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]

Overview

An established criteria exists which can help in diagnosing mucormycosis. The criteria is 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 is based on microscopic findings, clinical criteria and characteristics of the fungus.

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	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 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 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