Diagnosis of Invasive Aspergillosis on ICU

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 (30 June 2023) | Viewed by 10220

Special Issue Editors

Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany
Interests: anesthesiologist; intensive care medicine; emergency medicine; transplantation; infectious diseases; academic teaching
Department of Anesthesiology and Intensive Care Medicine, University Hospital Essen, Hufelandstr. 55, 45147 Essen, Germany
Interests: intensive care medicine; host–pathogen interactions; mycology; immunology; invasive fungal disease
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Special Issue Information

Dear Colleagues,

After a solid organ or stem cell transplantation, immunocompromised patients or those with severe influenza or with sepsis/septic shock are at risk of developing invasive pulmonary aspergillosis (IPA). Invasive aspergillosis in patients with SARS-CoV-2 infections (CAPA: COVID-19-associated pulmonary aspergillosis) is a rare but serious complication of this pandemic disease.  

IPA is associated with a mortality of >60% in critically ill patients.  The diagnosis of IPA is challenging with an infection, and is only provable with a histopathologic examination. The discrimination between infection and colonization with Aspergillus fumigatus remains challenging and is usually performed by combining patient factors, radiographic features and specific testing. This only yields a certain degree of probability rather than a definitive diagnosis. 

The pathomechanisms leading to the development of IPA/CAPA remain poorly understood, but seem to be associated with the functional state of the immune system and function of neutrophil granulocytes in the lungs. 

Advancements in the diagnosis of this serious disease could lead to timely treatment and might potentially improve the still devastating outcome. Understanding the development of IPA and the course of the disease, especially in critically ill patients, could lead to an improved diagnostic accuracy.

This Special Issue aims to publish high-quality original research, including case reports, reviews and short communications, concerning up-to-date rapid fungal diagnostic techniques, biomarkers and future molecular imaging techniques. We welcome translational research, including immunogenetic risk profiling and pathomechanisms which influence the course of IPA.

Dr. Frank Herbstreit
Dr. Simon Dubler
Guest Editors

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Keywords

  • invasive aspergillosis
  • mycologic testing
  • antimycotic therapy
  • immunosuppression
  • monoclonal antibodies
  • lateral-flow technology
  • galactomannan
  • Aspergillus fumigatus
  • invasive pulmonary aspergillosis
  • aspergillosis
  • imaging
  • positron emission tomography
  • immuno PET
  • antifungals
  • echinocandins
  • fluconazole
  • beta-d-glucan
  • viral pneumonia
  • SARS-CoV-2
  • COVID-19
  • ICU

Published Papers (5 papers)

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Research

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8 pages, 1129 KiB  
Article
A Laboratory-Based Study on Multiple Biomarker Testing in the Diagnosis of COVID-19-Associated Pulmonary Aspergillosis (CAPA): Real-Life Data
by Cornelia Lass-Flörl, Miriam Knoll, Wilfried Posch, Michael Joannidis, Timo Mayerhöfer, Robert Breitkopf and Romuald Bellmann
Diagnostics 2023, 13(1), 114; https://doi.org/10.3390/diagnostics13010114 - 30 Dec 2022
Cited by 4 | Viewed by 1772
Abstract
(1) Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns to contribute to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. (2) Methods: Here, we assessed Aspergillus culture-positive [...] Read more.
(1) Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns to contribute to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. (2) Methods: Here, we assessed Aspergillus culture-positive and culture-negative respiratory tract specimens via direct fungal microscopy (gold standard) and compared the results with galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR. (3) Results: 241 respiratory samples from patients suffering from SARS-CoV-2 pneumonia were evaluated. Results showed both diagnostic tools, Aspergillus PCR and GM-EIA, to be positive or negative displaying a sensitivity of 0.90, a specificity of 0.77, a negative predictive value (NPV) of 0.95, and a positive predictive value (PPV) of 0.58 in Aspergillus sp. culture and microscopic-positive specimens. Non-bronchoalveolar lavage (BAL) samples, obtained within a few days from the same patient, showed a high frequency of intermittent positive or negative GM-EIA or Aspergillus PCR results. Positivity of a single biomarker is insufficient for a proper diagnosis. A broad spectrum of Aspergillus species was detected. (4) Conclusions: Our study highlights the challenges of combined biomarker testing as part of diagnosing CAPA. From the results presented, we highly recommend the additional performance of direct microscopy in respiratory specimens to avoid overestimation of fungal infections by applying biomarkers. Full article
(This article belongs to the Special Issue Diagnosis of Invasive Aspergillosis on ICU)
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12 pages, 665 KiB  
Article
Effect of Dexamethasone on the Incidence and Outcome of COVID-19 Associated Pulmonary Aspergillosis (CAPA) in Critically Ill Patients during First- and Second Pandemic Wave—A Single Center Experience
by Simon Dubler, Ömer Can Turan, Karsten Daniel Schmidt, Peter-michael rath, Hedda-Luise Verhasselt, Sandra Maier, Annabell Skarabis, Thorsten Brenner and Frank Herbstreit
Diagnostics 2022, 12(12), 3049; https://doi.org/10.3390/diagnostics12123049 - 05 Dec 2022
Viewed by 1461
Abstract
Superinfections with Aspergillus spp. in patients with Coronavirus disease 2019 (CAPA: COVID-19-associated pulmonary aspergillosis) are increasing. Dexamethasone has shown beneficial effects in critically ill COVID-19 patients. Whether dexamethasone increases the risk of CAPA has not been studied exclusively. Moreover, this retrospective study aimed [...] Read more.
Superinfections with Aspergillus spp. in patients with Coronavirus disease 2019 (CAPA: COVID-19-associated pulmonary aspergillosis) are increasing. Dexamethasone has shown beneficial effects in critically ill COVID-19 patients. Whether dexamethasone increases the risk of CAPA has not been studied exclusively. Moreover, this retrospective study aimed to identify risk factors for a worse outcome in critically ill COVID-19 patients. Data from 231 critically ill COVID-19 patients with or without dexamethasone treatment from March 2020 and March 2021 were retrospectively analysed. Only 4/169 (6.5%) in the DEXA-group and 13/62 (7.7%) in the Non-DEXA group were diagnosed with probable CAPA (p = 0.749). Accordingly, dexamethasone was not identified as a risk factor for CAPA. Moreover, CAPA was not identified as an independent risk factor for death in multivariable analysis (p = 0.361). In contrast, elevated disease severity (as assessed by Sequential Organ Failure Assessment [SOFA]-score) and the need for organ support (kidney replacement therapy and extracorporeal membrane oxygenation [ECMO]) were significantly associated with a worse outcome. Therefore, COVID-19 treatment with dexamethasone did not increase the risk for CAPA. Moreover, adequately treated CAPA did not represent an independent risk factor for mortality. Accordingly, CAPA might reflect patients’ severe disease state instead of directly influencing outcome. Full article
(This article belongs to the Special Issue Diagnosis of Invasive Aspergillosis on ICU)
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Review

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11 pages, 551 KiB  
Review
Microbiological Non-Culture-Based Methods for Diagnosing Invasive Pulmonary Aspergillosis in ICU Patients
by Ulrike Scharmann, Hedda Luise Verhasselt, Lisa Kirchhoff, Dan-Tiberiu Furnica, Joerg Steinmann and Peter-Michael Rath
Diagnostics 2023, 13(16), 2718; https://doi.org/10.3390/diagnostics13162718 - 21 Aug 2023
Viewed by 896
Abstract
The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is crucial since most clinical signs are not specific to invasive fungal infections. To detect an IPA, different criteria should be considered. Next to host factors and radiological signs, microbiological [...] Read more.
The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is crucial since most clinical signs are not specific to invasive fungal infections. To detect an IPA, different criteria should be considered. Next to host factors and radiological signs, microbiological criteria should be fulfilled. For microbiological diagnostics, different methods are available. Next to the conventional culture-based approaches like staining and culture, non-culture-based methods can increase sensitivity and improve time-to-result. Besides fungal biomarkers, like galactomannan and (1→3)-β-D-glucan as nonspecific tools, molecular-based methods can also offer detection of resistance determinants. The detection of novel biomarkers or targets is promising. In this review, we evaluate and discuss the value of non-culture-based microbiological methods (galactomannan, (1→3)-β-D-glucan, Aspergillus PCR, new biomarker/targets) for diagnosing IPA in ICU patients. Full article
(This article belongs to the Special Issue Diagnosis of Invasive Aspergillosis on ICU)
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13 pages, 671 KiB  
Review
Invasive Aspergillosis in the Intensive Care Unit
by Liam Townsend and Ignacio Martin-Loeches
Diagnostics 2022, 12(11), 2712; https://doi.org/10.3390/diagnostics12112712 - 06 Nov 2022
Cited by 8 | Viewed by 2659
Abstract
Invasive pulmonary aspergillosis (IPA) is a serious condition resulting in significant mortality and morbidity among patients in intensive care units (ICUs). There is a growing number of at-risk patients for this condition with the increasing use of immunosuppressive therapies. The diagnosis of IPA [...] Read more.
Invasive pulmonary aspergillosis (IPA) is a serious condition resulting in significant mortality and morbidity among patients in intensive care units (ICUs). There is a growing number of at-risk patients for this condition with the increasing use of immunosuppressive therapies. The diagnosis of IPA can be difficult in ICUs, and relies on integration of clinical, radiological, and microbiological features. In this review, we discuss patient populations at risk for IPA, as well as the diagnostic criteria employed. We review the fungal biomarkers used, as well as the challenges in distinguishing colonization with Aspergillus from invasive disease. We also address the growing concern of multidrug-resistant Aspergillosis and review the new and novel therapeutics which are in development to combat this. Full article
(This article belongs to the Special Issue Diagnosis of Invasive Aspergillosis on ICU)
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Other

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9 pages, 889 KiB  
Perspective
Invasive Pulmonary Aspergillosis: Not Only a Disease Affecting Immunosuppressed Patients
by Rafael Zaragoza, Jordi Sole-Violan, Rachel Cusack, Alejandro Rodriguez, Luis Felipe Reyes and Ignacio Martin-Loeches
Diagnostics 2023, 13(3), 440; https://doi.org/10.3390/diagnostics13030440 - 26 Jan 2023
Viewed by 2692
Abstract
Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20–30 years, however, the type of patients that have been admitted to hospitals [...] Read more.
Fungal infections have become a common threat in Intensive Care Units (ICU). The epidemiology of invasive fungal diseases (IFD) has been extensively studied in patients severely immunosuppressed over the last 20–30 years, however, the type of patients that have been admitted to hospitals in the last decade has made the healthcare system and ICU a different setting with more vulnerable hosts. Patients admitted to an ICU tend to have older age and higher severity of disease. Moreover, the number of patients being treated in ICU are often immunosuppressed as a result of the widespread use of immunomodulatory agents, such as corticosteroids, chemotherapy, and biological agents. The development of Invasive Pulmonary aspergillosis (IPA) reflects a different clinical trajectory to affected patients. The increasing use of corticosteroids would probably explain the higher incidence of IPA especially in critically ill patients. In refractory septic shock, severe community-acquired pneumonia (SCAP), and acute respiratory distress syndrome (ARDS), the use of corticosteroids has re-emerged in order to decrease unacceptably high mortality rates associated with these clinical conditions. It is also pertinent to note that different reports have used different diagnosis criteria, and this might explain the different incidence rates. Another layer of complexity to better understand current IPA data is related to more aggressive acquisition of samples through invasive respiratory examinations. Full article
(This article belongs to the Special Issue Diagnosis of Invasive Aspergillosis on ICU)
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