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Antibiotics
Special Issues
Diagnosis and Treatment of Fungal Infections
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Diagnosis and Treatment of Fungal Infections

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiotic Therapy in Infectious Diseases".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 25097

Special Issue Editors

Dr. Dominik Łagowski

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Guest Editor
Sub-department of Veterinary Microbiology, Department of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland
Interests: dermatophytes; antifungal resistance mechanisms; veterinary mycology; antifungals; drug susceptibility of fungi; pathogenesis of fungal infections
Dr. Sebastian Gnat

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Guest Editor
Department of Veterinary Microbiology, Institute of Preclinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Life Sciences, 20-033 Lublin, Poland
Interests: antifungals; antifungals resistance mechanisms; fungal zoonoses; natural antimycotics; asymptomatic carriers in animals; public health
Special Issues, Collections and Topics in MDPI journals
Dr. Mariusz Dyląg

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Guest Editor
Department of Mycology and Genetics, Faculty of Biological Sciences, University of Wroclaw, 51-148 Wroclaw, Poland
Interests: mycology; fungal pathogens; virulence factors; conventional and molecular identification of fungi; Cryptococcus; Malassezia; etiological factors of dermatomycoses; antifungals; mechanisms of resistance; evolution of determinants of fungal pathogenicity
Dr. Aneta Nowakiewicz

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Guest Editor
Department of Veterinary Microbiology, Faculty of Veterinary Medicine, University of Life Sciences, 20-033 Lublin, Poland
Interests: antimicrobial resistance mechanisms; wildlife zoonoses; indicator bacteria; livestock impact on environment; antimicrobial resistance circulation; public health
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleague,

Paradoxically, despite the progress in medicine, the prevalence of fungal infections is increasing each year, and the therapeutic measures available at the beginning of the third millennium are still highly limited. The first concerns about the increasing prevalence of fungal infections emerged in the first decades of the 20th century, ascribed to various environmental factors and anthropopressure. Consequently, the first therapeutic attempts to treat these infections were undertaken.

Although pathogenic fungi are one of the oldest groups of microorganisms, they were not part of any stable taxonomic system for a long time. Given the enormous number of taxonomic differences between related fungal pathogens and the importance of species-level identification, the gold standard to use for routine identification of dermatophytes has become the subject of an ongoing debate, and microbiologists' opinions are still inconsistent. Hence, currently reliable establishment of the boundaries of fungal species and, thus, accurate species identification require a multidirectional approach, as it is easy to make a mistake in diagnosis. The importance of correct identification of the etiological factor of mycosis is most clearly appreciated when treatment fails. However, the inefficiency of therapy applied in the course of fungal infections may have many more causes than only the wrong diagnosis.

Historically, the first antifungal drugs were limited to nonspecific agents, e.g., iodide, mercury, benzoic and salicylic acids, phenol derivatives, undecylenic acid, methyl violet, sulfonamide derivatives, and other factors, with usually harmful effects on human health such as preparations based on bromine, potassium permanganate, and turpentine oil mixed with olive oil. The interest in clinical antifungal therapy has gradually increased since then, although the rate of development of antifungal drugs has been very slow to date. Despite the availability of at least a few classes of antifungal drugs intended for clinical use, they have a limited spectrum of accessible cellular targets. Nowadays, the search for synthetic and natural chemical compounds that may constitute new therapeutic options due to their antifungal activity against pathogenic fungi fits in the concept of finding the “holy grail” in antifungal therapy. Another problem resulting from the widespread use of antifungal drugs, and related to the overlapping mechanisms of action and identical cellular targets, is the emergence of multidrug resistance (MDR) phenotypes in an increasing number of pathogenic fungi. Hence, in vitro tests of antifungal drugs and a description of the mechanisms contributing to this emerging resistance are the present tasks for the mycologist milieu.

In the context of the increase in new literature focused on the diagnostics and therapy of fungal infections, this Special Issue is being launched. The aim is to provide a single source to showcase the highlights of new and up-to-date research from all areas of clinical and veterinary diagnostics and therapy for fungal infectious disease.

Dr. Dominik Łagowski
Dr. Sebastian Gnat
Dr. Mariusz Dyląg
Dr. Aneta Nowakiewicz
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. Antibiotics 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 2900 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

  • antifungal therapy
  • fungi
  • qPCR
  • dermatophytes
  • drug susceptibility
  • Cryptococcus
  • Malassezia
  • mechanisms of resistance
  • MALDI/TOF
  • natural antimycotics
  • molds
  • fungal infection
  • antigen detection
  • molecular detection
  • invasive fungal infections

Published Papers (7 papers)

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Research

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13 pages, 2701 KiB  
Article
Laboratory Diagnosis and In Vitro Antifungal Susceptibility of Trichophyton quinckeanum from Human Zoonoses and Cats
by Dominik Łagowski, Sebastian Gnat, Mariusz Dyląg and Aneta Nowakiewicz
Antibiotics 2022, 11(6), 739; https://doi.org/10.3390/antibiotics11060739 - 30 May 2022
Cited by 2 | Viewed by 1726
Abstract
The “One Health” concept increasingly demonstrates the global spread of pathogenic (also eukaryotic) microorganisms and their zoonotic potential. Dermatophytes can cause superficial mycoses in humans and animals. Furthermore, the number of transmissions from asymptomatic carriers to humans has been on the rise over [...] Read more.
The “One Health” concept increasingly demonstrates the global spread of pathogenic (also eukaryotic) microorganisms and their zoonotic potential. Dermatophytes can cause superficial mycoses in humans and animals. Furthermore, the number of transmissions from asymptomatic carriers to humans has been on the rise over the last few years. This study was focused on the detailed characterisation of clinical isolates of Trichophyton quinckeanum with epidemiological analyses and characterisation of their in vitro antifungal susceptibility patterns. The isolated dermatophytes were identified with a combination of conventional and molecular methods. In turn, their susceptibility in vitro was tested according to the Clinical and Laboratory Standards Institute (CLSI) M38 ed.3 protocol. A total of 36 strains were isolated, with 21 cases of T. quinckeanum zoonoses resulting from direct contact with symptomatic cats (58.3%). The other 15 strains (41.7%) were isolated simultaneously from healthy cats and their owners. All strains showed high susceptibility to allylamine, pyridinone, and phenyl morpholine derivatives but were resistant to fluconazole and ketoconazole. In conclusion, our study shows the frequency of zoonoses contracted from asymptomatic cats. Moreover, the antifungal susceptibility profiles indicate the serious risk posed to animal owners by resistant strains of T. quinckeanum, which are often responsible for recalcitrant-to-treatment cases. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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8 pages, 636 KiB  
Article
Combination of C-Reactive Protein and Procalcitonin in Distinguishing Fungal from Bacterial Infections Early in Immunocompromised Children
by Yingli Liu, Xiaoli Zhang, Tianfang Yue, Yanlai Tang, Zhiyong Ke, Yu Li, Xuequn Luo and Libin Huang
Antibiotics 2022, 11(6), 730; https://doi.org/10.3390/antibiotics11060730 - 29 May 2022
Cited by 2 | Viewed by 2221
Abstract
Invasive fungal infection (IFI) is life-threatening in children with cancer and hematology disorders, especially when diagnosis and treatment are delayed. Conventional β-D-glucan and galactomannan tests have poor positive predictive values in the diagnosis of IFI in children with cancer. This study aims to [...] Read more.
Invasive fungal infection (IFI) is life-threatening in children with cancer and hematology disorders, especially when diagnosis and treatment are delayed. Conventional β-D-glucan and galactomannan tests have poor positive predictive values in the diagnosis of IFI in children with cancer. This study aims to access the diagnostic performance of C-reactive protein (CRP) and procalcitonin (PCT) in differentiating IFI from bacterial bloodstream infections in children with malignant and hematology disorders. CRP and PCT levels were measured in samples taken from patients between 12 and 24 h after fever onset, of which 24 and 102 were in the IFI and bacterial groups, respectively. We found that the CRP levels were much higher in the IFI group than the bacterial group (100.57 versus 40.04 mg/L, median, p < 0.001), while the PCT levels remained significantly lower (0.45 versus 1.29 μg/L, median, p = 0.007). Both CRP and PCT showed significant diagnostic utilities with an area under the curve (AUC) of 0.780 (95% CI, 0.664–0.896, p < 0.001) and 0.731 (95% CI, 0.634–0.828, p < 0.001) when using the cut-off values of 94.93 mg/L and 2.00 μg/L, respectively. However, the combined biomarker of CRP and PCT yielded a better diagnostic performance with an AUC of 0.934 (95% confidential interval (CI), 0.881–0.987, p < 0.001), which was significantly higher than that of CRP or PCT (both p < 0.001), with a sensitivity of 87.5% and a specificity of 87.3%. Our study demonstrates high levels of CRP combined with low PCT could differentiate IFI from bacterial bloodstream infections in immunocompromised children. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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Review

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16 pages, 1691 KiB  
Review
Invasive Candidiasis: Update and Current Challenges in the Management of This Mycosis in South America
by Fernando Oscar Riera, Juan Pablo Caeiro, Sofia Carla Angiolini, Cecilia Vigezzi, Emilse Rodriguez, Paula Alejandra Icely and Claudia Elena Sotomayor
Antibiotics 2022, 11(7), 877; https://doi.org/10.3390/antibiotics11070877 - 30 Jun 2022
Cited by 23 | Viewed by 6938
Abstract
Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The [...] Read more.
Invasive candidiasis encompassing Candida bloodstream infections and deep-seated candidiasis can become a persistent health problem. These infections are caused by Candida species and have high morbidity and mortality rates. Species distribution, access to diagnosis, treatment and mortality are different around the world. The mortality rate is high in South America (30–70%), and Candida albicans is the most prevalent species in this region. However, a global epidemiological shift to non-albicans species has been observed. In this group, C. parapsilosis is the species most frequently detected, followed by C. tropicalis, and at a slower rate, C. glabrata, which has also increased, in addition to the emerging C. auris, resistance to several drugs. This article summarizes relevant aspects of candidemia pathogenesis, such as the mechanisms of fungal invasion, immune response, and the impact of genetic defects that increase host susceptibility to developing the infection. We also discuss relevant aspects of treatment and future challenges in South America. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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8 pages, 716 KiB  
Review
COVID-19 and Fungal Diseases
by Kyoung-Ho Oh and Seung-Hoon Lee
Antibiotics 2022, 11(6), 803; https://doi.org/10.3390/antibiotics11060803 - 15 Jun 2022
Cited by 6 | Viewed by 2710
Abstract
Coronavirus Disease-2019 (COVID-19) can cause secondary bacterial and fungal infections by affecting the expression of pro-inflammatory markers, such as tumor necrosis alpha and certain cytokines, as well as the numbers of CD4 and CD8 cells. In particular, in the head and [...] Read more.
Coronavirus Disease-2019 (COVID-19) can cause secondary bacterial and fungal infections by affecting the expression of pro-inflammatory markers, such as tumor necrosis alpha and certain cytokines, as well as the numbers of CD4 and CD8 cells. In particular, in the head and neck, various fungal species are naturally present, making it the main route of secondary infection. It is difficult to clearly distinguish whether secondary infection is caused by COVID-19 directly or indirectly as a result of the immunocompromised state induced by drugs used to treat the disease. However, the risk of fungal infection is high in patients with severe COVID-19, and lymphopenia is observed in most patients with the disease. Patients with COVID-19 who are immunosuppressed or have other pre-existing comorbidities are at a significantly higher risk of acquiring invasive fungal infections. In order to reduce morbidity and mortality in these patients, early diagnosis is required, and treatment with systemic antifungal drugs or surgical necrotic tissue resection is essential. Therefore, this review aimed to examine the risk of fungal infection in the head and neck of patients with COVID-19 and provide information that could reduce the risk of mortality. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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19 pages, 718 KiB  
Review
Diagnosis and Treatment of Invasive Candidiasis
by Natalia Barantsevich and Elena Barantsevich
Antibiotics 2022, 11(6), 718; https://doi.org/10.3390/antibiotics11060718 - 26 May 2022
Cited by 43 | Viewed by 6318
Abstract
Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The [...] Read more.
Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The most frequently diagnosed invasive infection is candidemia. About 50% of candidemia cases result in deep-seated infection due to hematogenous spread. The sensitivity of blood cultures in autopsy-proven invasive candidiasis ranges from 21% to 71%. Non-cultural methods (beta-D-glucan, T2Candida assays), especially beta-D-glucan in combination with procalcitonin, appear promising in the exclusion of invasive candidiasis with high sensitivity (98%) and negative predictive value (95%). There is currently a clear deficiency in approved sensitive and precise diagnostic techniques. Omics technologies seem promising, though require further development and study. Therapeutic options for invasive candidiasis are generally limited to four classes of systemic antifungals (polyenes, antimetabolite 5-fluorocytosine, azoles, echinocandins) with the two latter being highly effective and well-tolerated and hence the most widely used. Principles and methods of treatment are discussed in this review. The emergence of pan-drug-resistant C. auris strains indicates an insufficient choice of available medications. Further surveillance, alongside the development of diagnostic and therapeutic methods, is essential. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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Other

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10 pages, 600 KiB  
Case Report
Therapeutic Drug Monitoring of Amphotericin-B in Plasma and Peritoneal Fluid of Pediatric Patients after Liver Transplantation: A Case Series
by Francesca Tortora, Luigi Dei Giudici, Raffaele Simeoli, Fabrizio Chiusolo, Sara Cairoli, Paola Bernaschi, Roberto Bianchi, Sergio Giuseppe Picardo, Carlo Dionisi Vici and Bianca Maria Goffredo
Antibiotics 2022, 11(5), 640; https://doi.org/10.3390/antibiotics11050640 - 11 May 2022
Cited by 3 | Viewed by 1906
Abstract
Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim [...] Read more.
Fungal infections represent a serious complication during the post-liver transplantation period. Abdominal infections can occur following pre-existing colonization, surgical procedures, and permanence of abdominal tubes. In our center, liposomal amphotericin-B is used as antifungal prophylaxis in pediatric patients undergoing liver transplantation. The aim of this study is to evaluate peritoneal levels of amphotericin-B following intravenous administration. Six liver recipients received liposomal amphotericin-B. Three of them were treated as prophylaxis; meanwhile, three patients received liposomal amphotericin-B to treat Candida albicans infection. Plasma and peritoneal amphotericin-B levels were measured by LC-MS/MS in two consecutive samplings. Cmin (pre-dose) and Cmax (2 h after the end of infusion) were evaluated as drug exposure parameters for both plasma and peritoneum. Our results showed that peritoneal amphotericin-B levels were significantly lower than plasma and that the correlation coefficient was 0.72 (p = 0.03) between plasma and peritoneal Cmin. Moreover, although peritoneal levels were within the therapeutic range, they never reached the PK/PD target (Cmax/MIC > 4.5). In conclusion, PK exposure parameters could be differently used to analyze amphotericin-B concentrations in plasma and peritoneum. However, liposomal amphotericin-B should be preferred in these patients as prophylactic rather than therapeutic treatment for fungal infections. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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7 pages, 966 KiB  
Case Report
Possible COVID-19-Associated Pulmonary Aspergillosis Due to Aspergillus niger in Greece
by Maria Katsiari, Angeliki Mavroidi, Eleftheria Palla, Konstantina Zourla, Theodoros Alonistiotis, Kyriakos Ntorlis, Charikleia Nikolaou, Georgia Vrioni and Athanasios Tsakris
Antibiotics 2022, 11(3), 300; https://doi.org/10.3390/antibiotics11030300 - 23 Feb 2022
Cited by 3 | Viewed by 2063
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) [...] Read more.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes direct damage to the pulmonary epithelium, enabling Aspergillus invasion. Rapid progression and high mortality of invasive aspergillosis have been reported. In the present study, we report a rare case of possible COVID-19-associated pulmonary aspergillosis (CAPA) caused by A. niger in a Greek patient. Diagnosis was based on ECMM/ISHAM specific criteria and the new algorithm “BM-AspICU” for the invasive pulmonary aspergillosis diagnostic strategy. The fungal isolate was recovered in a non-bronchoalveolar lavage (non-BAL) sample and its identification was performed by standard macroscopic and microscopic morphological studies. MALDI-TOF analysis confirmed the identification of A. niger. In addition, galactomannan antigen and Aspergillus real-time PCR testing were positive in the non-BAL sample, while in serum they proved negative. The A. niger isolate showed an MIC for fluconazole ≥128 μg/mL, for itraconazole and posaconazole 0.25 μg/mL, for voriconazole 0.5 μg/mL, for flucytosine 4 μg/mL, for amphotericin B 1 μg/mL, and for all echinocandins (caspofungin, anidulafungin, micafungin) >8 μg/mL. The patient was initially treated with voriconazole; amphotericin B was subsequently added, when a significant progression of cavitation was demonstrated on chest computed tomography. A. niger was not isolated in subsequent samples and the patient’s unfavorable outcome was attributed to septic shock caused by a pandrug-resistant Acinetobacter baumannii strain. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Fungal Infections)
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