungal infections.
  5. Potential therapeutic strategies that may augment the current strategies.

Dr. Alfred O. Ankrah
Prof. Dr. Andor W.J.M. Glaudemans
Prof. Dr. Mike M. Sathekge
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. Diagnostics is an international peer-reviewed open access semimonthly 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

  • mycosis
  • invasive fungal infections
  • antifungal agents
  • galactomannan
  • β-D-glycan
  • antifungal stewardship
  • computed tomography
  • monitoring antifungal treatment
  • blood stream infections
  • molecular testing

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Published Papers (8 papers)

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Research

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10 pages, 511 KiB  
Article
Different BD BACTEC Blood Culture Bottle Types for the Detection of Fungi in Simulated Sterile Body Fluid Samples
by Rok Tomazin, Tadej Pliberšek, Anja Oštrbenk Valenčak and Tadeja Matos
Diagnostics 2023, 13(10), 1699; https://doi.org/10.3390/diagnostics13101699 - 11 May 2023
Viewed by 2414
Abstract
Blood culture systems are a potential alternative to classical cultivation of fungi on mycological media, but there are limited data on the suitability of these systems for culturing other sample types (e.g., sterile body fluids). We conducted a prospective study to evaluate different [...] Read more.
Blood culture systems are a potential alternative to classical cultivation of fungi on mycological media, but there are limited data on the suitability of these systems for culturing other sample types (e.g., sterile body fluids). We conducted a prospective study to evaluate different types of blood culture (BC) bottles for the detection of different fungal species in non-blood samples. A total of 43 fungal isolates were tested for their ability to grow in BD BACTEC Mycosis-IC/F (Mycosis bottles), BD BACTEC Plus Aerobic/F (Aerobic bottles) and BD BACTEC Plus Anaerobic/F (Anaerobic bottles) (Becton Dickinson, East Rutherford, NJ, USA) BC bottles inoculated with spiked samples without the addition of blood or fastidious organism supplement. Time to detection (TTD) was determined for all BC types tested and compared between groups. In general, Mycosis and Aerobic bottles were similar (p > 0.05). The Anaerobic bottles failed to support growth in >86% of cases. The Mycosis bottles were superior in detecting Candida glabrata, Cryptococcus spp. and Aspergillus spp. (p < 0.05). The performance of Mycosis and Aerobic bottles was similar, but if cryptococcosis or aspergillosis is suspected, the use of Mycosis bottles is recommended. Anaerobic bottles are not recommended for fungal detection. Full article
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9 pages, 8602 KiB  
Communication
Usefulness of Chromogenic Media with Fluconazole Supplementation for Presumptive Identification of Candida auris
by Alba Ruiz-Gaitán, Ignacio Sigona-Giangreco, José Manuel Pérez-Royo, Victor Garcia-Bustos, Marta García-Hita, Eulogio Valentín-Gómez, Salvador Giner Almaraz, Piet W. J. de Groot and Javier Pemán
Diagnostics 2023, 13(2), 231; https://doi.org/10.3390/diagnostics13020231 - 8 Jan 2023
Cited by 1 | Viewed by 5590
Abstract
Introduction:Candida auris is a major threat to public health. Rapid detection is essential for early treatment and transmission control. The use of chromogenic media allows the presumptive identification of this new species. The aim of this study is to describe the [...] Read more.
Introduction:Candida auris is a major threat to public health. Rapid detection is essential for early treatment and transmission control. The use of chromogenic media allows the presumptive identification of this new species. The aim of this study is to describe the morphological characteristics of C. auris colonies on three commercial chromogenic media. Methods: Nineteen C. auris isolates from different countries/clades and 18 isolates of other species were cultivated in CHROMagarTM Candida Plus, HiCromeTM Candida, CHROMagar-Candida, and fluconazole-supplemented (32 mg/L) CHROMagar-Candida media. Results: On CHROMagarTM Candida Plus and HiCromeTM Candida, C. auris isolates from Colombia, Venezuela, India, Korea, and Japan displayed blue-shaded colonies, while isolates from Spain and Germany exhibited light pink shades with a bluish halo. All isolates showed white to pink colonies on CHROMagar-Candida. On CHROMagar Candida supplemented with fluconazole, whilst C. auris, C. glabrata, or C. krusei showed a similar pink color at 48 h incubation, phenotypic differentiation was possible by the rough, paraffin-like texture or the intense purple color acquired by C. krusei and C. glabrata, respectively. Moreover, in this medium, the presence of C. auris in combination with other species of similar color was not limiting for its early identification, due to this medium selecting only strains resistant to this antifungal. Conclusions: The use of chromogenic media such as CHROMagarTM Candida Plus facilitates a presumptive identification of C. auris. However, this identification can be difficult in the presence of mixed cultures. In these cases, the use of CHROMagarTM Candida medium with 32 mg/L fluconazole offers better performance for the identification of C. auris by inhibiting fluconazole-susceptible strains and selecting rare or high fluconazole MIC (>32 mg/L) isolates. Full article
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16 pages, 3459 KiB  
Article
An Alternative Diagnostic Method for C. neoformans: Preliminary Results of Deep-Learning Based Detection Model
by Ayse Seyer Cagatan, Mubarak Taiwo Mustapha, Cemile Bagkur, Tamer Sanlidag and Dilber Uzun Ozsahin
Diagnostics 2023, 13(1), 81; https://doi.org/10.3390/diagnostics13010081 - 28 Dec 2022
Cited by 4 | Viewed by 3325
Abstract
Cryptococcus neoformans is an opportunistic fungal pathogen with significant medical importance, especially in immunosuppressed patients. It is the causative agent of cryptococcosis. An estimated 220,000 annual cases of cryptococcal meningitis (CM) occur among people with HIV/AIDS globally, resulting in nearly 181,000 deaths. The [...] Read more.
Cryptococcus neoformans is an opportunistic fungal pathogen with significant medical importance, especially in immunosuppressed patients. It is the causative agent of cryptococcosis. An estimated 220,000 annual cases of cryptococcal meningitis (CM) occur among people with HIV/AIDS globally, resulting in nearly 181,000 deaths. The gold standards for the diagnosis are either direct microscopic identification or fungal cultures. However, these diagnostic methods need special types of equipment and clinical expertise, and relatively low sensitivities have also been reported. This study aims to produce and implement a deep-learning approach to detect C. neoformans in patient samples. Therefore, we adopted the state-of-the-art VGG16 model, which determines the output information from a single image. Images that contain C. neoformans are designated positive, while others are designated negative throughout this section. Model training, validation, testing, and evaluation were conducted using frameworks and libraries. The state-of-the-art VGG16 model produced an accuracy and loss of 86.88% and 0.36203, respectively. Results prove that the deep learning framework VGG16 can be helpful as an alternative diagnostic method for the rapid and accurate identification of the C. neoformans, leading to early diagnosis and subsequent treatment. Further studies should include more and higher quality images to eliminate the limitations of the adopted deep learning model. Full article
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8 pages, 256 KiB  
Article
Candida Species Isolation from Hospitalized Patients with COVID-19—A Retrospective Study
by Petros Ioannou, Diamantis P. Kofteridis, Konstantinos Alexakis, Christos Koutserimpas, Ioanna Papakitsou, Sofia Maraki and George Samonis
Diagnostics 2022, 12(12), 3065; https://doi.org/10.3390/diagnostics12123065 - 6 Dec 2022
Cited by 2 | Viewed by 1021
Abstract
Coronavirus disease 2019 (COVID-19), a disease characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has so far led to hundreds of millions of infections and millions of deaths. Fungal infections are known to complicate COVID-19 patients and are associated with significant morbidity [...] Read more.
Coronavirus disease 2019 (COVID-19), a disease characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has so far led to hundreds of millions of infections and millions of deaths. Fungal infections are known to complicate COVID-19 patients and are associated with significant morbidity and mortality. The aim of this study was to assess the incidence of positive cultures for Candida spp. among patients hospitalized with COVID-19, describe their characteristics and identify factors associated with overall mortality in this patient population. Hospitalized COVID-19 patients with Candida spp. isolation were retrospectively assessed and their clinical, laboratory and microbiological characteristics were assessed and evaluated. In total, 69 patients with COVID-19 had a positive culture for Candida spp., representing a rate of 4.5% among all hospitalized COVID-19 patients. Their median age was 78 years (IQR 67–85 years) and 44.9% were male. Hospitalized patients with COVID-19 and Candida spp. isolation who died were older, were more likely to have a diagnosis of dementia, and had higher Charlson comorbidity index, higher Candida score and higher 4C score. Candida score was identified with a multivariate logistic regression analysis model to be independently associated with mortality. The most commonly identified Candida species was C. albicans, followed by C. tropicalis and C. glabrata and the most common source was the urine, even though in most cases the positive culture was not associated with a true infection. Thus, Candida score may be used in COVID-19 patients with isolation of Candida spp. from different body specimens for mortality risk stratification. Full article
9 pages, 719 KiB  
Article
The Diagnostic Relevance of β-D-Glucan for Candidemia within Internal Medicine Wards
by Silvia Corcione, Luisa Chasseur, Tommaso Lupia, Nour Shbaklo, Silvia Scabini, Claudia Filippini, Simone Mornese Pinna, Stefania Morra di Celle, Rossana Cavallo and Francesco Giuseppe De Rosa
Diagnostics 2022, 12(9), 2124; https://doi.org/10.3390/diagnostics12092124 - 1 Sep 2022
Cited by 2 | Viewed by 1266
Abstract
Candidemia diagnosis is based on the combination of clinical, microbiological and laboratory data. We aimed to evaluate performances and accuracy of (1,3)-β-D-glucan (BDG) at various cut-offs in internal medicine patients. An observational retrospective–prospective study was performed. Patients with at least two determinations of [...] Read more.
Candidemia diagnosis is based on the combination of clinical, microbiological and laboratory data. We aimed to evaluate performances and accuracy of (1,3)-β-D-glucan (BDG) at various cut-offs in internal medicine patients. An observational retrospective–prospective study was performed. Patients with at least two determinations of BDG and paired, associated blood cultures within ±48 h were considered. A total of 140 patients were included: 26 with Candida spp. blood-stream infections (BSI) and 114 without candidemia. Patients with candidemia were older and had higher BDG values, need of parenteral nutrition, higher colonization by Candida in more than one site, presence of percutaneous gastrostomy and higher Candida or Charlson scores. BDG maintained the best compromise between sensitivity, specificity and optimal negative predictive value was 150 pg/mL. BDG values at cut-off of 150 pg/mL increase the strength of association between BDG and development of candidemia (Odds Ratio—OR 5.58; CI 2.48–12.53 vs. OR 1.06; CI 1.003–1.008). Analyzing BDG > 150 pg/mL along with Candida score > 2 and Charlson score > 4, the strength of the association amongst BDG, clinical scores and development of candidemia is increased. The overall clinical evaluation with the help of scores that consider BDG values > 150 pg/mL, Candida score > 2 and Charlson score > 4 in combination seems to predict better the need of antifungal empiric treatment. Full article
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Review

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20 pages, 320 KiB  
Review
Fungal Periprosthetic Hip Joint Infections
by Christos Koutserimpas, Symeon Naoum, Vasileios Giovanoulis, Konstantinos Raptis, Kalliopi Alpantaki, Konstantinos Dretakis, Georgia Vrioni and George Samonis
Diagnostics 2022, 12(10), 2341; https://doi.org/10.3390/diagnostics12102341 - 27 Sep 2022
Cited by 5 | Viewed by 1979
Abstract
Introduction: Fungal hip prosthetic joint infections (PJIs) are rare but severe infections. Their incidence has increased in the last decades due to the aging population, as well as due to the increased number of immunosuppressed hosts. The present review of all published fungal [...] Read more.
Introduction: Fungal hip prosthetic joint infections (PJIs) are rare but severe infections. Their incidence has increased in the last decades due to the aging population, as well as due to the increased number of immunosuppressed hosts. The present review of all published fungal PJIs in hip arthroplasties aims to present as much data as possible for both medical and surgical treatment options, so that the best applicable management may be concluded. Methods: A meticulous review of all published fungal hip PJIs was conducted. Information regarding demographics, causative fungus, antifungal treatment (AFT), surgical management as well as the infection outcome was recorded. Results: A total of 89 patients suffering fungal hip PJI were identified. The patients’ mean age was 66.9 years. The mean time from initial arthroplasty to onset of symptoms was 69.3 months, while 40.4% of the patients were immunocompromised. The most common imaging method indicating diagnosis was plain X-ray or CT scan (20.2%), while definite diagnosis had become possible through cultures in most cases (98.9%), and/or histology (44.9%). The most frequently isolated fungus was C. albicans (49.4%), followed by C. parapsilosis (18%) and C. glabrata (12.4%), while bacterial co-infection was present in 32 cases (36%). Two-stage revision arthroplasty (TSRA) was the most commonly performed procedure (52.8%), with mean time between the two stages = 7.9 months. Regarding antifungal treatment (AFT), fluconazole was the preferred agent (62.9%), followed by amphotericin B (36%), while the mean duration of AFT was 5.1 months. Outcome was successful in 68 cases (76.4%). Conclusions: Both diagnosis and management of fungal PJIs in patients having undergone total hip arthroplasty are quite demanding. A multidisciplinary approach is of utmost importance, since the combination of AFT and TSRA appears to be the proper treatment method. Full article

Other

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11 pages, 2487 KiB  
Case Report
Prosthetic Knee Joint Infection Due to Candida lusitaniae: A Diagnostic and Therapeutic Odyssey: A Case Study
by Vasileios Giovanoulis, Angelo V. Vasiliadis, Christos Koutserimpas, George Samonis, Cécile Batailler, Tristan Ferry and Sébastien Lustig
Diagnostics 2022, 12(11), 2640; https://doi.org/10.3390/diagnostics12112640 - 31 Oct 2022
Cited by 2 | Viewed by 1548
Abstract
Prosthetic joint infections (PJIs) caused by fungi, although relatively rare, represent a major surgery-related complication. An extremely rare fungal PJI, following revised total knee replacement (TKR) caused by Candida lusitaniae, is reported, and a meticulous review of similar cases is provided. A [...] Read more.
Prosthetic joint infections (PJIs) caused by fungi, although relatively rare, represent a major surgery-related complication. An extremely rare fungal PJI, following revised total knee replacement (TKR) caused by Candida lusitaniae, is reported, and a meticulous review of similar cases is provided. A 74-year-old female, who underwent primary total knee arthroplasty 10 years ago and a revision surgery three weeks ago, presented with signs and symptoms of PJI. C. lusitaniae was eventually isolated from the periprosthetic tissue using the MALDI-TOF VitekMS–bioMérieux technique. Multiple strategies for managing this fungal PJI were performed, and finally, the patient was treated successfully with an intramedullary arthrodesis system and proper antifungal treatment, including fluconazole. A multidisciplinary approach is essential for the diagnosis and treatment of such severe infections. In persistent cases and in cases where revision surgery is extremely difficult to perform, arthrodesis seems to be an effective solution for the elimination of the infection. The efficacy of the therapeutic management of fungal PJIs remains unclear. Therefore, more research should be reported, focusing on proper treatment so that the optimal strategy in treating these severe infections may be established. Full article
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16 pages, 899 KiB  
Case Report
Fungal Prosthetic Joint Infection in Revised Knee Arthroplasty: An Orthopaedic Surgeon’s Nightmare
by Christos Koutserimpas, Symeon Naoum, Kalliopi Alpantaki, Konstantinos Raptis, Konstantinos Dretakis, Georgia Vrioni and George Samonis
Diagnostics 2022, 12(7), 1606; https://doi.org/10.3390/diagnostics12071606 - 30 Jun 2022
Cited by 3 | Viewed by 2183
Abstract
Fungal prosthetic joint infections (PJIs), despite the fact that they are rare, represent a devastating complication. Such infections in revised knee arthroplasties pose a unique surgical and medical challenge. A rare case of Candida parapsilosis PJI in revised knee arthroplasty is reported. Furthermore, [...] Read more.
Fungal prosthetic joint infections (PJIs), despite the fact that they are rare, represent a devastating complication. Such infections in revised knee arthroplasties pose a unique surgical and medical challenge. A rare case of Candida parapsilosis PJI in revised knee arthroplasty is reported. Furthermore, a thorough review of all published fungal PJIs cases in revised knee arthroplasties is provided. A 72-year-old female with total knee replacement surgery due to osteoarthritis 10 years ago, followed by two revision surgeries six and two years ago due to aseptic loosening, presented with signs and symptoms of septic loosening of the knee components. Resection arthroplasty and cement-spacer placement was performed and periprosthetic tissue cultures yielded Candida parapsilosis. The patient was commenced on proper antifungal treatment (AFT) for six months and then the second stage of the revision surgery was performed successfully. From 2000 to 2022, a total of 46 patients with median age 69 years [interquartile range (IQR = 10)], suffering fungal PJI occurring in revised knee arthroplasty have been reported. The median time from initial arthroplasty to symptoms’ onset was 12 months (IQR = 14). Cultures of local material (52.2%) and histology (6.5%) were the reported diagnostic method, while Candida species were the most commonly isolated fungi. Regarding surgical management, two-stage revision arthroplasty (TSRA) was performed in most cases (54.3%), with median time-interval of six months (IQR = 6) between the two stages. Regarding AFT, fluconazole was the preferred antifungal compound (78.3%), followed by voriconazole and amphotericin B (19.6% each). The median duration of AFT was five months (IQR = 4.5). Infection’s outcome was successful in 38 cases (82.6%). Fungal PJIs, especially in revised knee arthroplasties, are devastating complications. A combination of AFT and TSRA seems to be the treatment of choice. TSRA in these cases poses a special challenge, since major bone defects may be present. Therapeutic procedures remain unclear, thus additional research is needed. Full article
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