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. Author manuscript; available in PMC: 2022 Dec 27.
Published in final edited form as: Mycoses. 2021 Apr 6;64(9):1002–1014. doi: 10.1111/myc.13274

TABLE 1.

IPA definitions12,27,49

Diagnostic criteria Revised EORTC/MSG criteria (2019)49 AspICU criteria27 Modified AspICU12
Host factors
  1. Recent history of neutropenia (<0.5 × 109 neutrophils/L for more than 10 days) that is temporally related to the onset of fungal disease.

  2. Haematological malignancy

  3. Receipt of an allogeneic stem cell transplant.

  4. Receipt of a solid organ transplant

  5. Prolonged use of corticosteroids (excluding among patients with allergic bronchopulmonary aspergillosis) at a therapeutic dose of ≥0.3 mg/kg corticosteroids for ≥3 weeks in the past 60 days

  6. Treatment with other recognised T-cell immunosuppressants, such as calcineurin inhibitors, tumour necrosis factor-a blockers, lymphocyte-specific monoclonal antibodies, immunosuppressive nucleoside analogues during the past 90 days

  7. Treatment with recognised B-cell immunosuppressants, such as Bruton’s tyrosine kinase inhibitors, eg ibrutinib

  8. Acute graft-versus-host disease grade III or IV involving the gut, lungs or liver that is refractory to first-line treatment with steroids

  9. Inherited severe immunodeficiency.

  1. Neutropenia (<0.5 × 109 neutrophils/L) preceding or at the time of ICU admission.

  2. Underlying haematological or oncological malignancy treated with cytotoxic agents.

  3. Glucocorticoid treatment (prednisone equivalent >20 mg/day)

  4. Congenital or acquired immunodeficiency

None
Clinical Data For tracheobronchitis, bronchoscopic findings with:
  1. Tracheobronchial ulceration

  2. Nodule

  3. Pseudomembrane

  4. Plaque

  5. Eschar

For sino-nasal diseases
  1. Acute localised pain (including pain radiating to the eye)

  2. Nasal ulcer with black eschar extension from the paranasal sinus across bony barriers, including into the orbit

One of the following signs or symptoms:
  1. Fever refractory to at least 3 days of appropriate antibiotic therapy.

  2. Recrudescent fever after a period of defervescence of at least 48 h while still on antibiotics and without other apparent cause.

  3. Dyspnoea.

  4. Haemoptysis.

  5. Pleural friction rub or pleuritic chest pain.

  6. Worsening respiratory insufficiency in spite of appropriate antibiotic therapy and ventilatory support.

One of the following signs or symptoms:
  1. Fever refractory to at least 3 days of appropriate antibiotic therapy.

  2. Recrudescent fever after a period of defervescence of at least 48 h while still on antibiotics and without other apparent cause.

  3. Dyspnoea.

  4. Haemoptysis.

  5. Pleural friction rub or chest pain.

  6. Worsening respiratory insufficiency in spite of appropriate antibiotic therapy and ventilatory support.

Radiological findings For LRT, patients must have subjected to at least one CT scan and must exhibit 1 of the following 4 signs:
  1. Dense, well-circumscribed lesion(s) with or without a halo sign.

  2. An air-crescent sign.

  3. A cavity.

  4. Wedge-shaped and segmental or lobar consolidation

For Central nervous system infection
  1. Of the following 2 signs: Focal lesions on imaging Meningeal enhancement on magnetic resonance imaging or CT

Any infiltrate or abnormal pulmonary imaging by portable chest XR or CT scan of the lungs. Any infiltrate or abnormal pulmonary imaging by portable chest XR or CT scan of the lungs.
Mycological findings
  1. Positive culture and/or microscopy result for Aspergillus from sputum, BAL, bronchial brush or aspirate

  2. Galactomannan antigen detected in plasma, serum, BALF or CSF with any 1 of the following:
    1. Single serum or plasma: ≥1.0
    2. BAL fluid: ≥1.0
    3. Single serum or plasma: >0.7 and BAL fluid ≥0.8
    4. CSF: ≥1.0
  3. Aspergillus PCR:
    1. Plasma, serum, or whole blood 2 or more consecutive PCR tests positive
    2. BAL fluid 2 or more duplicate PCR tests positive
    3. At least 1 PCR test positive in plasma, serum, or whole blood and 1 PCR test positive in BAL fluid
Aspergillus-positive lower respiratory tract specimen culture (= entry criterion)
In the absence of a host factor: Semiquantitative Aspergillus-positive culture of BALF (+ or ++), without bacterial growth together with a positive cytological smear showing branching hyphae.
One or more has to be present:
  1. Histopathology or direct microscopic evidence of dichotomous septate hyphae with positive culture for Aspergillus from tissue.

  2. A positive Aspergillus culture from a BALF.

  3. Galactomannan optical index on BALF ≥1.

  4. Galactomannan optical index on serum ≥0.5.

Categories Proven IFD: Histopathological, cytopathologic or direct microscopic evidence for Aspergillus spp. in a specimen obtained by needle aspiration or biopsy accompanied by evidence of associated tissue damage
OR
Recovery of Aspergillus spp. 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
OR
Amplification of fungal DNA by PCR combined with DNA sequencing when moulds are seen in formalin-fixed paraffin-embedded tissue
Probable IFD: Host factor +Clinical feature/Radiological findings +Mycological findings
Possible IFD: Host factor +Clinical feature/Radiological findings
Proven IPA: Identical to EORTC/MSG criteria
Putative IPA: Aspergillus-positive lower respiratory tract specimen culture + Clinical Data + Radiological Findings + Host Factors OR Semiquantititative Aspergillus-positive culture plus positive cytological smear
Respiratory Tract Colonisation: when ≥1 criterion necessary for a diagnosis of putative IPA is not met.
Proven IPA: Identical to EORTC/MSG criteria
Putative IPA: Clinical data + Radiological findings + Mycological findings
Respiratory Tract Colonisation: when ≥1 criterion necessary for a diagnosis of putative IPA is not met.

Note: Abbreviations: BAL, bronchoalveolar lavage; BALF, bronchoalveolar lavage fluid; CSF, cerebrospinal fluid; CT, computed tomography; DNA, deoxyribonucleic acid; EORTC:/MSG, European Organization for the Research and Treatment of Cancer/Mycoses Study Group; h, hours; ICU, intensive care unit; IFD, invasive fungal disease; IPA, invasive pulmonary aspergillosis; kg, kilogram; L, litre; LRT, lower respiratory tract; mg, milligram; PCR, polymerase chain reaction; spp, species; XR, X-ray.