Fungal Infections in Modern Critical Care Medicine: Advances in Diagnostic and Treatment

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 (30 September 2023) | Viewed by 9793

Special Issue Editors


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Guest Editor
Medical Mycology Reference Laboratory (MMRL), Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Interests: medical mycology; laboratory diagnosis; epidemiology; public health
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Special Issue Information

Dear Colleagues,

The outstanding development of critical care in recent decades has led to improved patient outcomes and reduced mortality. However, fungal infections still have a significant impact on survival. Multidisciplinary care of the critically ill is an integral part of every modern healthcare system, ensuring infection control and improved outcomes while reducing mortality. Faster and easier access to diagnostics, the early recognition of infection, advanced antifungal therapy, and organized critical care in centers all lead to a reduction in mortality from fungal infections. However, due to fungal resistance, immunocompromised and critically ill patients still present a vulnerable population. Finally, the fast development of technology and continuous ongoing research in the field of critical care mean that clinicians need constant and continued access to medical education. The main goal of this Special Issue is to summarize and collect the newest information on fungal infections and their influence on patient outcomes, especially focusing on critically ill and immunocompromised patients. In this Special Issue, we will explore the diagnostic modalities and therapies for critically ill patients with fungal infections. Specifically, this Special Issue welcomes articles on:

  • Advances and developments in antifungal therapy, strategies, and protocols;
  • Advances and developments in fungal diagnostics;
  • The management of complications caused by fungi;
  • The epidemiology and pathophysiology of fungal infections in critically ill patients;
  • Fungal infections in immunocompromised patients;
  • Fungal infections and transplantation;
  • Fungal infections and patient-related outcomes;
  • Fungal infections and extracorporeal life support;
  • Fungal infections in patients with COVID-19 infection;
  • Training and continuing medical education;
  • The prevention and protection of fungal infections.

We will consider original research articles, systematic review articles, literature or topical review articles, and perspectives and opinions, and we encourage submissions of observational and interventional studies.

Dr. Sasa Rajsic
Prof. Dr. Valentina Arsić Arsenijević
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.

Published Papers (5 papers)

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Research

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17 pages, 1221 KiB  
Article
Invasive Fungal Infections: The Early Killer after Liver Transplantation
by Robert Breitkopf, Benedikt Treml, Zoran Bukumiric, Nicole Innerhofer, Margot Fodor and Sasa Rajsic
J. Fungi 2023, 9(6), 655; https://doi.org/10.3390/jof9060655 - 12 Jun 2023
Cited by 1 | Viewed by 1413
Abstract
Background: Liver transplantation is a standard of care and a life-saving procedure for end-stage liver diseases and certain malignancies. The evidence on predictors and risk factors for poor outcomes is lacking. Therefore, we aimed to identify potential risk factors for mortality and to [...] Read more.
Background: Liver transplantation is a standard of care and a life-saving procedure for end-stage liver diseases and certain malignancies. The evidence on predictors and risk factors for poor outcomes is lacking. Therefore, we aimed to identify potential risk factors for mortality and to report on overall 90-day mortality after orthotopic liver transplantation (OLT), especially focusing on the role of fungal infections. Methods: We retrospectively reviewed medical charts of all patients undergoing OLT at a tertiary university center in Europe. Results: From 299 patients, 214 adult patients who received a first-time OLT were included. The OLT indication was mainly due to tumors (42%, 89/214) and cirrhosis (32%, 68/214), including acute liver failure in 4.7% (10/214) of patients. In total, 8% (17/214) of patients died within the first three months, with a median time to death of 15 (1–80) days. Despite a targeted antimycotic prophylaxis using echinocandins, invasive fungal infections occurred in 12% (26/214) of the patients. In the multivariate analysis, patients with invasive fungal infections had an almost five times higher chance of death (HR 4.6, 95% CI 1.1–18.8; p = 0.032). Conclusions: Short-term mortality after OLT is mainly determined by infectious and procedural complications. Fungal breakthrough infections are becoming a growing concern. Procedural, host, and fungal factors can contribute to a failure of prophylaxis. Finally, invasive fungal infections may be a potentially modifiable risk factor, but the ideal perioperative antimycotic prophylaxis has yet to be determined. Full article
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15 pages, 7726 KiB  
Article
The Novel Monoclonal IgG1-Antibody AB90-E8 as a Diagnostic Tool to Rapidly Distinguish Aspergillus fumigatus from Other Human Pathogenic Aspergillus Species
by Tamara Katharina Kakoschke, Christoph Kleinemeier, Thomas Knösel, Sara Carina Kakoschke and Frank Ebel
J. Fungi 2023, 9(6), 622; https://doi.org/10.3390/jof9060622 - 28 May 2023
Viewed by 1302
Abstract
In most cases, invasive aspergillosis (IA) is caused by A. fumigatus, though infections with other Aspergillus spp. with lower susceptibilities to amphotericin B (AmB) gain ground. A. terreus, for instance, is the second leading cause of IA in humans and of [...] Read more.
In most cases, invasive aspergillosis (IA) is caused by A. fumigatus, though infections with other Aspergillus spp. with lower susceptibilities to amphotericin B (AmB) gain ground. A. terreus, for instance, is the second leading cause of IA in humans and of serious concern because of its high propensity to disseminate and its in vitro and in vivo resistance to AmB. An early differentiation between A. fumigatus and non-A. fumigatus infections could swiftly recognize a potentially ineffective treatment with AmB and lead to the lifesaving change to a more appropriate drug regime in high-risk patients. In this study, we present the characteristics of the monoclonal IgG1-antibody AB90-E8 that specifically recognizes a surface antigen of A. fumigatus and the closely related, but not human pathogenic A. fischeri. We show immunostainings on fresh frozen sections as well as on incipient mycelium picked from agar plates with tweezers or by using the expeditious tape mount technique. All three methods have a time advantage over the common procedures currently used in the routine diagnosis of IA and outline the potential of AB90-E8 as a rapid diagnostic tool. Full article
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17 pages, 1328 KiB  
Article
Invasive Fungal Breakthrough Infections under Targeted Echinocandin Prophylaxis in High-Risk Liver Transplant Recipients
by Robert Breitkopf, Benedikt Treml, Thomas Senoner, Zoran Bukumirić and Sasa Rajsic
J. Fungi 2023, 9(2), 272; https://doi.org/10.3390/jof9020272 - 18 Feb 2023
Cited by 5 | Viewed by 1774
Abstract
Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of [...] Read more.
Invasive fungal infections (IFIs) are frequent and outcome-relevant complications in the early postoperative period after orthotopic liver transplantation (OLT). Recent guidelines recommend targeted antimycotic prophylaxis (TAP) for high-risk liver transplant recipients (HR-LTRs). However, the choice of antimycotic agent is still a subject of discussion. Echinocandins are increasingly being used due to their advantageous safety profile and the increasing number of non-albicans Candida infections. However, the evidence justifying their use remains rather sparse. Recently published data on breakthrough IFI (b-IFI) raise concerns about echinocandin efficacy, especially in the case of intra-abdominal candidiasis (IAC), which is the most common infection site after OLT. In this retrospective study, we analyzed 100 adult HR-LTRs undergoing first-time OLT and receiving echinocandin prophylaxis between 2017 and 2020 in a tertiary university hospital. We found a breakthrough incidence of 16%, having a significant impact on postoperative complications, graft survival, and mortality. The reasons for this may be multifactorial. Among the pathogen-related factors, we identified the breakthrough of Candida parapsilosis in 11% of patients and one case of persistent IFI due to the development of a secondary echinocandin resistance of an IAC caused by Candida glabrata. Consequently, the efficacy of echinocandin prophylaxis in liver transplantation should be questioned. Further studies are necessary to clarify the matter of breakthrough infections under echinocandin prophylaxis. Full article
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17 pages, 2266 KiB  
Article
Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses
by Lucas Perez, Philippe Corne, Grégoire Pasquier, Céline Konecki, Meriem Sadek, Clément Le Bihan, Kada Klouche, Olivier Mathieu, Jacques Reynes and Yoann Cazaubon
J. Fungi 2023, 9(2), 211; https://doi.org/10.3390/jof9020211 - 6 Feb 2023
Cited by 11 | Viewed by 2257
Abstract
Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic [...] Read more.
Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29–2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT. Full article
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16 pages, 3701 KiB  
Systematic Review
Survival Outcome of Empirical Antifungal Therapy and the Value of Early Initiation: A Review of the Last Decade
by Souha S. Kanj, Ali S. Omrani, Hail M. Al-Abdely, Ahmad Subhi, Riad El Fakih, Ibraheem Abosoudah, Hazar Kanj and George Dimopoulos
J. Fungi 2022, 8(11), 1146; https://doi.org/10.3390/jof8111146 - 29 Oct 2022
Cited by 4 | Viewed by 2313
Abstract
Aim: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. Methods: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in [...] Read more.
Aim: This rapid systematic review aimed to collect the evidence published over the last decade on the effect of empirical antifungal therapy and its early initiation on survival rates. Methods: A systematic search was conducted in PubMed, Cochrane, Medline, Scopus, and Embase, in addition to a hand search and experts’ suggestions. Results: Fourteen cohort studies and two randomized clinical trials reporting the survival outcome of empirical antifungal therapy were included in this review. Two studies reported the association between early empirical antifungal therapy (EAFT) and survival rates in a hematological cancer setting, and fourteen studies reported the outcome in patients in intensive care units (ICU). Six studies reported that appropriate EAFT decreases hospital mortality significantly; ten studies could not demonstrate a statistically significant association with mortality rates. Discussion: The inconsistency of the results in the literature can be attributed to the studies’ small sample size and their heterogeneity. Many patients who may potentially benefit from such strategies were excluded from these studies. Conclusion: While EAFT is practiced in many settings, current evidence is conflicting, and high-quality studies are needed to demonstrate the true value of this approach. Meanwhile, insights from experts in the field can help guide clinicians to initiate EAFT when indicated. Full article
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