Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content + Print Section ++ For further information, see CMDT Part 36-07: Aspergillosis + Key Features Print Section ++ ++ Essentials of Diagnosis ++ Most common cause of noncandidal invasive fungal infection in transplant recipients and in patients with hematologic malignancies Predisposing factors: leukemia, bone marrow or organ transplant, late HIV infection Lungs, sinuses, and CNS are most common disease sites Serologic detection in serum or other body fluids Useful for early diagnosis and treatment However, multiple determinations should be done and usefulness is decreased in patients receiving anti-mold prophylaxis (ie, voriconazole or posaconazole) ++ General Considerations ++ Aspergillus fumigatus is the usual cause of aspergillosis, although many species of Aspergillus can cause disease Clinical illness results from abnormal immune response or tissue invasion Allergic bronchopulmonary aspergillosis (ABPA) occurs in persons with asthma or cystic fibrosis Invasive aspergillosis Usually occurs in profound immunodeficiency, particularly in patients Who have undergone hematopoietic stem cell transplantation With prolonged severe neutropenia Can occur among critically ill immunocompetent patients ++ Clinical Findings ++ Allergic forms of aspergillosis ABPA causes worsening bronchospasm in patients with asthma or cystic fibrosis Allergic aspergillus sinusitis produces a chronic sinus inflammation characterized by eosinophilic mucous and noninvasive hyphal elements Chronic aspergillosis Cough Shortness of breath Weight loss Malaise Invasive aspergillosis Pulmonary disease most common Invasive sinus disease + Diagnosis Print Section ++ ++ ABPA Eosinophilia High levels of total IgE, and IgE and IgG specific for Aspergillus in the blood Chronic aspergillosis Disease manifestations range from aspergillomas that develop in a lung cavity to chronic fibrosing pulmonary aspergillosis in which the majority of lung tissue is replaced with fibrosis Invasive aspergillosis Patchy infiltration leading to a severe necrotizing pneumonia Tissue infarction (development of pleuritic chest pain and elevation of serum lactate dehydrogenase [LD]) Hematogenous dissemination to the CNS, skin, and other organs Blood cultures have very low yield Detection of galactomannan by enzyme-linked immunosorbent assay (ELISA) or Aspergillus DNA by polymerase chain reaction (PCR); multiple determinations should be done Definitive diagnosis requires demonstration of Aspergillus in tissue or culture from a sterile site Chest CT scan may show indicative characteristics (eg, "halo sign") + Treatment Print Section ++ ++ ABPA For acute exacerbations, prednisone, 0.5 mg/kg/day orally tapered slowly over several months Itraconazole, 200 mg orally once daily for 16 weeks, appears to improve pulmonary function and decrease corticosteroid requirements, although voriconazole is increasingly being used Allergic aspergillus sinusitis Topical corticosteroids cornerstone of therapy Itraconazole is best studied agent Chronic aspergillosis Surgical resection remains most effective therapy for symptomatic aspergilloma Other forms of chronic aspergillosis are generally treated with at least 4–6 months of oral azole therapy Itraconazole, 200 mg twice daily Voriconazole, 200 mg twice daily Posaconazole, 300 mg daily Invasive aspergillosis Reversal of any correctable immunosuppression Rapid institution of voriconazole (6 mg/kg intravenously twice on day 1 and then 4 mg/kg every 12 hours thereafter) is considered optimal therapy Combination therapy of anidulofungin (200 mg on day 1 and then 100 mg daily) plus voriconazole A randomized controlled trial did not find an overall benefit However, patients in whom galactomannan was detected who received combination therapy had better outcomes Isovuconazole (372 mg of prodrug on days 1 and 2 and then 372 mg once daily) was equivalent to voriconazole Alternatives include A lipid formulation of amphotericin B, 3–5 mg/kg/day Caspofungin, 70 mg intravenously on day 1 and then 50 mg/day thereafter Posaconazole oral tablets, 300 mg twice daily on day 1 and then 300 mg daily thereafter Oral dosing of voriconazole at 4 mg/kg twice daily can be used for less serious infections or as a step-down strategy after intravenous therapy Surgical debridement Generally done for sinusitis Can be useful for focal pulmonary lesions, especially for treatment of life-threatening hemoptysis and infections recalcitrant to medical therapy Therapeutic drug monitoring should be considered for both voriconazole and posaconazole given variations in metabolism and absorption + Outcome Print Section ++ ++ Prognosis ++ Invasive aspergillosis Can be life-threatening, particularly in profound immunodeficiency and prolonged severe neutropenia Reversal of underlying immunosuppression is key to patient outcome Higher galactomannan levels correlate with increased mortality and failure of galactomannan levels to fall in response to therapy portends a worse outcome + References Print Section ++ + +Gago S et al. Pathophysiological aspects of Aspergillus colonization in disease. Med Mycol. 2019 Apr 1;57(Supplement 2):S219–227. [PubMed: 30239804] + +Jenks JD et al. Treatment of aspergillosis. J Fungi (Basel). 2018 Aug 19;4(3):E98. [PubMed: 30126229] + +Kanj A et al. The spectrum of pulmonary aspergillosis. Respir Med. 2018 Aug;141:121–31. [PubMed: 30053957] + +Patterson TF et al. Practice guidelines for the diagnosis and management of aspergillosis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Aug 15; 63(4):e1–60. [PubMed: 27365388] + +Takazono T et al. Recent advances in diagnosing chronic pulmonary aspergillosis. Front Microbiol. 2018 Aug 17;9:1810. [PubMed: 30174658]