Invasive fungal infection

Microbiology

• Endemic fungi
  • Histoplasmosis
  • Blastomycosis
  • Coccidioidomycosis
  • Paracoccidioidomycosis
  • Sporotrichosis
  • Penicillium marneffei
• Other fungi
  • Molds
    • Aspergillus species
    • Zygomycosis
    • Fusarium
    • Scedosporium
  • Yeasts
    • Candida
    • Cryptococcus
• Excludes Pneumocystis

Epidemiology

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

Classification (excluding endemic fungi)

Probable invasive pulmonary mold disease

• The classification for probable invasive pulmonary mold disease requires at least one patient risk factor (host factor), one clinical criterion (e.g. imaging), and one mycological criterion 2
• Host factors
  • Recent history of neutropenia (<0.5 × 109 neutrophils/L for >10 days) temporally related to the onset of fungal disease
  • Hematologic malignancy (active, in treatment, or recent)
  • 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 in the past 60 days
  •  Treatment with other recognized T-cell immunosuppressants, such as calcineurin inhibitors, TNF-α inhibitors, specific monoclonal antibodies (such as alemtuzumab), or nucleoside analogues during the past 90 days
  • Treatment with certain B-cell immunosuppressants, including ibrutinib
  • Inherited severe immunodeficiency, such as chronic granulomatous disease, STAT 3 deficiency, or severe combined immunodeficiency
  • Acute graft-versus-host disease grade III or IV, involving gut, lungs, or liver, which is refractory to first-line steroids
• Clinical criteria
  • Pulmonary aspergillosis: any of the following patterns on CT
    • Dense, well-circumscribed lesions with or without a halo sign
    • Air crescent sign
    • Cavity
    • Wedge-shaped and segmental or lobar consolidation
  • Other pulmonary mold disease: as above, but also including a reverse halo sign
  • Tracheobronchitis: tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar seen on bronchoscopic analysis
  •  Sinonasal infection:
    •  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
• 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)
  • Tracheobronchitis
    • Aspergillus species on BAL or bronchial brush culture
    • Microscopy showing fungal elements on BAL or bronchial brush
  • Sinonasal disease
    • Mold on culture or microscopy of sinus aspirate
  • For Aspergillus species
    • Galactomannan in plasma, serum, BAL, or CSF
      • Serum or plasma ≥1
      • BAL ≥1
      • Serum or plasma ≥0.7 and BAL ≥0.8
      • CSF ≥1
    • PCR
      • Plasma, serum, or whole blood positive on 2 consecutive tests
      • BAL positive on 2 or more tests
      • At least 1 positive from plasma, serum, or whole blood and one positive from BAL

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