Characterizing Diversity and Antifungal Resistance in Immunocompromised ICU Patients With Respiratory Tract Infections

Overview

Immunocompromised individuals face a heightened risk of life-threatening fungal infections, which arise from a multitude of environmental and commensal fungi. Surveillance data from ICUs worldwide identifies Candida spp. as the dominant foe, responsible for 80% of such infections, earning it the dubious distinction of being the third most prevalent pathogen. While C. albicans holds the dubious crown as the most common Candida offender, recent years have witnessed a concerning trend toward non-Albicans candida, raising concerns about potential antifungal resistance.

For critically ill patients in the ICU, the threat of invasive fungal infections is a hidden danger, particularly in the presence of any of the following opportunistic factors: (A) Pre-existing lung disease: Idiopathic pulmonary fibrosis (IPF) , Chronic obstructive pulmonary disease (COPD), or Sarcoidosis. (B) Patient comorbidities: 1. Immunosuppression: Neutropenia, Corticosteroid therapy, Immunosuppressive medication for inflammatory or autoimmune diseases; T-cell suppressants: Antithymocyte globulin (ATG), Calcineurin inhibitors (e.g., tacrolimus, cyclosporine) or B-cell suppressants: Rituximab, Severe sepsis (immune paralysis): Inherited severe immunodeficiency: Chronic granulomatous disease (CGD), Wiskott-Aldrich syndrome (WAS), and Common variable immunodeficiency (CVID) or Acquired immunodeficiency due to HIV/AIDS. 2. Underlying medical conditions: Liver failure, Diabetes mellitus, or cardiovascular disease. 3. Viral Pneumonia: Influenza-associated pulmonary aspergillosis (IAPA) and Coronavirus disease 2019 (COVID-19) 4. Hematological and solid malignancies. 5. Hematopoietic stem cell transplantation (HSCT). 6. Prior fungal exposure: Aspergillus colonization before or during ICU admission . (C) Environmental factors: Construction work, Geo-climatic factors, Tobacco or cannabis use, Air, food, or spice contamination, Gardening activity or occupation. For diagnosing an invasive fungal infection (IFI), symptoms are unspecific; fever, cough, or chest pain and often missed in patients on corticosteroids, the host criteria including the presence of high-risk factors like neutropenia, malignancies, or immunosuppression, the clinical criteria; specific imaging findings on chest X-ray, high-resolution computed tomography (HRCT) or bronchoscopy indicating pulmonary involvement then finally mycological Criteria: Positive fungal detection in samples (culture, polymerase chain reaction 'PCR', GM). In Non-Hematological Patients, diagnosis often delayed due to atypical symptoms and imaging, potentially leading to airway invasion vs. angioinvasion, differing clinical presentation and tests. Also, Lower GM yield compared to hematological patients. Crucially, this delayed diagnosis contributes to the higher mortality in non-hematological patients. This underscores the urgent need to establish improved diagnostic capabilities for invasive pulmonary aspergillosis using mycological tests in non-hematological individuals. By closely monitoring the prevalence and drug susceptibility patterns of fungal pathogens, leads to acquiring crucial insights into their dynamics and refine the therapeutic approaches accordingly. This data empowers clinicians to make informed decisions regarding antifungal therapy, minimizing unnecessary drug exposure and preserving the effectiveness of the antifungal weapons. Based on the need for more specific studies on diagnosis, prophylaxis, and therapy of critically ill, non-neutropenic, patients, and the significant threats of fungal infections to immunocompromised patients, particularly in ICU settings, understanding the diversity and antifungal resistance of these infections is crucial for optimizing treatment strategies and improving patient outcomes. This study will provide valuable insights into the epidemiology and antifungal resistance of fungal infections in immunocompromised ICU patients, informing the development of more effective prevention and treatment strategies.