Diagnosis and treatment of invasive pulmonary aspergillosis in critically ill intensive care patients: executive summary of the German national guideline (AWMF 113-005)

Abstract

Purpose: The executive summary of the guideline aims to provide the most relevant recommendations on the diagnosis and treatment of invasive pulmonary aspergillosis in critically ill patients in the intensive care unit.

Methods: The guideline's work included a systematic literature search, selection and assessment of the data relevant to the issues identified. Key questions included the areas of epidemiology, risk factors, diagnostics, and therapy. They were discussed analogous to a PICO scheme within the guideline committee, with subsequent working groups proposing recommendations for specific key questions, which were then again discussed and finalized by the entire guideline committee.

Results: In addition to the classic risk factors (persistent neutropenia, allogeneic stem cell transplantation, congenital or acquired immunodeficiency, etc.), decompensated liver cirrhosis, COPD, solid tumours and viral pneumonia (influenza, COVID-19) have been established as risk factors for critically ill patients in need of intensive care. If there is no adequate improvement or even further clinical deterioration of the respiratory status in critically ill patients, the presence of IPA should be considered and appropriate diagnostic tests should be initiated. Diagnostics should include a CT scan of the chest and a broncho-alveolar lavage with culture for moulds, testing for galactomannan and PCR. Isavuconazole and voriconazole are recommended as first-line treatment, liposomal amphotericin B as an alternative, with posaconazole (PCZ) or the echinocandins (as an add-on to azole or polyene treatment) being additional options for salvage treatment.

Conclusion: Invasive aspergillosis in critically ill patients represents a diagnostic and therapeutic challenge. If indicated, invasive aspergillosis should be considered and appropriate diagnostic tests initiated. Isavuconazole and voriconazole are recommended as first-line treatment, liposomal amphotericin B as an alternative.

Keywords: Azoles; Critically ill patients; Drug interactions; Guideline; Intensive care medicine; Invasive pulmonary aspergillosis.

Fig. 1

Diagnostic and therapeutic algorithm for invasive (pulmonary) aspergillosis. ¹ Classic risk factors (e.g. allogeneic stem cell transplantation) are covered by the established EORTC/MSG definition [7]. ² oligosymptomatic course possible, especially in isolated TBA. ³ not in isolated TBA. ⁴ in isolated TBA, galactomannan and culture from bronchoalveolar lavage may be negative, in which case diagnosis from tracheal aspiration/bronchial lavage is recommended. ⁵ BALF highly preferred over serum. IPA invasive aspergillosis, BALF bronchoalveolar lavage fluid, COPD chronic obstructive pulmonary disease, COVID-19 coronavirus disease 2019, CT computed tomography, HIV human immunodeficiency virus, ICU intensive care unit, IPA invasive pulmonary aspergillosis, ODI optical density index, TBA tracheobronchial aspergillosis, ISA isavuconazole, VCZ voriconazole, LAmB liposomal amphotericin B. Due to the lack of standardization, the consensus recommendation [1] does not yet generally favor NAT for diagnostics. However, in experienced centers, it can be helpful in identifying species and resistance markers.