Invasive Pulmonary Aspergillosis

Abstract

Invasive pulmonary aspergillosis is growing in incidence, as patients at risk are growing in diversity. Outside the classical context of neutropenia, new risk factors are emerging or newly identified, such as new anticancer drugs, viral pneumonias and hepatic dysfunctions. Clinical signs remain unspecific in these populations and the diagnostic work-up has considerably expanded. Computed tomography is key to assess the pulmonary lesions of aspergillosis, whose various features must be acknowledged. Positron-emission tomography can bring additional information for diagnosis and follow-up. The mycological argument for diagnosis is rarely fully conclusive, as biopsy from a sterile site is challenging in most clinical contexts. In patients with a risk and suggestive radiological findings, probable invasive aspergillosis is diagnosed through blood and bronchoalveolar lavage fluid samples by detecting galactomannan or DNA, or by direct microscopy and culture for the latter. Diagnosis is considered possible with mold infection in lack of mycological criterion. Nevertheless, the therapeutic decision should not be hindered by these research-oriented categories, that have been completed by better adapted ones in specific settings. Survival has been improved over the past decades with the development of relevant antifungals, including lipid formulations of amphotericin B and new azoles. New antifungals, including first-in-class molecules, are awaited.

Keywords: galactomannan; hematopoietic stem cell transplantation; isavuconazole; leukemia; liposomal amphotericin B; neutropenia; posaconazole; review; solid organ transplantation; voriconazole.

Figure 1

Invasive aspergillosis in a refractory acute myeloblastic leukemia patient. (A) CT-scan at diagnosis, showing a nodule surrounded by a halo. (B) CT-scan 4 weeks later, showing a small cavity.

Figure 2

Invasive aspergillosis in a non-neutropenic patient treated for B-cell lymphoma with alemtuzumab and dexamethasone, in a context of PCR-positive influenza A. (A) Differential diagnosis is difficult between viral or fungal infection for this tree-in-bud pattern. (B) Evolution observed on CT-scan 2 weeks later is characterized by increased size of nodules and pleural effusion. Invasive aspergillosis was eventually documented by repeated detection of galactomannan in serum and galactomannan, as well as septate hyphae, in bronchoalveolar lavage fluid.

Figure 5

Recommendations from the IDSA, ECIL and ESCMID for prophylaxis of invasive aspergillosis [21,99,128]. Abbreviations: IDSA: Infectious Disease Society of America; ECIL: European Conference on Infections in Leukemia; ESCMID: European Society of Clinical Microbiology and Infectious Diseases; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; alloSCT: allogeneic stem cell transplantation; GVHD: graft vs. host disease. * Fluconazole should be added for coverage of yeast infections in case aerosolized liposomal amphotericin B is used as an anti-mold prophylaxis. Antifungals are written in bold font when the recommendation is first choice, based on strong-quality evidence.

Figure 6

Recommendations from the IDSA, ECIL and ESCMID for targeted treatment of IA [99,128,148]. Abbreviations: IDSA: Infectious Disease Society of America; ECIL: European Conference on Infections in Leukemia; ESCMID: European Society of Clinical Microbiology and Infectious Diseases; AML: acute myeloid leukemia; MDS: myelodysplastic syndrome; alloSCT: allogeneic stem cell transplantation; GVHD: graft vs. host disease. Antifungals are written in bold font when the recommendation is first choice, based on strong-quality evidence.

Figure 3

Positron-emission tomography coupled with CT-scan in invasive aspergillosis in a solid organ transplant patient. Primary localization is pulmonary with an extent to chest wall. Dissemination to multiple organs including heart and soft tissue were diagnosed on PET-CT.

Figure 4

Invasive pulmonary aspergillosis diagnostic criteria [144,145,146]. Abbreviations: EORTC-MSG: European Organization for Research and Treatment of Cancer/Mycosis Study Group; AspICU: Aspergillosis in Intensive Care Unit diagnostic algorithm; BM-AspICU: Biomarkers-based Aspergillosis in Intensive Care Unit diagnostic algorithm; AlloSCT: allogeneic stem cell transplantation; aGVHD: acute graft vs. host disease; GM: galactomannan; PCR: polymerase chain reaction; BALF: bronchoalveolar lavage fluid, IA: invasive aspergillosis; IMD: invasive mold infection. EORTC-MSG 2020 mycological criterion consists of. -Direct microscopy or culture positive in sputum, bronchoalveolar lavage fluid (BALF), bronchial brush or aspirate, or. -GM index >1 in blood sample or >1 in BALF or >0.7 in blood sample and >0.8 in BALF, or. -PCR positive twice in blood or twice in BALF or once both in blood and BALF. BM-AspICU mycological criterion consists of positive culture in BALF, or positive GM or PCR in blood or BALF.