Practice guidelines for diseases caused by Aspergillus

Aspergillosis comprises a variety of manifestations of infection. These gui delines are directed to 3 principal entities: invasive aspergillosis, invol ving several organ systems (particularly pulmonary disease); pulmonary aspe rgilloma; and allergic bronchopulmonary aspergillosis. The recommendations are distilled in this summary, but the reader is encouraged to review the m ore extensive discussions in subsequent sections, which show the strength o f the recommendations and the quality of the evidence, and the original pub lications cited in detail. Invasive aspergillosis. Because it is highly lethal in the immunocompromise d 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, with out definitive proof (BIII). Intravenous therapy should be: used initially in rapidly progressing disease (BIII). The largest therapeutic experience i s with amphotericin B deoxycholate, which should be given at maximum tolera ted doses (e.g., 1-1.5 mg/kg/d) and should be continued. despite modest inc reases in serum creatinine levels (BIII). Lipid formulations of amphoterici n are indicated for the patient who has impaired renal Function or who deve lops nephrotoxicity while receiving deoxycholate amphotericin (AII). Oral i traconazole is an alternative for patients who can take oral medication. ar e 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 bey ond resolution of disease and reversible underlying predispositions (BIII). Adjunctive therapy (particularly surgery and combination chemotherapy. als o immunotherapy), may be useful in certain situations (CIII). Aspergilloma. The optimal treatment strategy for aspergilloma is unknown. T herapy is predominantly directed at preventing life-threatening hemoptysis. Surgical removal of aspergilloma is definitive treatment, but because of s ignificant morbidity and mortality it should be reserved for high-risk pati ents such its those with episodes of life-threatening hemoptysis, and consi dered for patients with underlying sarcoidosis, immunocompromised patients, and those with increasing Asper Aspergillus-specific IgG titers (CIII). Su rgical candidates would need to have adequate pulmonary function to undergo the operation. Bronchial artery embolization rarely produces a permanent s uccess. but may be useful as a temporizing procedure in patients with life- threatening hemoptysis. Endobronchial and intracavitary instillation of ant ifungals or oral itraconazole may be useful for this condition. Since the m ajority of aspergillomas do not cause life-threatening hemoptysis, the morb idity and cost of treatment must be weighed against the clinical benefit. Allergic bronchopulmonary aspergillosis (APBA). Although no well-designed s tudies have been carried out, the available data support the use of cortico steroids for acute exacerbations of ABPA (AII). Neither the optimal cortico steroid dose nor the duration of therapy has been standardized, but limited data suggest the starting dose should be similar to 0.5 mg/kg/d of prednis one. 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 s ignificant 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 ast hmatic exacerbations in a patient with ABPA suggest that chronic corticoste roid therapy should be used (BIII). Itraconazole appears useful as a cortic osteroid sparing agent (BII). Although the frequency of these diseases is on the rise, there is a paucity of randomized comparative trials involving these entities; therefore, the recommendations represent a compromise and consensus among students of thes e diseases (i.e., the authors). They have synthesized the recommendations f rom published and personal experience, including case series, open trials, and any comparative trials, as indicated.