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

Официальное название

Unveiling the Fungal Frontier: Characterizing Diversity and Antifungal Resistance in Immunocompromised ICU Patients With Respiratory Tract Infections

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Complete blood count
  blood sample
• Диагностический тест C-reactive protein, urea, creatinine, Random blood glucose (RBG), aspartate aminotransferase (AST), alanine aminotransferase (ALT)
  serum sample
• Лучевая терапия CT chest
  Computed tomography of the chest
• Диагностический тест Microscopic examination
  sputum and bronchoalveolar lavage (BAL)
• Диагностический тест culture and sensitivity
  for bacterial and fungal

Первичные конечные точки

• Number of fungal species causing pneumonia in immunocompromised ICU patients [Срок оценки: baseline]

Вторичные конечные точки (2)

• Determine the antifungal susceptibility profiles of the identified fungal isolates. [Срок оценки: baseline]
• Number of associated specific patient factors with the type or antifungal resistance of fungal infections [Срок оценки: baseline]

Критерии участия

Критерии включения

• All adult patients (aged >18 years old) admitted to the Assiut University Hospital's intensive care units with pneumonia and hospitalized patients who developed hospital-acquired or ventilator-associated pneumonia who don't respond to antibiotics for 48 hours or with a CT finding suspected for fungal pneumonia.

Patients included must have at least one of the following conditions as a contributor to immunocompromise:

• Pre-existing lung disease: IPF, COPD, or sarcoidosis.
• Immunosuppression: Neutropenia, on corticosteroids, or immunosuppressive drugs, inherited or acquired immunodeficiency.
• Underlying comorbidities: (Diabetes Mellitus,Chronic kidney disease, Liver cirrhosis)
• Malignancy (Hematological or solid)

Критерии исключения

• Patients refused to contribute to the study.
• Unsatisfactory sample.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

Египет · 1 центр

• Assiut University — Asyut

Публикации

• Sprute R, Nacov JA, Neofytos D, Oliverio M, Prattes J, Reinhold I, Cornely OA, Stemler J. Antifungal prophylaxis and pre-emptive therapy: When and how? Mol Aspects Med. 2023 Aug;92:101190. doi: 10.1016/j.mam.2023.101190. Epub 2023 May 17. PMID 37207579
• Kett DH, Azoulay E, Echeverria PM, Vincent JL; Extended Prevalence of Infection in ICU Study (EPIC II) Group of Investigators. Candida bloodstream infections in intensive care units: analysis of the extended prevalence of infection in intensive care unit study. Crit Care Med. 2011 Apr;39(4):665-70. doi: 10.1097/CCM.0b013e318206c1ca. PMID 21169817
• Bassetti M, Garnacho-Montero J, Calandra T, Kullberg B, Dimopoulos G, Azoulay E, Chakrabarti A, Kett D, Leon C, Ostrosky-Zeichner L, Sanguinetti M, Timsit JF, Richardson MD, Shorr A, Cornely OA. Intensive care medicine research agenda on invasive fungal infection in critically ill patients. Intensive Care Med. 2017 Sep;43(9):1225-1238. doi: 10.1007/s00134-017-4731-2. Epub 2017 Mar 2. PMID 28255613
• Meersseman W, Lagrou K, Maertens J, Van Wijngaerden E. Invasive aspergillosis in the intensive care unit. Clin Infect Dis. 2007 Jul 15;45(2):205-16. doi: 10.1086/518852. Epub 2007 Jun 13. PMID 17578780
• Hage CA, Carmona EM, Evans SE, Limper AH, Ruminjo J, Thomson CC. Summary for Clinicians: Microbiological Laboratory Testing in the Diagnosis of Fungal Infections in Pulmonary and Critical Care Practice. Ann Am Thorac Soc. 2019 Dec;16(12):1473-1477. doi: 10.1513/AnnalsATS.201908-582CME. No abstract available. PMID 31526275

Идентификаторы

NCT: NCT06387667 · FIRTI

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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