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Invasive Fungal Infections 2021
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Invasive Fungal Infections 2021

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 (28 February 2022) | Viewed by 19784

Special Issue Editors

Dr. Livio Pagano

E-Mail Website
Guest Editor
Hematology Department, Catholic University of Sacred Heart, Rome, Italy
Interests: diagnosis and treatment of hematological malignancies; management of bacterial, fungal, and viral infectious complications in neutropenic patients
Prof. Dr. Immaculata Xess

E-Mail Website
Guest Editor
Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India
Interests: medical mycology; invasive fungal infections; drug resistance in fungi

Special Issue Information

Dear Colleagues,

Invasive fungal infections (IFI) are increasing worldwide. They mostly affect two groups of patients—patients with hematological malignancy and patients in the ICU for longer time periods. Opportunistic fungi such as Candida, Aspergillus, Mucor, and non-Aspergillus molds are increasingly found in immunocompromised patients, whereas there are other groups of fungi that primarily affect patients traveling from endemic zones to non-endemic areas. The epidemiology of invasive fungal infections is changing, especially in the current COVID-19 era, meaning resurgences of molds have been reported in some countries. If not treated in a timely manner, IFI can be very fatal. Hence, the aim of this Special Issue is shed light on the current epidemiology, newer diagnostic algorithms that could help to combat diseases, updated assays, and newer drugs that have been recently evaluated and can be habituated for IFI.

Prof. Livio Pagano
Prof. Dr. Immaculata Xess
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

  • changing epidemiology
  • endemic fungi
  • diagnostic algorithm
  • newer diagnostic approach
  • newer drugs

Published Papers (7 papers)

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Editorial

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3 pages, 209 KiB  
Editorial
Invasive Fungal Infections 2021
by Immaculata Xess, Livio Pagano and Yubhisha Dabas
J. Fungi 2022, 8(8), 760; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8080760 - 22 Jul 2022
Cited by 3 | Viewed by 1972
Abstract
Invasive fungal infections (IFIs) represent a significant problem in a large proportion of immunocompromised individuals and critically ill patients [...] Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)

Research

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19 pages, 1323 KiB  
Article
Epidemiology and Antifungal Susceptibility Patterns of Invasive Fungal Infections (IFIs) in India: A Prospective Observational Study
by Yubhisha Dabas, Immaculata Xess, Mragnayani Pandey, Jaweed Ahmed, Janya Sachdev, Azka Iram, Gagandeep Singh, Manoranjan Mahapatra, Rachna Seth, Sameer Bakhshi, Rakesh Kumar, Viveka P. Jyotsna and Sandeep Mathur
J. Fungi 2022, 8(1), 33; https://doi.org/10.3390/jof8010033 - 30 Dec 2021
Cited by 7 | Viewed by 3134
Abstract
The epidemiology of invasive fungal infections (IFI) is ever evolving. The aim of the present study was to analyze the clinical, microbiological, susceptibility, and outcome data of IFI in Indian patients to identify determinants of infection and 30-day mortality. Proven and probable/putative IFI [...] Read more.
The epidemiology of invasive fungal infections (IFI) is ever evolving. The aim of the present study was to analyze the clinical, microbiological, susceptibility, and outcome data of IFI in Indian patients to identify determinants of infection and 30-day mortality. Proven and probable/putative IFI (defined according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group and AspICU criteria) from April 2017 to December 2018 were evaluated in a prospective observational study. All recruited patients were antifungal naïve (n = 3300). There were 253 episodes of IFI (7.6%) with 134 (52.9%) proven and 119 (47%) probable/putative infections. There were four major clusters of infection: invasive candidiasis (IC) (n = 53, 20.9%), cryptococcosis (n = 34, 13.4%), invasive aspergillosis (IA) (n = 103, 40.7%), and mucormycosis (n = 62, 24.5%). The significant risk factors were high particulate efficiency air (HEPA) room admission, ICU admission, prolonged exposure to corticosteroids, diabetes mellitus, chronic liver disease (CLD), acquired immunodeficiency syndrome (AIDS), coronary arterial disease (CAD), trauma, and multiorgan involvement (p < 0.5; odds ratio: >1). The all-cause 30-day mortality was 43.4% (n = 110). It varied by fungal group: 52.8% (28/53) in IC, 58.8% (20/34) in cryptococcosis, 39.8% (41/103) in IA, and 33.9% (21/62) in mucormycosis. HEPA room, ICU admission for IC; HEPA rooms, diabetes mellitus for cryptococcosis; hematological malignancies, chronic kidney disease (CKD), sepsis, galactomannan antigen index value ≥1 for IA and nodules; and ground glass opacities on radiology for mucormycosis were significant predictors of death (odds ratio >1). High minimum inhibitory concentration (MIC) values for azoles were observed in C. albicans, C. parapsilosis, C. glabrata, A. fumigatus, A. flavus, R. arrhizus, R. microsporus, and M. circinelloides. For echinocandin, high MIC values were seen in C. tropicalis, C. guillermondii, C. glabrata, and A. fumigatus. This study highlights the shift in epidemiology and also raises concern of high MICs to azoles among our isolates. It warrants regular surveillance, which can provide the local clinically correlated microbiological data to clinicians and which might aid in guiding patient treatment. Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)
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20 pages, 3522 KiB  
Article
Expression and Purification along with Evaluation of Serological Response and Diagnostic Potential of Recombinant Sap2 Protein from C. parapsilosis for Use in Systemic Candidiasis
by Manisha Shukla, Pankaj Chandley, Harsimran Kaur, Anup K. Ghosh, Shivaprakash M. Rudramurthy and Soma Rohatgi
J. Fungi 2021, 7(12), 999; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7120999 - 23 Nov 2021
Cited by 3 | Viewed by 2091
Abstract
Systemic candidiasis is the fourth most common bloodstream infection in ICU patients worldwide. Although C. albicans is a predominant species causing systemic candidiasis, infections caused by non-albicans Candida (NAC) species are increasingly becoming more prevalent globally along with the emergence of drug resistance. [...] Read more.
Systemic candidiasis is the fourth most common bloodstream infection in ICU patients worldwide. Although C. albicans is a predominant species causing systemic candidiasis, infections caused by non-albicans Candida (NAC) species are increasingly becoming more prevalent globally along with the emergence of drug resistance. The diagnosis of systemic candidiasis is difficult due to the absence of significant clinical symptoms in patients. We investigated the diagnostic potential of recombinant secreted aspartyl proteinase 2 (rSap2) from C. parapsilosis for the detection of Candida infection. The rSap2 protein was successfully cloned, expressed and purified using Ni-NTA chromatography under denaturing conditions using an E. coli-based prokaryotic expression system, and refolded using a multi-step dialysis procedure. Structural analysis by CD and FTIR spectroscopy revealed the refolded protein to be in its near native conformation. Immunogenicity analysis demonstrated the rSap2 protein to be highly immunogenic as evident from significantly high titers of Sap2-specific antibodies in antigen immunized Balb/c mice, compared to sham-immunized controls. The diagnostic potential of rSap2 protein was evaluated using immunoblotting and ELISA assays using proven candidiasis patient serum and controls. Immunoblotting results indicate that reactivity to rSap2 was specific to candidiasis patient sera with no cross reactivity observed in healthy controls. Increased levels of anti-Sap2-specific Ig, IgG and IgM antibodies were observed in candidiasis patients compared to controls and was similar in sensitivity obtained when whole Candida was used as coating antigen. In summary, the rSap2 protein from C. parapsilosis has the potential to be used in the diagnosis of systemic candidiasis, providing a rapid, convenient, accurate and cost-effective strategy. Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)
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17 pages, 364 KiB  
Article
Epidemiology of Candidemia in Kuwait: A Nationwide, Population-Based Study
by Khaled Alobaid, Suhail Ahmad, Mohammad Asadzadeh, Eiman Mokaddas, Noura Al-Sweih, Khalifa Albenwan, Wadha Alfouzan, Inaam Al-Obaid, Ahlam Jeragh, Ebtihal Al-Roomi, Ziauddin Khan, Leena Joseph and Soumya Varghese
J. Fungi 2021, 7(8), 673; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7080673 - 20 Aug 2021
Cited by 12 | Viewed by 2551
Abstract
The Candida species cause a majority of invasive fungal infections. In this article, we describe the nationwide epidemiology of candidemia in Kuwait in 2018. Yeast bloodstream isolates submitted from all major hospitals and identified by phenotypic MALDI-TOF MS and/or by molecular methods were [...] Read more.
The Candida species cause a majority of invasive fungal infections. In this article, we describe the nationwide epidemiology of candidemia in Kuwait in 2018. Yeast bloodstream isolates submitted from all major hospitals and identified by phenotypic MALDI-TOF MS and/or by molecular methods were studied. Susceptibility testing was performed by Etest. Out of 313 bloodstream yeasts, 239 Candida spp. isolates (excluding duplicate isolates) were obtained during 234 candidemic episodes among 223 patients. Mixed-species candidemia and re-infection occurred in 5 and 11 patients, respectively. C. albicans (n = 74), C. parapsilosis (n = 54), C. tropicalis (n = 35), C. auris (n = 33), C. glabrata (n = 32), other Candida spp. (n = 11), and other yeasts (n = 9) caused fungemia. Nearly 50% of patients were in intensive care units. Candida spp. isolates (except C. glabrata) were susceptible to caspofungin and 27% of C. auris were amphotericin B-resistant. Resistance to fluconazole was 100% in C. auris, 17% in C. parapsilosis, 12% in C. glabrata, and 1% in C. albicans. Mortality was 47% for other Candida/yeast infections. Nationwide candidemia incidence in 2018 was 5.29 cases/100,000 inhabitants. Changes in species spectrum, increasing fluconazole resistance in C. parapsilosis, and the emergence of C. auris as a major pathogen in Kuwait are noteworthy findings. The data could be of help in informing decisions regarding planning, in the allocation of resources, and in antimicrobial stewardship. Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)
12 pages, 1438 KiB  
Article
Dynamics and Predictors of Mortality Due to Candidemia Caused by Different Candida Species: Comparison of Intensive Care Unit-Associated Candidemia (ICUAC) and Non-ICUAC
by Yong Jun Kwon, Eun Jeong Won, Seok Hoon Jeong, Kyeong Seob Shin, Jeong Hwan Shin, Young Ree Kim, Hyun Soo Kim, Young Ah Kim, Young Uh, Taek Soo Kim, Jae Hyeon Park, Jaehyeon Lee, Min Ji Choi, Seung A. Byun, Soo Hyun Kim and Jong Hee Shin
J. Fungi 2021, 7(8), 597; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7080597 - 24 Jul 2021
Cited by 9 | Viewed by 2789
Abstract
We investigated mortality and predictors of mortality due to intensive care unit-associated candidemia (ICUAC) versus non-ICUAC by Candida species. This study included all candidemia cases in 11 hospitals from 2017 to 2018 in South Korea. The all-cause mortality rates in all 370 patients [...] Read more.
We investigated mortality and predictors of mortality due to intensive care unit-associated candidemia (ICUAC) versus non-ICUAC by Candida species. This study included all candidemia cases in 11 hospitals from 2017 to 2018 in South Korea. The all-cause mortality rates in all 370 patients with ICUAC were approximately twofold higher than those in all 437 patients with non-ICUAC at 7 days (2.3-fold, 31.1%/13.3%), 30 days (1.9-fold, 49.5%/25.4%), and 90 days (1.9-fold, 57.8%/30.9%). Significant species-specific associations with 7- and 30-day ICUAC-associated mortality were not observed. Multivariate analysis revealed that ICU admission was an independent predictor of Candida glabrata (OR, 2.07–2.48) and Candida parapsilosis-associated mortality (OR, 6.06–11.54). Fluconazole resistance was a predictor of C. glabrata-associated mortality (OR, 2.80–5.14). Lack (less than 3 days) of antifungal therapy was the strongest predictor of 7-day mortality due to ICUAC caused by Candida albicans (OR, 18.33), Candida tropicalis (OR, 10.52), and C. glabrata (OR, 21.30) compared with 30- and 90-day mortality (OR, 2.72–6.90). C. glabrata ICUAC had a stronger association with lack of antifungal therapy (55.2%) than ICUAC caused by other species (30.6–36.7%, all p < 0.05). Most predictors of mortality associated with ICUAC were distinct from those associated with non-ICUAC and were mediated by Candida species. Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)
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19 pages, 3646 KiB  
Article
Favorable Effects of Voriconazole Trough Concentrations Exceeding 1 μg/mL on Treatment Success and All-Cause Mortality: A Systematic Review and Meta-Analysis
by Yuki Hanai, Yukihiro Hamada, Toshimi Kimura, Kazuaki Matsumoto, Yoshiko Takahashi, Satoshi Fujii, Kenji Nishizawa, Yoshitsugu Miyazaki and Yoshio Takesue
J. Fungi 2021, 7(4), 306; https://0-doi-org.brum.beds.ac.uk/10.3390/jof7040306 - 16 Apr 2021
Cited by 19 | Viewed by 2871
Abstract
This systematic review and meta-analysis examined the optimal trough concentration of voriconazole for adult patients with invasive fungal infections. We used stepwise cutoffs of 0.5–2.0 μg/mL for efficacy and 3.0–6.0 μg/mL for safety. Studies were included if they reported the rates of all-cause [...] Read more.
This systematic review and meta-analysis examined the optimal trough concentration of voriconazole for adult patients with invasive fungal infections. We used stepwise cutoffs of 0.5–2.0 μg/mL for efficacy and 3.0–6.0 μg/mL for safety. Studies were included if they reported the rates of all-cause mortality and/or treatment success, hepatotoxicity, and nephrotoxicity according to the trough concentration. Twenty-five studies involving 2554 patients were included. The probability of mortality was significantly decreased using a cutoff of ≥1.0 μg/mL (odds ratio (OR) = 0.34, 95% confidence interval (CI) = 0.15–0.80). Cutoffs of 0.5 (OR = 3.48, 95% CI = 1.45–8.34) and 1.0 μg/mL (OR = 3.35, 95% CI = 1.52–7.38) also increased the treatment success rate. Concerning safety, significantly higher risks of hepatotoxicity and neurotoxicity were demonstrated at higher concentrations for all cutoffs, and the highest ORs were recorded at 4.0 μg/mL (OR = 7.39, 95% CI = 3.81–14.36; OR = 5.76, 95% CI 3.14–10.57, respectively). Although further high-quality trials are needed, our findings suggest that the proper trough concentration for increasing clinical success while minimizing toxicity is 1.0–4.0 μg/mL for adult patients receiving voriconazole therapy. Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)
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Other

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9 pages, 418 KiB  
Case Report
Fatal Breakthrough Candidemia in an Immunocompromised Patient in Kuwait Due to Candida auris Exhibiting Reduced Susceptibility to Echinocandins and Carrying a Novel Mutation in Hotspot-1 of FKS1
by Inaam Al-Obaid, Mohammad Asadzadeh, Suhail Ahmad, Khaled Alobaid, Wadha Alfouzan, Ritu Bafna, Maha Emara and Leena Joseph
J. Fungi 2022, 8(3), 267; https://0-doi-org.brum.beds.ac.uk/10.3390/jof8030267 - 06 Mar 2022
Cited by 17 | Viewed by 2608
Abstract
Candida auris is an emerging yeast pathogen that has recently caused major outbreaks in healthcare facilities worldwide. Clinical C. auris isolates are usually resistant to fluconazole and readily develop resistance to echinocandins and amphotericin B (AMB) during treatment. We describe here an interesting [...] Read more.
Candida auris is an emerging yeast pathogen that has recently caused major outbreaks in healthcare facilities worldwide. Clinical C. auris isolates are usually resistant to fluconazole and readily develop resistance to echinocandins and amphotericin B (AMB) during treatment. We describe here an interesting case of C. auris infection in an immunocompromised patient who had previously received AMB and caspofungin treatment. Subsequently, C. auris was isolated from tracheal (tracheostomy) secretions and twice from urine and all three isolates were susceptible to AMB and micafungin. The patient received a combination therapy with AMB and caspofungin. Although the C. auris was cleared from the urine, the patient subsequently developed breakthrough candidemia and the bloodstream isolate exhibited a reduced susceptibility to micafungin and also showed the presence of a novel (S639T) mutation in hotspot-1 of FKS1. Interestingly, C. auris from the tracheal (tracheostomy) secretions recovered one and four days later exhibited a reduced susceptibility to micafungin and S639Y and S639T mutations in hotspot-1 of FKS1, respectively. Although the treatment was changed to voriconazole, the patient expired. Our case highlights a novel FKS1 mutation and the problems clinicians are facing to treat invasive C. auris infections due to inherent or developing resistance to multiple antifungal drugs and limited antifungal armamentarium. Full article
(This article belongs to the Special Issue Invasive Fungal Infections 2021)
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