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Detection of Invasive Pulmonary Aspergillosis in Haematological Malignancy Patients by using Lateral-flow Technology
Published on: March 22, 2012
Practice guidelines for diseases caused by Aspergillus. Infectious Diseases Society of America
D A Stevens1, V L Kan, M A Judson
1Dept. of Medicine, Santa Clara Valley Medical Center, San Jose, CA 95128-2699, USA. stevens@leland.stanford.edu
Abstract:
Aspergillosis comprises a variety of manifestations of infection. These guidelines are directed to 3 principal entities: invasive aspergillosis, involving several organ systems (particularly pulmonary disease); pulmonary aspergilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the more extensive discussions in subsequent sections, which show the strength of the recommendations and the quality of the evidence, and the original publications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromised host, even in the face of therapy, work-up must be prompt and aggressive, and therapy may need to be initiated upon suspicion of the diagnosis, without definitive proof (BIII). Intravenous therapy should be used initially in rapidly progressing disease (BIII). The largest therapeutic experience is with amphotericin B deoxycholate, which should be given at maximum tolerated doses (e.g., 1-1.5 mg/kg/d) and should be continued, despite modest increases in serum creatinine levels (BIII). Lipid formulations of amphotericin are indicated for the patient who has impaired renal function or who develops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral itraconazole is an alternative for patients who can take oral medication, are likely to be adherent, can be demonstrated (by serum level monitoring) to absorb the drug, and lack the potential for interaction with other drugs (BII). Oral itraconazole is attractive for continuing therapy in the patient who responds to initial iv therapy (CIII). Therapy should be prolonged beyond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy, also immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. Therapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of significant morbidity and mortality it should be reserved for high-risk patients such as those with episodes of life-threatening hemoptysis, and considered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Aspergillus-specific IgG titers (CIII). Surgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent success, but may be useful as a temporizing procedure in patients with life-threatening hemoptysis. Endobronchial and intracavitary instillation of antifungals or oral itraconazole may be useful for this condition. Since the majority of aspergillomas do not cause life-threatening hemoptysis, the morbidity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed studies have been carried out, the available data support the use of corticosteroids for acute exacerbations of ABPA (AII). Neither the optimal corticosteroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be approximately 0.5 mg/kg/d of prednisone. The decision to taper corticosteroids should be made on an individual basis, depending on the clinical course (BIII). The available data suggest that clinical symptoms alone are inadequate to make such decisions, since significant lung damage may occur in asymptomatic patients. Increasing serum IgE levels, new or worsening infiltrate on chest radiograph, and worsening spirometry suggest that corticosteroids should be used (BII). Multiple asthmatic exacerbations in a patient with ABPA suggest that chronic corticosteroid therapy should be used (BIII). Itraconazole appears useful as a corticosteroid sparing agent (BII). (ABSTRACT TRUNCATED)
Insights
This summary provides guidelines for managing aspergillosis, including invasive infections, aspergilloma, and allergic bronchopulmonary aspergillosis (ABPA). Treatment strategies emphasize prompt diagnosis and tailored therapies for different forms of this fungal infection.
Area of Science:
- Medical Mycology: Focuses on the diagnosis and management of fungal infections caused by Aspergillus species.
- Infectious Diseases: Addresses the clinical manifestations, treatment, and prevention of aspergillosis in various patient populations.
- Pulmonology: Details the pulmonary manifestations of aspergillosis, including invasive disease, aspergilloma, and allergic bronchopulmonary aspergillosis.
Background:
- Aspergillosis presents with diverse clinical manifestations, necessitating distinct management approaches for invasive aspergillosis, pulmonary aspergilloma, and allergic bronchopulmonary aspergillosis (ABPA).
- Prompt diagnosis and aggressive treatment are crucial for invasive aspergillosis, particularly in immunocompromised individuals, due to its high lethality.
Framework:
- Guidelines for invasive aspergillosis recommend prompt work-up and initiation of therapy, potentially before definitive proof, with intravenous amphotericin B deoxycholate as a primary option.
- Management of aspergilloma focuses on preventing hemoptysis, with surgical resection as definitive but reserved for high-risk patients; bronchial artery embolization is a temporizing measure.
- Allergic bronchopulmonary aspergillosis (ABPA) management involves corticosteroids for acute exacerbations, with itraconazole as a potential steroid-sparing agent.
Implementation:
- Intravenous therapy with amphotericin B deoxycholate at maximum tolerated doses is recommended for invasive aspergillosis, with lipid formulations used for renal impairment.
- Oral itraconazole is an alternative for invasive aspergillosis in select patients and for continuing therapy post-initial treatment.
- Corticosteroids are indicated for ABPA exacerbations, guided by clinical and immunological markers, with consideration for chronic therapy in severe cases.
Implications:
- Therapy for invasive aspergillosis should be prolonged beyond disease resolution and underlying predisposition reversal.
- Adjunctive therapies, including surgery, chemotherapy, and immunotherapy, may be beneficial in specific aspergillosis scenarios.
- Careful consideration of treatment morbidity and cost-benefit is essential, especially for aspergilloma where definitive treatment is reserved for high-risk cases.
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