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SOURCE

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Source: Carver PL. Invasive fungal infections. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. http://accesspharmacy.mhmedical.com/content.aspx?bookid=1861&sectionid=146073167. Accessed February 23, 2017.

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DEFINITION

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  • Spectrum of diseases attributed to allergy, colonization, or tissue invasion caused by members of the fungal genus Aspergillus

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ETIOLOGY

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  • Opportunistic fungal infection caused by Aspergillus species.

  • Generally acquired by inhalation of airborne conidia small enough (2.5–3 μm) to reach alveoli or paranasal sinuses.

  • Other causative agent: mold that grows in soil, water, decaying vegetation, and organic debris.

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PATHOPHYSIOLOGY

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  • Impaired phagocytosis required for development of invasive disease.

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EPIDEMIOLOGY

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  • Three of 300 species of Aspergillus are most commonly pathogenic: A. fumigatus, A. flavus, and A. niger.

  • Second most common invasive fungal infection behind candidiasis.

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RISK FACTORS

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  • Prolonged neutropenia.

  • Chronic administration of glucocorticoids (particularly chronic administration or higher dosages)

  • Cytotoxic agent administration.

  • Recent or concurrent therapy with broad-spectrum antimicrobials.

  • Bone marrow transplant.

  • Chronic granulomatous disease.

  • Leukemia.

  • Lymphoma.

  • Acute rejection of transplanted organ.

  • HIV infection (uncommon)

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CLINICAL PRESENTATION

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  • Lung is most common site of invasion.

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SIGNS AND SYMPTOMS
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  • Lung is most common site of invasion. Patients often present with classic signs and symptoms of acute pulmonary embolus:

    • Pleuritic chest pain.

    • Fever.

    • Hemoptysis.

    • Friction rub.

  • Neutropenic patients develop acute necrotizing, pyogenic pneumonitis due to hyphae invasion of walls of bronchi and surrounding parenchyma.

  • In immunocompromised host:

    • Vascular invasion leads to thrombosis, infarction, necrosis of tissue, and dissemination to other tissues and organs in the body.

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DIAGNOSIS

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MEANS OF CONFIRMATION AND DIAGNOSIS
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  • Normal commensal in GI tract and respiratory secretions, therefore definitive diagnosis is difficult.

  • Demonstration of Aspergillus by repeated culture and microscopic examination of tissue provides most accurate diagnosis.

  • Lung biopsy can be performed for a definitive diagnosis, but can be difficult to obtain.

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LABORATORY TESTS
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  • Blood cultures.

  • Enzyme-linked immunosorbent assay (ELISA) of serum or other body fluids used to detect galactomannan, an antigen released from Aspergillus to Aspergillus species.

  • (1,3)-β-D-glucan (BG) test to detect β-D-glucan in serum or other body fluids.

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IMAGING
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  • CT scan.

    • Early manifestations may show characteristic “halo sign.”

    • Lesion manifest as diffuse pulmonary infiltrates, consolidation, ground glass opacities, or the crescent sign.

  • Chest radiographs.

    • Wedge-shaped, pleural-based infiltrates.

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DIFFERENTIAL DIAGNOSIS
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TREATMENT: PHARMACOLOGIC THERAPY

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  • Start empiric antifungal therapy in patients at highest risk for invasive disease (acute leukemia and bone marrow transplant recipients) with prolonged neutropenia who are persistently febrile despite ...

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