Definition and EtiologyTop
Aspergillus is a fungus (mold) commonly found in the environment, including hospitals. The fungus can colonize the respiratory tract, especially in people with chronic respiratory diseases. Abnormal phagocytosis allows for the transition from colonization to invasion.
Invasive aspergillosis is most commonly caused by Aspergillus fumigatus, Aspergillus flavus, Aspergillus niger, or Aspergillus terreus. Risk factors include neutropenia, immunosuppression including chronic glucocorticoid use and antirejection regimens, prior antibiotic treatment, and chronic pulmonary disease.
Clinical features of invasive aspergillosis include fever, pleuritic pain, and hemoptysis. Chest radiographs may reveal peripheral solitary or multiple nodules, some of them with features of necrosis. CT scans reveal focal interstitial opacities surrounded by a cloud of a lower density image (halo sign). Clinical features of acute aspergillosis develop within several days; subacute presentation may develop within weeks to a few months.
The diagnosis of pneumonia is confirmed only if microscopic examination reveals the presence of fungi in lung biopsy specimens (in immunosuppressed patients also in bronchoalveolar lavage) and Aspergillus spp have been isolated in culture of the same specimen. An assay detecting Aspergillus spp antigen (galactomannan) in serum or bronchoalveolar lavage is useful in diagnostics. Using an optical density index (ODI) of 0.5 as a cutoff value, the sensitivity and specificity of the test to detect invasive aspergillosis is estimated to be ~80%. At a cutoff value of ODI 1.0, sensitivity is reduced to ~70% and specificity increased to ~90%. A positive sputum culture result is of low diagnostic value.
Use IV voriconazole (6 mg/kg every 12 hours for 2 doses on day 1, followed by 4 mg/kg bid; after achieving clinical improvement, you may switch to oral administration [4 mg/kg bid] starting on day 7). Alternatively, you may use IV amphotericin B as a liposomal formulation 3 to 5 mg/kg/d, as a lipid complex 5 mg/kg/d, or as a colloidal dispersion 3 to 4 mg/kg/d; use of amphotericin deoxycholate 0.7 to 1 mg/kg/d (maximum, 1.5 mg/kg/d) is associated with a higher risk of nephrotoxicity and other adverse effects.
In patients with less severe disease and patients who have achieved clinical improvement, consider itraconazole (200 mg tid for 3 days followed by 200 mg bid for tablets; note that dose depends on the formulation and that absorption can be variable) or oral voriconazole 200 mg bid for 2 to 5 months. In patients with a single lesion (particularly those with hemoptysis) and patients with lesions adjacent to major blood vessels, the pericardium, penetrating into the pleural cavity, or infiltrating the ribs, surgical resection of the lesion may be indicated during antifungal treatment. In patients with resistance to or intolerance of amphotericin or azole antifungal agents, use caspofungin (70 mg/d IV; in patients with a body weight ≤80 kg administer 50 mg/d from day 2 of treatment), micafungin (100-150 mg/d IV), or posaconazole (start from 200 mg orally qid, after clinical stabilization of the patient change to 400 mg orally bid).
The antifungal therapy should be continued until all signs and symptoms of the infection have been resolved and will often be prolonged in patients with persistent immunologic impairment. Although the duration has not been well established, treatment is generally continued for a minimum of 6 to 12 weeks. Primary combination therapy is not routinely recommended based on the lack of clinical data but may be considered for individual patients.