Invasive fungal infection

Microbiology

• Aspergillus species
• Mucormycosis
• Cryptococcus?
• Penicillium
• Others...

Epidemiology

• Among patients on posaconazole for a hematologic malignancy or bone marrow transplant, there is an approximately 2% rate of breakthrough infection 1

Classification

• The classification is based on a combination of patient risk factors (host factors), imaging, and mycology 2
• Host factors
  • Recent history of neutropenia (<0.5 × 109 neutrophils/L for >10 days) temporally related to the onset of fungal disease
  • Receipt of an allogeneic stem cell transplant
  • Prolonged use of corticosteroids (excluding ABPA) at a mean minimum dose of 0.3 mg/kg/day of prednisone equivalent for >3 weeks
  •  Treatment with other recognized T cell immunosuppressants, such as cyclosporine, TNF-α inhibitors, specific monoclonal antibodies (such as alemtuzumab), or nucleoside analogues during the past 90 days
  • Inherited severe immunodeficiency (such as chronic granulomatous disease or severe combined immunodeficiency)
• Clinical criteria
  •  Lower respiratory tract fungal disease: the presence of 1 of the following 3 signs on CT
    • Dense, well-circumscribed lesions(s) with or without a halo sign
    • Air-crescent sign
    • Cavity
  • Tracheobronchitis: tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar seen on bronchoscopic analysis
  •  Sinonasal infection: imaging showing sinusitis plus at least 1 of the following 3 signs:
    •  Acute localized pain (including pain radiating to the eye)
    •  Nasal ulcer with black eschar
    •  Extension from the paranasal sinus across bony barriers, including into the orbit
  •  CNS infection: 1 of the following 2 signs
    •  Focal lesions on imaging
    •  Meningeal enhancement on MRI or CT
  •  Disseminated candidiasis: At least 1 of the following 2 entities after an episode of candidemia within the previous 2 weeks:
    •  Small, target-like abscesses (bull's-eye lesions) in liver or spleen
    •  Progressive retinal exudates on ophthalmologic examination
• Mycological criteria
  •  Direct test (cytology, direct microscopy, or culture)
    •  Mold in sputum, bronchoalveolar lavage fluid, bronchial brush, or sinus aspirate samples, indicated by 1 of the following:
    •  Presence of fungal elements indicating a mold
    •  Recovery by culture of a mold (e.g., Aspergillus, Fusarium, Zygomycetes, or Scedosporium species)
  •  Indirect tests (detection of antigen or cell-wall constituents)
    •  Aspergillosis: Galactomannan antigen detected in plasma, serum, bronchoalveolar lavage fluid, or CSF
    •  Invasive fungal disease other than cryptococcosis and zygomycoses: β-d-glucan detected in serum

Proven

• Fungal elements in biopsy of diseased tissue, or highly specific indirect assays
• Includes:
  • Aspergillus in culture
  • Histoplasma capsulatum: intracellular budding yeasts
  • Coccidioides species: spherules
  • Paracoccidioides brasiliensis: large yeasts with multiple daughter yeasts in a “pilot-wheel configuration”
  • Blastomyces dermatitidis: thick-walled, broad-based budding yeasts
• Can include Coccidioides antibodies in CSF, or Cryptococcus capsular antigen in CSF
• Does not include urine antigens

Probable

• Requires a susceptible host, clinical/radiographic features, and mycological evidence

Possible

• Only cases with the appropriate host factors and with sufficient clinical/radiographic evidence without supporting mycological evidence
• Not used for endemic fungi