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Background In this study we evaluated the incidence of invasive pulmonary aspergillosis among intubated patients with critical coronavirus disease 2019 (COVID-19) and evaluated different case definitions of invasive aspergillosis. Methods Prospective, multicentre study on adult patients with microbiologically confirmed COVID-19 receiving mechanical ventilation. All included participants underwent screening protocol for invasive pulmonary aspergillosis with bronchoalveolar lavage galactomannan and cultures performed on admission at 7 days and in case of clinical deterioration. Cases were classified as coronavirus associated pulmonary aspergillosis (CAPA) according to previous consensus definitions. The new definition was compared with putative invasive pulmonary aspergillosis (PIPA). Results A total of 108 patients were enrolled. Probable CAPA was diagnosed in 30 (27.7%) of patients after a median of 4 (2-8) days from intensive care unit (ICU) admission. Kaplan-Meier curves showed a significant higher 30-day mortality rate from ICU admission among patients with either CAPA (44% vs 19%, p= 0.002) or PIPA (74% vs 26%, p<0.001) when compared with patients not fulfilling criteria for aspergillosis. The association between CAPA [OR 3.53 (95%CI 1.29-9.67), P=0.014] or PIPA [OR 11.60 (95%CI 3.24-41.29) p<0.001] with 30-day mortality from ICU admission was confirmed even after adjustment for confounders with a logistic regression model. Among patients with CAPA receiving voriconazole treatment (13 patients, 43%) A trend toward lower mortality (46% vs 59% p=0.30) and reduction of galactomannan index in consecutive samples was observed. Conclusion We found a high incidence of CAPA among critically ill COVID-19 patients and that its occurrence seems to change the natural history of disease

Zygomycosis should be considered in immunosuppressed patients who develop sinusitis while receiving VRC prophylaxis, especially those with diabetes and malnutrition.

Because discriminating between zygomycosis and aspergillosis in a timely fashion is difficult, the pursuit of aggressive diagnostic strategies and prompt initiation of antifungal agents with activity against Zygomycetes should be considered for patients with hematological malignancy who are at an increased risk for zygomycosis.

Purpose: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung.

SUMMARY Rhizopus , Mucor , and Lichtheimia (formerly Absidia ) species are the most common members of the order Mucorales that cause mucormycosis, accounting for 70 to 80% of all cases. In contrast, Cunninghamella , Apophysomyces , Saksenaea , Rhizomucor , Cokeromyces , Actinomucor , and Syncephalastrum species individually are responsible for fewer than 1 to 5% of reported cases of mucormycosis. In this review, we provide an overview of the epidemiology, clinical manifestations, diagnosis of, treatment of, and prognosis for unusual Mucormycetes infections (non- Rhizopus , - Mucor , and - Lichtheimia species). The infections caused by these less frequent members of the order Mucorales frequently differ in their epidemiology, geographic distribution, and disease manifestations. Cunninghamella bertholletiae and Rhizomucor pusillus affect primarily immunocompromised hosts, mostly resulting from spore inhalation, causing pulmonary and disseminated infections with high mortality rates. R. pusillus infections are nosocomial or health care related in a large proportion of cases. While Apophysomyces elegans and Saksenaea vasiformis are occasionally responsible for infections in immunocompromised individuals, most cases are encountered in immunocompetent individuals as a result of trauma, leading to soft tissue infections with relatively low mortality rates. Increased knowledge of the epidemiology and clinical presentations of these unusual Mucormycetes infections may improve early diagnosis and treatment.

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Unlike invasive aspergillosis, the prognosis and outcome of hematologic malignancy patients who develop invasive mucormycosis have not significantly improved over the past decade as a majority of patients who develop the infection still die 12 weeks after diagnosis. However, early recognition and treatment of invasive mucormycosis syndromes, as well as individualized approaches to treatment and secondary prophylaxis, could improve the odds of survival, even in the most persistently immunosuppressed patient receiving chemotherapy and/or of stem cell transplantation. Herein, we describe the subtle clinical and radiographic clues that should alert the hematologist to the possibility of mucormycosis, and aggressive and timely treatment approaches that may limit the spread of infection before it becomes fatal. Hematology patients with this opportunistic infection require integrated care across several disciplines and frequently highly individualized and complex sequence of decision-making. We also offer perspectives for the use of 2 antifungals, amphotericin B products and posaconazole, with activity against Mucorales. The availability of posaconazole in an oral formulation that can be administered safely for prolonged periods makes it an attractive agent for long-term primary and secondary prophylaxis. However, serum drug concentration monitoring may be required to minimize breakthrough infection or relapsing mucormycosis associated with inadequate blood concentrations. (Blood. 2011;118(5):1216-1224) IntroductionMucormycosis is the unifying term used to describe infections caused by fungi belonging to the order Mucorales. Zygomycosis, an alternative term used to describe these life-threatening infections, has become less accurate based on a recent taxonomic reclassification (based on molecular identification) that abolished Zygomycetes as a class. [1][2][3][4] Rhizopus, Mucor, and Rhizomucor species account for up to 75% of mucormycosis cases encountered in hematologic malignancy patients. [5][6][7] Mucorales typically cause acute, aggressive, and frequently angioinvasive infections, especially in immunosuppressed hosts with hematologic malignancy and/or stem cell transplantation (SCT). 8,9 This opportunistic, geographically broad mycosis was highlighted as a sporadic cause of death in leukemia patients in the 1950s 10 until the mid 1990s where there has been an apparent increase in the documented cases in hematology units throughout the Westernized world ( Figure 1). [4][5][6][7]11 These cases are typically considered community-acquired, as nosocomial cases are less common in modern SCT and transplant units. 12 However, the true incidence of mucormycosis is not known and probably underestimated because of difficulties in antemortem diagnosis and the low autopsy rates in contemporary patients who die in the setting of leukemia or SCT. 13 The predisposing factors for mucormycosis in patients with hematologic cancer are similar to ones encountered in other opportunistic mold infections, such as aspergillosis, includi...