Mucormycosis diagnostic criteria

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Syed Hassan A. Kazmi BSc, MD [2]

Diagnostic Criteria

Mucormycosis may be diagnosed using the definitions and criteria provided by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. It classifies invasive fungal infection as:

• Proven invasive fungal disease except endemic mycosis
• Probable invasive fungal disease except endemic mycosis
• Criteria for diagnosis of endemic mycosis

Criteria for proven invasive fungal disease except for endemic mycoses

Analysis and specimen	Molds	Yeasts
Microscopic analysis: sterile material	Histopathologic, cytopathologic, or direct microscopic examination 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	Histopathologic, cytopathologic, or direct microscopic examinationb 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 indicated by encapsulated budding yeasts or Candida species showing pseudohyphae or true hyphae
Sterile material	Recovery of a mold or “black yeast” 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 bronchoalveolar lavage fluid, a cranial sinus cavity specimen, and urine	Recovery of a yeast by culture of a sample obtained by a sterile procedure (including a freshly placed [<24 h ago] drain) from a normally sterile site showing a clinical or radiological abnormality consistent with an infectious disease process
Blood	Blood culture that yields a mold (e.g., Fusarium species) in the context of a compatible infectious disease process	Blood culture that yields yeast (e.g., Cryptococcus or Candida species) or yeast-like fungi (e.g., Trichosporon species)
Serological analysis: CSF	Not applicable	Cryptococcal antigen in CSF indicates disseminated cryptococcosis

Criteria for probable invasive fungal disease except for endemic mycoses

Host factors:

• Recent history of neutropenia (<0.5 × 109 neutrophils/L [<500 neutrophils/mm3] for >10 days) temporally related to the onset of fungal disease

• Receipt of an allogeneic stem cell transplant

• Prolonged use of corticosteroids (excluding among patients with allergic bronchopulmonary aspergillosis) 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 blockers, 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:
  1. Dense, well-circumscribed lesions(s) with or without a halo sign
  2. Air crescent sign
  3. Cavity

• Tracheobronchitis

• Tracheobronchial ulceration, nodule, pseudomembrane, plaque, or eschar seen on bronchoscopic analysis

• Sino-nasal infection

• Imaging showing sinusitis plus at least 1 of the following 3 signs:

1. Acute localized pain (including pain radiating to the eye)
2. Nasal ulcer with black eschar
3. Extension from the paranasal sinus across bony barriers, including into the orbit

• CNS infection

• 1 of the following 2 signs:

1. Focal lesions on imaging
2. 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:

1. Small, target-like abscesses (bull's-eye lesions) in liver or spleen
2. 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:

1. Presence of fungal elements indicating a mold
2. 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

Criteria for proven endemic mycosis

• In a host with an illness consistent with an endemic mycosis, 1 of the following:

1. Recovery in culture from a specimen obtained from the affected site or from blood
2. Histopathologic or direct microscopic demonstration of appropriate morphologic forms with a truly distinctive appearance characteristic of dimorphic fungi, such as Coccidioides species spherules, Blastomyces dermatitidis thick-walled broad-based budding yeasts, Paracoccidioides brasiliensis multiple budding yeast cells, and, in the case of histoplasmosis, the presence of characteristic intracellular yeast forms in a phagocyte in a peripheral blood smear or in tissue macrophages.

• For coccidioidomycosis, demonstration of coccidioidal antibody in CSF, or a 2-dilution rise measured in 2 consecutive blood samples tested concurrently in the setting of an ongoing infectious disease process
• For paracoccidioidomycosis, demonstration in 2 consecutive serum samples of a precipitin band to paracoccidioidin concurrently in the setting of an ongoing infectious disease process

Probable endemic mycosis

• Presence of a host factor, plus a clinical picture consistent with endemic mycosis and mycological evidence, such as a positive Histoplasma antigen test result from urine, blood, or CSF