Aspergillosis Treatment & Management

  • Author: Eloise M Harman, MD; Chief Editor: Zab Mosenifar, MD   more...
 
Updated: Sep 16, 2011
 

Medical Care

The treatment of invasive aspergillosis and chronic necrotizing aspergillosis differs significantly from the treatment of allergic bronchopulmonary aspergillosis (ABPA) and aspergilloma.

Invasive aspergillosis [17, 18]

This is often rapidly progressive and has a high mortality rate; therefore, preventive therapy and rapid institution of therapy in patients in whom invasive aspergillosis is suggested may be lifesaving. Prophylactic antifungal therapy and the use of laminar airflow (LAF) or high-efficiency particulate air (HEPA) filtration of patient rooms in patients who receive bone marrow transplants and other high-risk patients may prevent invasive aspergillosis. In patients with solid organ transplants, especially lung, in whom Aspergillus is cultured from sputum without evidence of pneumonia (colonization), inhaled amphotericin B may be administered.

When high-risk patients develop a compatible clinical picture, empiric treatment for aspergillosis should be initiated as diagnostic testing is undertaken. Voriconazole is now considered the drug of choice for invasive aspergillosis because of better tolerance and improved survival with its use when compared with amphotericin.[19] Posaconazole, amphotericin B, or amphotericin B lipid formulations may be considered as empiric therapy in critically ill patients if the clinical picture, particularly the presence of sinusitis, could be compatible with mucormycosis, because voriconazole is ineffective for Zygomycetes infection. Caspofungin has also been approved for treatment of invasive aspergillosis in patients who are unable to tolerate or are resistant to other therapies.[20] Initial combination therapy is usually not indicated and should generally be reserved for treatment failures.[21]

If possible, the level of immunosuppression should be decreased. For example, patients who are neutropenic may receive growth factors (ie, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor), and patients with certain types of transplants, in which transplanted organ dysfunction will not be life threatening (eg, renal transplant), may have immunosuppressive medications, including corticosteroids, reduced or discontinued.

Combination antifungal therapy is sometimes used for patients whose disease progresses while on single-drug therapy. Concomitant therapy with azole antifungals and amphotericin is controversial because the azole antifungals decrease amphotericin-binding sites and may therefore diminish its effectiveness. Be alert to the possibility of diminished effectiveness of amphotericin in any patient who has received prior treatment with an azole antifungal, including voriconazole, itraconazole, fluconazole, or ketoconazole. Newer antifungal azoles are under study (eg, ravuconazole) and may be available for compassionate use in patients in whom other therapies have failed. Posaconazole, a new triazole, has been approved by the US Food and Drug Administration.[22]

Aspergilloma

Treatment is considered when patients become symptomatic, usually with hemoptysis. Surgical resection is curative but may not be possible in patients with limited pulmonary function. Oral itraconazole may provide partial or complete resolution of aspergillomas in 60% of patients. Successful intracavitary treatment, using CT-guided, percutaneously placed catheters to instill amphotericin alone or in combination with other drugs, including acetylcysteine and aminocaproic acid, has been reported in small numbers of patients.[23]

Bronchial artery embolization may be used for life-threatening hemoptysis in patients thought to have insufficient pulmonary reserve to tolerate surgery or in patients with recurrent hemoptysis (eg, patients with CF in whom hemoptysis may be related to underlying bronchiectasis with or without aspergilloma).[24] Bronchial artery embolization requires a skilled and experienced radiologist because localizing the abnormal vessel(s) may be challenging. Because the anterior spinal arteries may originate from the bronchial vessels, serious neurologic complications, although rare, may occur.

Allergic bronchopulmonary aspergillosis

This is a hypersensitivity reaction that requires treatment with oral corticosteroids. Inhaled steroids are not effective.

Adding oral itraconazole to steroids in patients with recurrent or chronic ABPA may be helpful.[25, 26, 27, 28] This may allow more rapid resolution of infiltrates and symptoms, facilitating steroid tapering or lowering the needed maintenance corticosteroid dosage. In CF patients with ABPA, the concomitant use of itraconazole and inhaled corticosteroids may increase the risk of adrenal insufficiency.

Patients who have associated allergic fungal sinusitis benefit from surgical resection of obstructing nasal polyps and inspissated mucus in addition to corticosteroid therapy. Nasal washes with amphotericin or itraconazole have also been used.

Case reports have described the beneficial use of the anti-IgE monoclonal antibody omalizumab (Xolair) in patients with ABPA.[29]

Chronic necrotizing pulmonary aspergillosis

Treatment consists of therapy with voriconazole, or, in some cases, itraconazole (if expense is an issue), caspofungin, or amphotericin B or amphotericin lipid formulation. A prolonged course of therapy with the goal of radiographic resolution is needed. In addition, reduction or elimination of immunosuppression should be attempted, if possible.

Surgical resection may be considered when localized disease fails to respond to antifungal therapy.

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Surgical Care

Invasive aspergillosis and CNPA

Surgical resection is a consideration for localized chronic necrotizing pulmonary aspergillosis (CNPA) that has failed to respond to prolonged antifungal therapy.[30] Aspergillomas may occasionally form in areas of necrotizing pneumonia. These necrotic areas may bleed, sometimes massively, necessitating consideration of surgical resection. Patients may be high-risk surgical candidates because of underlying disease, coagulopathy, or thrombocytopenia and limited pulmonary reserve.

Aspergilloma

Surgical resection may be considered for massive hemoptysis if pulmonary function is sufficient enough for this sort of intervention. Assessment of operative risk necessitates obtaining pulmonary function studies, arterial blood gas determinations, and, possibly, split lung function studies (eg, quantitative perfusion lung scanning). Because aspergilloma occurs in cavitary areas, the affected lung may not be functional. Surgical resection may be difficult because of scarring, pleural adhesion, and the presence of abnormal vasculature.

Allergic bronchopulmonary aspergillosis

Areas of mucoid impaction may have a masslike appearance and are sometimes resected as an undiagnosed lung mass; however, steroid therapy and oral itraconazole therapy are preferred. Allergic fungal sinusitis usually requires endoscopic sinus surgery to improve drainage.

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Consultations

Consultation with a pulmonologist may be helpful for patients suggested to have invasive aspergillosis or chronic necrotizing Aspergillus pneumonia in order to establish a definitive diagnosis. Once the diagnosis is established, consultation with an infectious diseases specialist is usually helpful in management, especially if patients do not respond to initial fungal therapy.

Patients with ABPA or allergic fungal sinusitis should be treated by a pulmonologist or allergist familiar with the management of these conditions. Consultation with a pulmonologist is also indicated in patients with aspergilloma. Input from a thoracic surgeon may also be needed if surgical resection is feasible. In selected patients, consultation with an invasive radiologist may be indicated for CT-directed catheter placement to allow intracavitary therapy or bronchial artery embolization.

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Contributor Information and Disclosures
Author

Eloise M Harman, MD  Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, University of Florida College of Medicine

Eloise M Harman, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Chest Physicians, American Medical Women's Association, American Thoracic Society, Phi Beta Kappa, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Oleh Wasyl Hnatiuk, MD  Program Director, National Capital Consortium, Pulmonary and Critical Care, Walter Reed Army Medical Center; Associate Professor, Department of Medicine, Uniformed Services University of Health Sciences

Oleh Wasyl Hnatiuk, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H  Professor, Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Southern California Keck School of Medicine

Om Prakash Sharma, MD, FRCP, FCCP, DTM&H is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Osler Society, American Thoracic Society, New York Academy of Medicine, and Royal Society of Medicine

Disclosure: Nothing to disclose.

Timothy D Rice, MD  Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, St Louis University School of Medicine

Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD  Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Professor and Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society

Disclosure: Nothing to disclose.

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