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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. 8 ed. http://accesspharmacy.com/content.aspx?aid=8005562. Accessed June 25, 2012.

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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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  • Opportunistic fungal infection caused by Aspergillus species
  • Generally acquired by inhalation of airborne conidia small enough (2.5–3 mm) to reach alveoli or paranasal sinuses.
  • Other causative agent: mold that grows in soil, water, decaying vegetation, and organic debris

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  • Impaired phagocytosis required for development of invasive disease.

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

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  • Prolonged neutropenia
  • Chronic administration of glucocorticoids
  • Cytotoxic treatment
  • Bone marrow transplant
  • Recent or concurrent therapy with broad-spectrum antimicrobials
  • Chronic granulomatous disease
  • Leukemia
  • Lymphoma
  • Acute rejection of transplanted organ
  • Late HIV infection

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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
    • Wedge-shaped infiltrate on chest radiographs
  • 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.
    • Survival beyond 2–3 weeks is uncommon.

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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.

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Laboratory Tests

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  • Blood cultures
  • Enzyme immunosorbent assay (EIA) of serum or other body fluids used to detect galactomannan, a cell-wall polysaccharide specific to Aspergillus species
  • BG test to detect β-D-glucan in serum or other body fluids

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Imaging

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  • Chest radiograph
  • CT scan may show characteristic halo sign.

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Differential Diagnosis

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  • Survive invasive aspergillosis.

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  • Reverse correctable immunosuppression.

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  • Start empiric antifungal therapy in patients at highest risk for invasive disease (acute leukemia and bone marrow transplant recipients) in any of these conditions:
    • Persistent fever or progressive sinusitis unresponsive to antimicrobial therapy
    • Eschar over nose, sinuses, or palate
    • Presence of characteristic radiographic findings, including wedge-shaped infarcts, nodular densities, or new cavitary lesions
    • Any clinical manifestation suggestive of orbital or cavernous sinus disease or acute vascular event associated with fever
  • Isolation of Aspergillus spp. from nasal or respiratory tract secretions confirmatory evidence in any of previously mentioned clinical settings.
  • Voriconazole is drug of choice for primary therapy:
    • 6 mg/kg IV twice daily on day 1, then 4 mg/kg/day
    • ...

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