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Infectious Disease Clinics of North... Jun 2021The spectrum of disease produced by Aspergillus species ranges from allergic syndromes to chronic pulmonary conditions and invasive infections. Invasive aspergillosis is... (Review)
Review
The spectrum of disease produced by Aspergillus species ranges from allergic syndromes to chronic pulmonary conditions and invasive infections. Invasive aspergillosis is a major cause of morbidity and mortality in immunocompromised patients. Risk factors continue to evolve and include newer biological agents that target the immune system and postinfluenza infection; and it has been observed following COVID-19 infection. Diagnosis remains a challenge but non-culture-based methods are available. Antifungal resistance has emerged. Voriconazole remains the treatment of choice but isavuconazole and posaconazole have similar efficacy with less toxicity. Combination therapy is used with extensive infection and in severe immunosuppression.
Topics: Antifungal Agents; Aspergillosis; Aspergillus; COVID-19; Disease Susceptibility; Drug Resistance, Fungal; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Risk Factors
PubMed: 34016284
DOI: 10.1016/j.idc.2021.03.008 -
Clinical Microbiology Reviews Dec 2019is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This... (Review)
Review
is a saprotrophic fungus; its primary habitat is the soil. In its ecological niche, the fungus has learned how to adapt and proliferate in hostile environments. This capacity has helped the fungus to resist and survive against human host defenses and, further, to be responsible for one of the most devastating lung infections in terms of morbidity and mortality. In this review, we will provide (i) a description of the biological cycle of ; (ii) a historical perspective of the spectrum of aspergillus disease and the current epidemiological status of these infections; (iii) an analysis of the modes of immune response against in immunocompetent and immunocompromised patients; (iv) an understanding of the pathways responsible for fungal virulence and their host molecular targets, with a specific focus on the cell wall; (v) the current status of the diagnosis of different clinical syndromes; and (vi) an overview of the available antifungal armamentarium and the therapeutic strategies in the clinical context. In addition, the emergence of new concepts, such as nutritional immunity and the integration and rewiring of multiple fungal metabolic activities occurring during lung invasion, has helped us to redefine the opportunistic pathogenesis of .
Topics: Antifungal Agents; Aspergillosis; Aspergillus fumigatus; Disease Susceptibility; History, 21st Century; Host-Pathogen Interactions; Humans; Immunity; Immunocompromised Host; Public Health Surveillance; Treatment Outcome; Virulence
PubMed: 31722890
DOI: 10.1128/CMR.00140-18 -
Internal Medicine Journal Nov 2021Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment...
Invasive aspergillosis (IA) in haematology/oncology patients presents as primary infection or breakthrough infection, which can become refractory to antifungal treatment and has a high associated mortality. Other emerging patient risk groups include patients in the intensive care setting with severe respiratory viral infections, including COVID-19. These guidelines present key diagnostic and treatment recommendations in light of advances in knowledge since the previous guidelines in 2014. Culture and histological-based methods remain central to the diagnosis of IA. There is increasing evidence for the utility of non-culture methods employing fungal biomarkers in pre-emptive screening for infection, as well as for IA diagnosis when used in combination. Although azole resistance appears to be uncommon in Australia, susceptibility testing of clinical Aspergillus fumigatus complex isolates is recommended. Voriconazole remains the preferred first-line antifungal agent for treating primary IA, including for extrapulmonary disease. Recommendations for paediatric treatment broadly follow those for adults. For breakthrough and refractory IA, a change in class of antifungal agent is strongly recommended, and agents under clinical trial may need to be considered. Newer immunological-based imaging modalities warrant further study, while surveillance for IA and antifungal resistance remain essential to informing the relevance of current treatment recommendations.
Topics: Adult; Antifungal Agents; Aspergillosis; Aspergillus fumigatus; COVID-19; Child; Drug Resistance, Fungal; Humans; SARS-CoV-2; Voriconazole
PubMed: 34937136
DOI: 10.1111/imj.15591 -
Clinical Infectious Diseases : An... Aug 2016It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with...
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Topics: Amphotericin B; Antifungal Agents; Aspergillosis; Azoles; Echinocandins; Humans; Infectious Disease Medicine; Societies, Medical; United States
PubMed: 27365388
DOI: 10.1093/cid/ciw326 -
Molecular Aspects of Medicine Dec 2023Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or... (Review)
Review
Invasive fungal diseases are common complications in critically ill patients and in those with significant underlying imbalanced immune systems. Fungal co-, and/or super-infections are emerging and have become a rising concern within the last few years. In Europe, cases of candidiasis and aspergillosis dominate, followed by mucormycosis in India. Epidemiological studies show an increasing trend in the incidence of all three entities. Parallel to this, a shift within the underlying fungal pathogens is observed. More non-albicans Candida infections and aspergillosis with cryptic species are on the rise; cryptic species may cover intrinsic resistance to azoles and other antifungal drugs. The recent COVID-19 pandemic led to a significantly increasing incidence of invasive fungal diseases among hospitalized patients.
Topics: Humans; Pandemics; Mycoses; Antifungal Agents; Aspergillosis
PubMed: 37804792
DOI: 10.1016/j.mam.2023.101215 -
Infectious Disease Clinics of North... Mar 2016Aspergillosis remains a significant cause of morbidity and mortality in the immunocompromised population. The spectrum of disease is broad, ranging from severe and... (Review)
Review
Aspergillosis remains a significant cause of morbidity and mortality in the immunocompromised population. The spectrum of disease is broad, ranging from severe and rapidly fatal infection to noninvasive disease. The diversity of patients and risk factors complicates diagnostic and therapeutic decision-making. Invasive procedures are often precluded by host status; noninvasive diagnostic tests vary in their sensitivity and specificity. Advancements in understanding the pathophysiology of invasive aspergillosis and host genetics in differential risk have also occurred. Future work may assist in therapeutic decision-making and patient prognosis. Voriconazole remains the preferred agent for treatment. Additional alternatives have emerged.
Topics: Antifungal Agents; Aspergillosis; Humans; Immunocompromised Host; Risk Factors
PubMed: 26897064
DOI: 10.1016/j.idc.2015.10.015 -
The New England Journal of Medicine Oct 2021
Review
Topics: Antifungal Agents; Aspergillosis; Drug Therapy, Combination; Humans; Lung
PubMed: 34644473
DOI: 10.1056/NEJMra2027424 -
Virulence Dec 2023Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression,... (Review)
Review
Pulmonary infections caused by the mould pathogen are a major cause of morbidity and mortality globally. Compromised lung defences arising from immunosuppression, chronic respiratory conditions or more recently, concomitant viral or bacterial pulmonary infections are recognised risks factors for the development of pulmonary aspergillosis. In this review, we will summarise our current knowledge of the mechanistic basis of pulmonary aspergillosis with a focus on emerging at-risk populations.
Topics: Humans; Aspergillus fumigatus; Virulence; Aspergillosis; Virulence Factors; Pulmonary Aspergillosis
PubMed: 36752587
DOI: 10.1080/21505594.2023.2172264 -
The American Journal of Medicine Jun 2020Aspergillus spp. is a ubiquitous mold found commonly in our environment that can cause a spectrum of pulmonary disorders, ranging from a hypersensitivity reaction to an... (Review)
Review
Aspergillus spp. is a ubiquitous mold found commonly in our environment that can cause a spectrum of pulmonary disorders, ranging from a hypersensitivity reaction to an acutely invasive disease with significant mortality. Allergic bronchopulmonary aspergillosis results from airway hypersensitivity from aspergillus colonization almost exclusively in patients with asthma and cystic fibrosis. Chronic pulmonary aspergillosis typically presents in immunocompetent patients with underlying lung pathology. Treatment is primarily with antifungal agents; however, other measures such as surgical resection may be necessary. Invasive pulmonary aspergillosis is a severe infection in immunocompromised patients and is characterized by invasion of pulmonary vasculature by the Aspergillus hyphae. Recent advances in the diagnosis and management of invasive pulmonary aspergillosis include emerging risk factors such as critically ill patients, and those with chronic obstructive pulmonary disease and liver disease. In addition, noninvasive biomarkers have made it easier to suspect and diagnose invasive pulmonary aspergillosis. There are more effective and better-tolerated antifungal agents that have improved patient outcomes. This review introduces the spectrum of pulmonary aspergillosis geared toward generalists, including disease manifestations, most recent diagnostic criteria, and first-line treatment options. Involving a multidisciplinary team is vital to the early diagnosis and management of these diseases.
Topics: Antifungal Agents; Aspergillosis, Allergic Bronchopulmonary; General Practice; Humans; Immunocompromised Host; Invasive Pulmonary Aspergillosis; Pulmonary Aspergillosis
PubMed: 32240631
DOI: 10.1016/j.amjmed.2020.02.025 -
Mycopathologia Oct 2023Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of... (Review)
Review
Despite improvements in treatment and diagnostics over the last two decades, invasive aspergillosis (IA) remains a devastating fungal disease. The number of immunocompromised patients and hence vulnerable hosts increases, which is paralleled by the emergence of a rise in IA cases. Increased frequencies of azole-resistant strains are reported from six continents, presenting a new challenge for the therapeutic management. Treatment options for IA currently consist of three classes of antifungals (azoles, polyenes, echinocandins) with distinctive advantages and shortcomings. Especially in settings of difficult to treat IA, comprising drug tolerance/resistance, limiting drug-drug interactions, and/or severe underlying organ dysfunction, novel approaches are urgently needed. Promising new drugs for the treatment of IA are in late-stage clinical development, including olorofim (a dihydroorotate dehydrogenase inhibitor), fosmanogepix (a Gwt1 enzyme inhibitor), ibrexafungerp (a triterpenoid), opelconazole (an azole optimized for inhalation) and rezafungin (an echinocandin with long half-life time). Further, new insights in the pathophysiology of IA yielding immunotherapy as a potential add-on therapy. Current investigations show encouraging results, so far mostly in preclinical settings. In this review we discuss current treatment strategies, give an outlook on possible new pharmaceutical therapeutic options, and, lastly, provide an overview of the ongoing research in immunotherapy for IA.
Topics: Humans; Aspergillosis; Antifungal Agents; Mycoses; Invasive Fungal Infections; Azoles; Drug Resistance, Fungal
PubMed: 37100963
DOI: 10.1007/s11046-023-00727-z