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We present a challenging case of a patient admitted to an intensive care unit with influenza-associated pulmonary aspergillosis (IAPA). The clinical course was characterised by refractory fungal pneumonia and tracheobronchitis, suspected drug-induced liver injury due to triazole antifungals, and secondary bacterial infections with multidrug-resistant microorganisms, resulting in a fatal outcome despite the optimisation of antifungal treatment through therapeutic drug monitoring. This case underscores the complexity that clinicians face in managing critically ill patients with invasive fungal infections. [ABSTRACT FROM AUTHOR]

Critically ill COVID-19 patients can develop invasive pulmonary aspergillosis (CAPA). Considering the weaknesses of diagnostic tests/case definitions, as well as the results from autoptic studies, there is a debate on the real burden of aspergillosis in COVID-19 patients. We performed a retrospective observational study on mechanically ventilated critically ill COVID-19 patients in an intensive care unit (ICU). The primary objective was to determine the burden of CAPA by comparing clinical diagnosis (through case definitions/diagnostic algorithms) with autopsy results. Twenty patients out of 168 (11.9%) developed probable CAPA. Seven (35%) were females, and the median age was 66 [IQR 59–72] years. Thirteen CAPA patients (65%) died and, for six, an autopsy was performed providing a proven diagnosis in four cases. Histopathology findings suggest a focal pattern, rather than invasive and diffuse fungal disease, in the context of prominent viral pneumonia. In a cohort of mechanically ventilated patients with probable CAPA, by performing a high rate of complete autopsies, invasive aspergillosis was not always proven. It is still not clear whether aspergillosis is the major driver of mortality in patients with CAPA. [ABSTRACT FROM AUTHOR]

Invasive fungal infections (IFIs) can complicate the clinical course of COVID-19 and are associated with a significant increase in mortality, especially in critically ill patients admitted to an intensive care unit (ICU). This narrative review concerns 4099 cases of IFIs in 58,784 COVID-19 patients involved in 168 studies. COVID-19-associated invasive pulmonary aspergillosis (CAPA) is a diagnostic challenge because its non-specific clinical/imaging features and the fact that the proposed clinically diagnostic algorithms do not really apply to COVID-19 patients. Forty-seven observational studies and 41 case reports have described a total of 478 CAPA cases that were mainly diagnosed on the basis of cultured respiratory specimens and/or biomarkers/molecular biology, usually without histopathological confirmation. Candidemia is a widely described secondary infection in critically ill patients undergoing prolonged hospitalisation, and the case reports and observational studies of 401 cases indicate high crude mortality rates of 56.1% and 74.8%, respectively. COVID-19 patients are often characterised by the presence of known risk factors for candidemia such as in-dwelling vascular catheters, mechanical ventilation, and broad-spectrum antibiotics. We also describe 3185 cases of mucormycosis (including 1549 cases of rhino-orbital mucormycosis (48.6%)), for which the main risk factor is a history of poorly controlled diabetes mellitus (>76%). Its diagnosis involves a histopathological examination of tissue biopsies, and its treatment requires anti-fungal therapy combined with aggressive surgical resection/debridement, but crude mortality rates are again high: 50.8% in case reports and 16% in observational studies. The presence of other secondary IFIs usually diagnosed in severely immunocompromised patients show that SARS-CoV-2 is capable of stunning the host immune system: 20 cases of Pneumocystis jirovecii pneumonia, 5 cases of cryptococcosis, 4 cases of histoplasmosis, 1 case of coccidioides infection, 1 case of pulmonary infection due to Fusarium spp., and 1 case of pulmonary infection due to Scedosporium. [ABSTRACT FROM AUTHOR]

Human histoplasmosis is a mycosis caused by two distinct varieties of a dimorphic fungus: Histoplasma capsulatum var. capsulatum and H. capsulatum var. duboisii. In Europe, it is usually imported by migrants and travellers, although there have been some autochthonous cases, especially in Italy; however, most European physicians are unfamiliar with its clinical and pathological picture, particularly among immunocompromised patients without HIV infection. This systematic review of all the cases of histoplasmosis reported in Europe and Israel between 2005 and 2020 identified 728 cases diagnosed in 17 European countries and Israel described in 133 articles. The vast majority were imported (mainly from Central and South America), but there were also seven autochthonous cases (six in Europe and one in Israel). The patients were prevalently males (60.4%), and their ages ranged from 2 to 86 years. The time between leaving an endemic region and the diagnosis of histoplasmosis varied from a few weeks to more than 40 years. Progressive disseminated histoplasmosis was the most frequent clinical picture among people living with HIV infection (89.5%) or a different immunocompromising condition (57.1%), but it was also recorded in 6.2% of immunocompetent patients. Twenty-eight cases were caused by Histoplasma duboisii. Immunocompromised patients without HIV infection had the worst outcomes, with a mortality rate of 32%. [ABSTRACT FROM AUTHOR]