Aspergillosis

SOURCE

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.

DEFINITION

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

ETIOLOGY

• 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.

PATHOPHYSIOLOGY

• Impaired phagocytosis required for development of invasive disease.

EPIDEMIOLOGY

• 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.

RISK FACTORS

• 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)

CLINICAL PRESENTATION

• Lung is most common site of invasion.

SIGNS AND SYMPTOMS

• 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.

DIAGNOSIS

MEANS OF CONFIRMATION AND DIAGNOSIS

• 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.

LABORATORY TESTS

• 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.

IMAGING

• 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.

DIFFERENTIAL DIAGNOSIS

• Pneumonia

• Lung abscess.

• Pulmonary embolus.

• Tuberculosis

TREATMENT: PHARMACOLOGIC THERAPY

• Start empiric antifungal therapy in patients at highest risk for invasive disease (acute ...