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Objectives: We aimed to describe features and outcomes of cryptococcosis among HIV-seronegative individuals in a large surveillance network for cryptococcosis in France., Methods: We included incident cases of cryptococcosis in HIV-seronegative individuals from 2005 to 2020. We compared patient characteristics, disease presentations, cryptococcal antigen results, and induction antifungal treatments according to underlying disease. We examined factors associated with 90-day mortality. Among patients with disseminated infections, we investigated whether receipt of flucytosine and polyene combination was associated with lower mortality., Results: Among 652 individuals, 209 (32.1%) had malignancy, 130 (19.9%) were solid-organ transplant recipients, 204 (31.3%) had other immunocompromising conditions, and 109 (16.7%) had no reported underlying factor. The commonest presentations were disseminated infections (63.3%, 413/652) and isolated pulmonary infections (25.3%, 165/652). Solid-organ transplant patients were most likely to have disseminated infections and a positive serum cryptococcal antigen result. Patients with malignancy were older and less likely to receive a flucytosine-containing regimen for disseminated infections than others (58.7%, 78/133 vs. 73.2%, 194/265; p 0.029). The crude 90-day case-fatality ratio was 27.2% (95% CI, 23.5%-31.1%). Age ≥60 years (aOR: 2.75 [1.78-4.26]; p < 0.001), meningitis/fungaemia (aOR: 4.79 [1.80-12.7]; p 0.002), and malignancy (aOR: 2.4 [1.14-5.07]; p 0.02) were associated with higher 90-day mortality. Receipt of flucytosine and polyene combination was associated with lower 90-day mortality (aOR: 0.40 [0.23-0.71]; p 0.002) in multivariable analysis and inverse probability of treatment weighted analysis (aOR: 0.45 [0.25-0.80]; p 0.006)., Discussion: HIV-seronegative individuals with cryptococcosis comprise a wide range of underlying conditions with different presentations and outcomes, requiring a tailored approach to diagnosis and management., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To determine the epidemiological cut-off values (ECVs) of ten antifungal agents in a wide range of yeasts and Aspergillus spp. using gradient concentration strips., Methods: The minimum inhibitory concentrations for amphotericin B, anidulafungin, caspofungin, micafungin, flucytosine, fluconazole, itraconazole, isavuconazole, posaconazole, and voriconazole, determined with gradient concentration strips at 35 French microbiology laboratories between 2002 and 2020, were retrospectively collected. Then, the ECVs were calculated using the iterative method and a cut-off value of 97.5%., Results: Minimum inhibitory concentrations were available for 17 653 clinical isolates. In total, 48 ECVs (including 32 new ECVs) were determined: 29 ECVs for frequent yeast species (e.g. Candida albicans and itraconazole/flucytosine, and Candida glabrata species complex [SC] and flucytosine) and rare yeast species (e.g. Candida dubliniensis, Candida inconspicua, Saccharomyces cerevisiae, and Cryptococcus neoformans) and 19 ECVs for Aspergillusflavus SC, Aspergillusfumigatus SC, Aspergillusnidulans SC, Aspergillusniger SC, and Aspergillusterreus SC., Conclusions: These ECVs can be added to the already available gradient concentration strip-specific ECVs to facilitate minimum inhibitory concentration interpretation and streamline the identification of nonwild type isolates., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: Invasive aspergillosis is a threat for immunocompromised patients. We present a case series of aggressive cerebral vasculitis caused by Aspergillus spp. infection in immunocompromised patients., Methods: We present a retrospective case series of three autopsy-proven invasive cerebral aspergillosis with diffuse vasculitis affecting large caliber cerebral vessels., Results: Three patients were immunosuppressed: one on rituximab, one on corticosteroids, and one with a renal transplant. Two of these patients were diagnosed with cerebral aspergillosis on postmortem., Conclusion: Aspergillus cerebral vasculitis is a rare form of invasive aspergillosis that should be considered in an immunocompromised individual with suggestive lesions on imaging. It should be suspected as a possible cause of aseptic neutrophil meningitis., Competing Interests: Declaration of Competing Interest The authors declare they have no conflict of interests., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care., Methods: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221., Findings: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (>14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (<1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p<0·0001)., Interpretation: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19., Funding: Pfizer., Competing Interests: Declaration of interests J-PG reports personal fees from Gilead and grants and personal fees from Pfizer, outside of the submitted work. ED reports grants and non-financial support from Merck Sharp & Dohme and Gilead and non-financial support from Pfizer and Astellas, outside of the submitted work. AF reports personal fees and non-financial support from Merck Sharp & Dohme, grants from Janssen, personal fees and non-financial support from Gilead, and non-financial support from Pfizer, outside of the submitted work. C-EL reports personal fees from Carmat, Merck, BioMérieux, Brahms (part of Thermo Fisher Scientific), Bayer Healthcare, and Faron, outside of the submitted work. FraB reports grants from Astellas, personal fees from Merck Sharp & Dohme, and non-financial support from Pfizer, Merck Sharp & Dohme, and Astellas, outside of the submitted work. J-FT reports personal fees from Pfizer, Merck, Astellas, and Gilead, outside of the submitted work. FP reports non-financial support from Gilead and Pfizer, outside of the submitted work. EmC reports personal fees from Gilead, Baxter, and Sanofi-Genzyme, outside of the submitted work. AA reports personal fees from Pfizer and Gilead, outside of the submitted work. MC reports grants from Pfizer, outside of the submitted work. JuM reports non-financial support from Gilead, outside of the submitted work. SE reports grants, personal fees, and non-financial support from Aerogen and Fisher & Paykel, outside of the submitted work. GV reports grants and personal fees from BioMérieux and grants from SOS Oxygène and Janssen, outside of the submitted work. JeM reports grants from Pfizer and Gilead, outside of the submitted work. J-RZ reports grants and personal fees from Merck Sharp & Dohme and personal fees from Novartis and Pfizer, outside of the submitted work. M-EB reports grants from Pfizer during the conduct of the study; grants and non-financial support from Gilead and Pfizer, and non-financial support from Merck Sharp & Dohme, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)