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The Fungi
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The genus Aspergillus includes many species, but most disease in humans is caused by Aspergillus fumigatus. The aspergilli are common saprophytes which produce hyphal growth both in the environment, where they are ubiquitous, and in the host. Despite daily exposure to aspergillus conidia, invasive aspergillosis occurs only in the severely compromised host. Either a lack of PMNs or improperly functioning PMNs predispose the host to life-threatening aspergillosis. Neutropenia is in fact the greatest single risk factor for invasive aspergillosis and occurs primarily in patients undergoing immunosuppressive chemotherapy or radiation therapy for cancers or transplants. Antifungal therapy is attempted in these cases, but the prognosis is generally poor due to the underlying condition of the host.
Aspergillosis and Mucormycosis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
Alayn R. Waldorf, Richard D. Diamond
Diagnostic tests have focused on developing assays to detect either antibody to Aspergillus antigens99,101-105 or the actual antigens themselves.106–109 Since patients with invasive aspergillosis usually have an altered immune response, seroconversion may be delayed or may not occur at all. Serum precipitins as determined by counterimmunoelectrophoresis, enzyme-linked immunoabsorbant assay, and passive hemagglutination are positive in 70 to 80% of patients with invasive pulmonary aspergillosis.99 Advocates of these procedures believe that an early and accurate diagnosis of invasive aspergillosis can be accomplished by monitoring with immunodiffusion, counterimmunoelectrophoresis, and other tests for demonstrating lines of identity, critical titers, and seroconversion and/or titer or band changes.
Infections Related to Steroids and Immunosuppressive Agents in the Critical Care Unit
Published in Cheston B. Cunha, Burke A. Cunha, Infectious Diseases and Antimicrobial Stewardship in Critical Care Medicine, 2020
The increasing risk of fungal infections was reported with anti-TNF agents and biologic agents targeting IL-17 (e.g., secukinumab). The study analyzing BIOBADASER data from Spain reported Candida albicans as the most common fungus among anti-TNF users in RA patients, with the other fungi being Aspergillus fumigatus, Malassezia furfur, and Pityrosporum ovale. Invasive aspergillosis with pulmonary presentations or dissemination must be kept in mind in this population. Histoplasmosis, a life-threatening granulomatous infection, has mainly been reported in endemic areas (Northern America, Central and South America, Africa, Asia, and Australia). Most of the cases have lung involvement and are sometimes associated with fever, skin or mucous disorders, hepatosplenomegaly, and adenomegaly. Cryptococcosis, coccidioidomycosis, mucormycosis, and blastomycosis are other occasionally reported fungal infections.
Invasive Aspergillus infection of middle ear in a patient treated with secukinumab, methotrexate, and corticosteroids for psoriasis and psoriatic arthritis
Published in Journal of Dermatological Treatment, 2022
Filip Rob, Lukáš Školoudík, Viktor Chrobok, Jana Dědková, Petra Kašparová, Lucie Podrazilová
Invasive aspergillosis is an opportunistic infection most commonly seen in patients with prolonged neutropenia (e.g. immunosuppressive patients because of solid or bone marrow transplantation). Modern biologic therapies, including TNF-alpha and IL-17 inhibitors, also interfere with neutrophil function. Only sporadic cases of invasive aspergillosis have been reported with infliximab and etanercept treatment in patients with inflammatory bowel disease and rheumatoid arthritis (5). Invasive Aspergillus infection has not been reported with secukinumab or ixekizumab therapy, even in long-term safety studies lasting 5 years (3,6). With our patient, the development of this opportunistic infection could be facilitated by the current therapy with methotrexate. Like treatment with methotrexate (usually a high dose), cases of aspergillosis in transplant patients have been rarely described. If aspergillosis is suspected, an X-ray or CT scan (according to the localization) should be performed. These examinations reveal a fungal mass (aspergilloma) and characteristic signs of invasive aspergillosis. Non-culture-based tests (galactomannan or β(1,3)-glucan test) can also help diagnose the disease. A sputum examination (culture, PCR) can be used in bronchopulmonary aspergillosis, but tissue biopsy is usually necessary to confirm the diagnosis (7).
Pharmacological management of antifungal agents in pulmonary aspergillosis: an updated review
Published in Expert Review of Anti-infective Therapy, 2022
Daniel Echeverria-Esnal, Clara Martín-Ontiyuelo, Maria Eugenia Navarrete-Rouco, Jaime Barcelo-Vidal, David Conde-Estévez, Nuria Carballo, Marta De-Antonio Cuscó, Olivia Ferrández, Juan Pablo Horcajada, Santiago Grau
Additionally, dosage recommendations are another determining point in care. Patients diagnosed with pulmonary aspergillosis present special characteristics that complicate dosing. Although TDM is routinely recommended, it may not be always available. Conversely, if available, results during TDM may take some time to arrive. Thus, clinicians must make decisions regarding dosing without considering TDM. Whereas data on obesity or critically ill patients are available for some antifungals (although, of limited quality since most come from case reports) information on dosage recommendations in patients with cachexia or hypoalbuminemia is scarce. However, this insight is extremely important and relevant, given the protein binding of most antifungal agents and the risk of plasma drug concentrations alterations entailed. Similarly, available information related to dosing and TDM in other forms such as chronic pulmonary or allergic bronchopulmonary aspergillosis is limited. Patients diagnosed with these forms will vary from those with invasive aspergillosis. More data are needed on therapeutic goals and appropriate dosing in this series of patients, especially as they experience prolonged treatment and have high rates of side effects.
Azole resistance in Aspergillus species: promising therapeutic options
Published in Expert Opinion on Pharmacotherapy, 2021
Shirisha Pasula, Pranatharthi H. Chandrasekar
Aspergillus fumigatus can cause a wide variety of pulmonary fungal diseases, including hypersensitivity pneumonitis, acute invasive aspergillosis (IA), chronic pulmonary aspergillosis (CPA), and allergic bronchopulmonary aspergillosis (ABPA) [1]. The triazoles, itraconazole, isavuconazole, posaconazole, and voriconazole are antifungal agents with potent activity against A. fumigatus. Itraconazole and voriconazole are the preferred agents in patients with chronic pulmonary aspergillosis. Voriconazole and isavuconazole have been studied as first-line agents for the treatment of invasive aspergillosis. Posaconazole is mainly used for prophylaxis against invasive fungal infections in patients with hematological diseases [2–4]. There is an increasing global concern for azole resistance creating difficulty in choosing reliable effective antifungal regimen and is associated with increased mortality. This paper reviews epidemiology, mechanisms and detection of azole resistance, and therapeutic options for azole-resistant Aspergillus infections.