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Criteria for Proven Invasive Fungal Disease

Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies.

Criteria for Proven Invasive Fungal Disease

Fungus Characteristic
Moldsa Microscopic Analysis: Histopathologic, cytopathologic, or direct microscopic examinationb of a specimen obtained by needle aspiration or biopsy in which hyphae or melanized yeast-like forms are seen accompanied by evidence of associated tissue damage
Culture: Recovery of a hyaline or pigmented mold by culture of a specimen obtained by a sterile procedure from a normally sterile and clinically or radiologically abnormal site consistent with an infectious disease process, excluding BAL fluid, a paranasal or mastoid sinus cavity specimen, and urine
Blood: Blood culture that yields a moldc (eg, Fusarium species) in the context of a compatible infectious disease process
Serology: Not applicable
Tissue Nucleic Acid Diagnosis: Amplification of fungal DNA by PCR combined with DNA sequencing when molds are seen in formalin-fixed paraffin-embedded tissue
Yeastsa Microscopic Analysis: Histopathologic, cytopathologic, or direct microscopic examination of a specimen obtained by needle aspiration or biopsy from a normally sterile site (other than mucous membranes) showing yeast cells, for example, Cryptococcus species indicating encapsulated budding yeasts or Candida species showing pseudohyphae or true hyphaed
Culture: Recovery of a yeast by culture of a sample obtained by a sterile procedure (including a freshly placed [<24 hours ago] drain) from a normally sterile site showing a clinical or radiological abnormality consistent with an infectious disease process
Blood: Blood culture that yields yeast (eg, Cryptococcus or Candida species) or yeast-like fungi (eg, Trichosporon species)
Serology: Cryptococcal antigen in cerebrospinal fluid or blood confirms cryptococcosis
Tissue Nucleic Acid Diagnosis: Amplification of fungal DNA by PCR combined with DNA sequencing when yeasts are seen in formalin-fixed paraffin-embedded tissue
Pneumocystis Microscopic Analysis: Detection of the organism microscopically in tissue, BAL fluid, expectorated sputum using conventional or immunofluorescence staining
Culture: Not applicable
Blood: Not applicable
Serology: Not applicable
Tissue Nucleic Acid Diagnosis: Not applicable
Endemic mycoses Microscopic Analysis: Histopathology or direct microscopy of specimens obtained from an affected site showing the distinctive form of the fungus
Culture: Recovery by culture of the fungus from specimens from an affected site
Blood: Blood culture that yields the fungus
Serology: Not applicable
Tissue Nucleic Acid Diagnosis: Not applicable

Abbreviations: BAL, bronchoalveolar lavage; PCR, polymerase chain reaction.

a If culture is available, append the identification at the genus or species level from the culture results.
b Tissue and cells submitted for histopathologic or cytopathologic studies should be stained using Grocott-Gomori methenamine silver stain or periodic acid Schiff stain to facilitate inspection of fungal structures. Whenever possible, wet mounts of specimens from foci related to invasive fungal disease should be stained with a fluorescent dye (eg, calcofluor or blankophor).
c Recovery of Aspergillus species from blood cultures rarely indicates endovascular disease and almost always represents contamination
d Trichosporon and yeast-like Geotrichum species and Blastoschizomyces capitatus may also form pseudohyphae or true hyphae.

 

 

References:

  1. Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG. 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. Clin Infect Dis. 2020 Sep 12;71(6):1367-1376. [Medline]
  2. Cornely OA, Hoenigl M, Lass-Flörl C, Chen SC, Kontoyiannis DP, Morrissey CO, Thompson GR 3rd; Mycoses Study Group Education and Research Consortium (MSG-ERC) and the European Confederation of Medical Mycology (ECMM). Defining breakthrough invasive fungal infection-Position paper of the mycoses study group education and research consortium and the European Confederation of Medical Mycology. Mycoses. 2019 Sep;62(9):716-729. [Medline]

 

Created Apr 23, 2021.

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