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Revista Chilena de Infectologia :... 2018The invasive fungal disease produced by Aspergillus spp., is the infection by filamentous fungi most frequently reported among immunocompromised individuals and... (Review)
Review
The invasive fungal disease produced by Aspergillus spp., is the infection by filamentous fungi most frequently reported among immunocompromised individuals and responsible for a very high mortality in this group of patients. In recent years, important advances have been made both from the diagnostic and therapeutic point of view. At present, a series of risk factors associated with its development have been identified, allowing the categorization of patients in high, intermediate and low risk of invasive aspergillosis (IA); and diagnostic criteria have also been established that consider factors of the host, traditional mycological laboratory, biomarkers such as galactomannan and 1→3-β-d-glucan, together with the better understanding and interpretation of the tomographic images that have allowed to reach a consensus on the diagnostic categories. This added to the incorporation of new antifungals and therapeutic strategies in different scenarios, have allowed decreasing the associated mortality. In this review, are updated the epidemiological aspects, the risk factors, the diagnosis, prevention and prophylaxis as well as the therapeutic confrontation, including strategies for the use of empirical, precocious and directed antifungal therapy, as well as the most relevant aspects of the first-choice and alternative antifungals for the IA management.
Topics: Adult; Antifungal Agents; Aspergillosis; Humans; Risk Factors
PubMed: 30725000
DOI: 10.4067/s0716-10182018000500531 -
Clinical Microbiology Reviews Oct 2009All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of... (Review)
Review
All humans are continuously exposed to inhaled Aspergillus conidia, yet healthy hosts clear the organism without developing disease and without the development of antibody- or cell-mediated acquired immunity to this organism. This suggests that for most healthy humans, innate immunity is sufficient to clear the organism. A failure of these defenses results in a uniquely diverse set of illnesses caused by Aspergillus species, which includes diseases caused by the colonization of the respiratory tract, invasive infection, and hypersensitivity. A key concept in immune responses to Aspergillus species is that the susceptibilities of the host determine the morphological form, antigenic structure, and physical location of the fungus. In this review, we summarize the current literature on the multiple layers of innate defenses against Aspergillus species that dictate the outcome of this host-microbe interaction.
Topics: Animals; Aspergillosis; Aspergillus; Host-Pathogen Interactions; Humans; Immunity, Innate
PubMed: 19822887
DOI: 10.1128/CMR.00014-09 -
F1000Research 2019The introduction of new targeted, biological, and cellular therapies in patients with hematologic malignancies has improved the outcomes of patients but in parallel has... (Review)
Review
The introduction of new targeted, biological, and cellular therapies in patients with hematologic malignancies has improved the outcomes of patients but in parallel has changed the frequency and epidemiology of infections, including invasive aspergillosis (IA). In this article, recent literature on the epidemiology and clinical findings of IA in patients who have lymphoproliferative and myeloproliferative diseases and are undergoing novel targeted treatment with kinase inhibitors, agents targeting cell surface antigens, chimeric antigen receptor-modified T cells, and antibodies to immune checkpoint molecules is reviewed and the clinical impact of IA on the overall management of the underlying disease is discussed. Overall, IA represents a variable and uncommon complication in these populations, but given the increasing eligibility criteria of these novel treatments (particularly in patients with relapsed or refractory hematologic malignancies) and the prolonged periods of therapy, a considerable number of unusual cases of infections can be expected in clinical practice.
Topics: Aspergillosis; Biological Therapy; Cell- and Tissue-Based Therapy; Hematologic Neoplasms; Humans; Molecular Targeted Therapy; Risk Factors
PubMed: 31372213
DOI: 10.12688/f1000research.17836.1 -
MBio Apr 2023Invasive fungal infections are a leading cause of death in immunocompromised patients. Current therapies have several limitations, and innovative antifungal agents are...
Invasive fungal infections are a leading cause of death in immunocompromised patients. Current therapies have several limitations, and innovative antifungal agents are critically needed. Previously, we identified the fungus-specific enzyme sterylglucosidase as essential for pathogenesis and virulence of Cryptococcus neoformans and Aspergillus fumigatus () in murine models of mycoses. Here, we developed sterylglucosidase A (SglA) as a therapeutic target. We identified two selective inhibitors of SglA with distinct chemical scaffolds that bind in the active site of SglA. Both inhibitors induce sterylglucoside accumulation and delay filamentation in and increase survival in a murine model of pulmonary aspergillosis. Structure-activity relationship (SAR) studies identified a more potent derivative that enhances both phenotypes and survival. These findings support sterylglucosidase inhibition as a promising antifungal approach with broad-spectrum potential. Invasive fungal infections are a leading cause of death in immunocompromised patients. Aspergillus fumigatus is a fungus ubiquitously found in the environment that, upon inhalation, causes both acute and chronic illnesses in at-risk individuals. A. fumigatus is recognized as one of the critical fungal pathogens for which a substantive treatment breakthrough is urgently needed. Here, we studied a fungus-specific enzyme, sterylglucosidase A (SglA), as a therapeutic target. We identified selective inhibitors of SglA that induce accumulation of sterylglucosides and delay filamentation in A. fumigatus and increase survival in a murine model of pulmonary aspergillosis. We determined the structure of SglA, predicted the binding poses of these inhibitors through docking analysis, and identified a more efficacious derivative with a limited SAR study. These results open several exciting avenues for the research and development of a new class of antifungal agents targeting sterylglucosidases.
Topics: Animals; Mice; Aspergillus fumigatus; Antifungal Agents; Disease Models, Animal; Aspergillosis; Pulmonary Aspergillosis; Invasive Fungal Infections
PubMed: 36877042
DOI: 10.1128/mbio.00339-23 -
Turkish Journal of Haematology :... May 2023
Topics: Humans; Multiple Myeloma; Aspergillosis; Candidiasis; Invasive Fungal Infections; Antifungal Agents
PubMed: 36890724
DOI: 10.4274/tjh.galenos.2023.2023.0050 -
Journal of the Royal Society of Medicine 1995
Review
Topics: Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Child; Cystic Fibrosis; Humans; Opportunistic Infections
PubMed: 7776328
DOI: No ID Found -
Medical Mycology Journal 2015
Topics: Aspergillosis; Aspergillus fumigatus; Calcium Oxalate; Crystallization; Humans; Lung Diseases, Fungal; Male; Middle Aged; Oxalates; Pneumonectomy
PubMed: 25855022
DOI: 10.3314/mmj.56.J1 -
BMC Infectious Diseases Mar 2021Invasive aspergillosis (IA) is a rare complication in solid organ transplant (SOT) recipients. Although IA has significant implications on graft and patient survival,...
BACKGROUND
Invasive aspergillosis (IA) is a rare complication in solid organ transplant (SOT) recipients. Although IA has significant implications on graft and patient survival, data on diagnosis and management of this infection in SOT recipients are still limited.
METHODS
Discussion of current practices and limitations in the diagnosis, prophylaxis, and treatment of IA and proposal of means of assessing treatment response in SOT recipients.
RESULTS
Liver, lung, heart or kidney transplant recipients have common as well as different risk factors to the development of IA, thus each category needs a separate evaluation. Diagnosis of IA in SOT recipients requires a high degree of awareness, because established diagnostic tools may not provide the same sensitivity and specificity observed in the neutropenic population. IA treatment relies primarily on mold-active triazoles, but potential interactions with immunosuppressants and other concomitant therapies need special attention.
CONCLUSIONS
Criteria to assess response have not been sufficiently evaluated in the SOT population and CT lesion dynamics, and serologic markers may be influenced by the underlying disease and type and severity of immunosuppression. There is a need for well-orchestrated efforts to study IA diagnosis and management in SOT recipients and to develop comprehensive guidelines for this population.
Topics: Aspergillosis; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Invasive Fungal Infections; Organ Transplantation; Patient Outcome Assessment; Practice Guidelines as Topic; Transplant Recipients; Triazoles
PubMed: 33761875
DOI: 10.1186/s12879-021-05958-3 -
Internal Medicine (Tokyo, Japan) Jul 2021
Topics: Aspergillosis; Foreign Bodies; Humans; Pulmonary Aspergillosis
PubMed: 33551407
DOI: 10.2169/internalmedicine.6450-20 -
Clinical Microbiology and Infection :... Jun 2005Acute invasive pulmonary aspergillosis occurs predominantly in immunocompromised hosts, with increasing numbers of cases of invasive aspergillosis among patients with... (Review)
Review
Acute invasive pulmonary aspergillosis occurs predominantly in immunocompromised hosts, with increasing numbers of cases of invasive aspergillosis among patients with chronic obstructive pulmonary disease (COPD) being reported. Among 13 cases of invasive aspergillosis diagnosed in COPD patients admitted to the intensive care unit with acute respiratory distress, the only risk factor for invasive fungal infection was corticosteroid treatment. Invasive aspergillosis should be suspected in COPD patients receiving steroid treatment who have extensive pulmonary infiltrates. Survival depends on rapid diagnosis and early appropriate treatment. A decrease or interruption of steroid treatment should be considered as part of the overall therapeutic strategy.
Topics: Aspergillosis; Aspergillus fumigatus; Bronchoalveolar Lavage Fluid; Glucocorticoids; Humans; Lung Diseases, Fungal; Pulmonary Disease, Chronic Obstructive; Risk Factors; Withholding Treatment
PubMed: 15882191
DOI: 10.1111/j.1469-0691.2005.01143.x