Invasive fungal infection: Difference between revisions

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(: updated probable infection to 2019 guidelines)
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== Classification (excluding endemic fungi) ==
 
== Classification (excluding endemic fungi) ==
  +
=== Probable invasive pulmonary mold disease ===
 
* The classification is based on a combination of patient risk factors (host factors), imaging, and mycology [[CiteRef::de pauw2008re]]
+
* 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 [[CiteRef:: donnelly2019re]]
 
* '''Host factors'''
 
* '''Host factors'''
 
** Recent history of '''neutropenia''' (<0.5 × 109 neutrophils/L for >10 days) temporally related to the onset of fungal disease
 
** 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'''
 
** 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
+
** 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 [[cyclosporine]], TNF-α inhibitors, specific monoclonal antibodies (such as [[alemtuzumab]]), or nucleoside analogues during the past 90 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]] or [[severe combined immunodeficiency]])
+
** '''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'''
 
* '''Clinical criteria'''
**'''Lower respiratory tract fungal disease''': the presence of 1 of the following 3 signs on CT
+
** '''Pulmonary aspergillosis''': any of the following patterns on CT
*** Dense, well-circumscribed lesions(s) with or without a halo sign
+
*** Dense, well-circumscribed lesions with or without a halo sign
*** Air-crescent sign
+
*** Air crescent sign
 
*** Cavity
 
*** 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
 
** '''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:
+
** '''Sinonasal infection''':
 
*** Acute localized pain (including pain radiating to the eye)
 
*** Acute localized pain (including pain radiating to the eye)
 
*** Nasal ulcer with black eschar
 
*** Nasal ulcer with black eschar
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*** Focal lesions on imaging
 
*** Focal lesions on imaging
 
*** Meningeal enhancement on MRI or CT
 
*** 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'''
 
* '''Mycological criteria'''
 
** '''Direct test''' (cytology, direct microscopy, or culture)
 
** '''Direct test''' (cytology, direct microscopy, or culture)
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*** Presence of fungal elements indicating a mold
 
*** Presence of fungal elements indicating a mold
 
*** Recovery by culture of a mold (e.g., Aspergillus, Fusarium, Zygomycetes, or Scedosporium species)
 
*** Recovery by culture of a mold (e.g., Aspergillus, Fusarium, Zygomycetes, or Scedosporium species)
  +
** '''Tracheobronchitis'''
** '''Indirect tests''' (detection of antigen or cell-wall constituents)
 
  +
*** [[Aspergillus species]] on BAL or bronchial brush culture
*** Aspergillosis: Galactomannan antigen detected in plasma, serum, bronchoalveolar lavage fluid, or CSF
 
  +
*** Microscopy showing fungal elements on BAL or bronchial brush
*** Invasive fungal disease other than cryptococcosis and zygomycoses: β-d-glucan detected in serum
 
  +
** 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 ===
 
=== Proven ===
 
 
* Fungal elements in biopsy of diseased tissue, or highly specific indirect assays
 
* Fungal elements in biopsy of diseased tissue, or highly specific indirect assays
 
* Includes:
 
* Includes:

Revision as of 11:32, 18 December 2019

Microbiology

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

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

References

  1. ^  Oliver A. Cornely, Johan Maertens, Drew J. Winston, John Perfect, Andrew J. Ullmann, Thomas J. Walsh, David Helfgott, Jerzy Holowiecki, Dick Stockelberg, Yeow-Tee Goh, Mario Petrini, Cathy Hardalo, Ramachandran Suresh, David Angulo-Gonzalez. Posaconazole vs. Fluconazole or Itraconazole Prophylaxis in Patients with Neutropenia. New England Journal of Medicine. 2007;356(4):348-359. doi:10.1056/nejmoa061094.
  2. ^  J Peter Donnelly, Sharon C Chen, Carol A Kauffman, William J Steinbach, John W Baddley, Paul E Verweij, Cornelius J Clancy, John R Wingard, Shawn R Lockhart, Andreas H Groll, Tania C Sorrell, Matteo Bassetti, Hamdi Akan, Barbara D Alexander, David Andes, Elie Azoulay, Ralf Bialek, Robert W Bradsher, Stephane Bretagne, Thierry Calandra, Angela M Caliendo, Elio Castagnola, Mario Cruciani, Manuel Cuenca-Estrella, Catherine F Decker, Sujal R Desai, Brian Fisher, Thomas Harrison, Claus Peter Heussel, Henrik E Jensen, Christopher C Kibbler, Dimitrios P Kontoyiannis, Bart-Jan Kullberg, Katrien Lagrou, Frédéric Lamoth, Thomas Lehrnbecher, Jurgen Loeffler, Olivier Lortholary, Johan Maertens, Oscar Marchetti, Kieren A Marr, Henry Masur, Jacques F Meis, C Orla Morrisey, Marcio Nucci, Luis Ostrosky-Zeichner, Livio Pagano, Thomas F Patterson, John R Perfect, Zdenek Racil, Emmanuel Roilides, Marcus Ruhnke, Cornelia Schaefer Prokop, Shmuel Shoham, Monica A Slavin, David A Stevens, George R Thompson, Jose A Vazquez, Claudio Viscoli, Thomas J Walsh, Adilia Warris, L Joseph Wheat, P Lewis White, Theoklis E Zaoutis, Peter G Pappas. Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clinical Infectious Diseases. 2019;71(6):1367-1376. doi:10.1093/cid/ciz1008.