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When Candida dubliniensis isolates obtained from seabird excrement and from humans in Ireland were compared by using multilocus sequence typing, 13 of 14 avian isolates were genetically distinct from human isolates. The remaining avian isolate was indistinguishable from a human isolate, suggesting that transmission may occur between humans and birds. [ABSTRACT FROM AUTHOR]

Acute renal failure is frequent in HIV-infected patients and may be related to HIV-associated nephropathy, drugs, or opportunistic infections. We report a peculiar case of disseminated cryptococcosis complicated by acute renal failure associated with obstruction of intrarenal capillaries by Cryptococus neoformans dead bodies and successfully treated with plasma exchanges. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Background: Thirteen clustered cases of American histoplasmosis, a deep mycosis caused by Histoplasma capsulatum and acquired through inhalation of airborne spores was reported. Twenty-five persons traveled in Martinique, French West Indies. Thirteen underwent trekking and passed through a mountain tunnel full of bats (tunnel group). The 12 others performed canyoning and did not go through the tunnel (control group). Fifteen days after exposure, 1 patient of the tunnel group developed fever, chills, and cough.Methods: The index case was diagnosed in the hospital, but 12 cases where initially diagnosed as prolonged influenza. All individuals were contacted and submitted to a phone questionnaire. They were asked about eventual occurrence of influenzalike symptoms, about activities practiced, and the notion of contact with bats. All were invited to have clinical examinations, chest x-ray films, and blood samplings. Serologic testing for histoplasmosis was performed by immunodiffusion. Clinical evidence of infection with H. capsulatum was obtained in all the remaining patients of the tunnel group and in none in the control group. Symptoms occurred with an acute onset in 11 to 23 days: fever and chills, severe asthenia, headaches, digestive tract involvement, and then cough, dyspnea, hepatic involvement. Pulmonary micro- or macronodules and mediastinal adenopathies were seen on radiograph and/or computed tomography scan.Results: H. capsulatum serologic tests were positive in all 13 cases with presence of specific M and or H precipitins, 5 to 13 weeks after exposure, and were negative in control group. All patients were treated with itraconazole 200 mg per day during at least 2 months. Treatment was well tolerated; patients progressively recovered. Clinical and serologic follow-up was obtained for some patients at 1 and 4 years. The present study reports the first large outbreak of histoplasmosis acquired in Martinique.Conclusion: Histoplasmosis still occurs and is potentially serious. In patients returning from endemic areas, presenting prolonged influenzalike symptoms, clinicians should look for previous possible exposure to Histoplasma. [ABSTRACT FROM AUTHOR]

This study investigates the diagnostic practices for mucormycosis among 30 French University Hospital mycology laboratories, in 2024. All laboratories perform both direct examination and culture, with fluorescent brighteners being the most commonly used method for direct examination. While 77 % of the participating laboratories routinely identify Mucorales to the species level, with 70 % having adopted Mucorales-specific quantitative PCR, primarily for the diagnosis of invasive fungal infections. Antifungal susceptibility testing practices varied between centers, with 36.7 % of laboratories consistently performing these tests, primarily using gradient concentration strips. Amphotericin B, posaconazole, and isavuconazole were the most frequently tested antifungals. These findings highlight variations in laboratory practices and emphasize the importance of establishing uniform diagnostic and susceptibility testing methods to optimize mucormycosis management., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Eric Dannaoui has received research grants from Biomérieux: travel grants from Gilead, Mundipharma, and Pfizer; speaker's fee from Mundipharma, Pfizer, and Gilead. Kévin Brunet has received travel grants from Pfizer and Gilead and speaker's fee from Gilead. Laurence Millon has received travel grants from Gilead and Pfizer; speaker's fee from Gilead and Pfizer. Marjorie Cornu received travel grants and speaker's fee from Gilead and Pfizer. The other authors have no conflicts of interest to disclose., (Copyright © 2024 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Candida blankii is a recently reported yeast causing rare cases of fungemia. This species presents high minimum inhibitory concentrations (MICs) to fluconazole and echinocandins. We report an atypical C. blankii metacarpophalangeal osteo-articular infection in a patient with Chronic Granulomatous Disease. The patient was initially treated by a combination of voriconazole and 5-fluorocytosine (5-FC). However, the treatment was subsequently changed to posaconazole and then to a combination of caspofungin and 5-FC. 2012 Elsevier Ltd. All rights reserved., (© 2024 The Authors.)

Due to large outbreaks observed worldwide, Candida auris has emerged as a major threat to healthcare facilities. To prevent these phenomena, a systematic screening should be performed in patients transferred from regions where the pathogen is highly endemic. In this study, we recorded and analyzed French mycologists' current knowledge and practice regarding C. auris screening and diagnosis. Thirty-six centers answered an online questionnaire. Only 11 (30.6 %) participants were aware of any systematic screening for C. auris for patients admitted to their hospital. In the case of post-admission screening, axillae/groins (n = 21), nares (n = 7), rectum (n = 9), and mouth (n = 6) alone or various combinations were the body sites the most frequently sampled. Only six centers (8.3 %) reported using a commercially available plate allowing the differentiation of C. auris colonies from that of other Candida species, while five laboratories (13.8 %) had implemented a C. auris-specific qPCR. Considering the potential impact on infected patients and the risk of disorganization in the care of patients, it is crucial to remember to biologists and clinicians the utmost importance of systematic screening on admission., Competing Interests: Declaration of competing interest The authors declared no conflict of interest, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Mucormycosis is a deadly invasive fungal infection recently included in the WHO priority pathogen list. Here we sought to describe epidemiological trends of mucormycosis in France, and to evaluate factors associated with mortality., Methods: From 2012 to 2022, we implemented a nationwide prospective surveillance programme for mucormycosis in France, focusing on epidemiology, species, seasonal variations. Factors associated with 3-month mortality were studied by univariable and multivariable logistic regression., Findings: Among 550 cases of mucormycosis, the main underlying conditions were haematological malignancy (HM, 65.1%, 358/550), trauma (8%, 44/550), diabetes (7.5%, 41/550) and solid-organ transplants (6.5%, 36/550). Site of infection was pulmonary in 52.4% (288/550), rhinocerebral in 14.5% (80/550), and cutaneo-articular in 17.1% (94/550). Main species identified were Rhizopus arrhizus (21%, 67/316), Rhizopus microsporus (13.6%, 43/316), Lichtheimia corymbifera and Mucor circinelloides (13.3%, 42/316 each), Rhizomucor pusillus (12%, 38/316), and  Lichtheimia ramosa (10.8%, 34/316). We found associations between underlying condition, site of infection, and infecting species, including a previously undescribed triad of trauma, cutaneo-articular localisations, and L. ramosa / M. circinelloides . Diagnostic contribution of Polymerase Chain Reaction (PCR) increased from 16% (4/25) in 2012 to 91% (61/67) in 2022, with more than 50% of diagnoses relying solely on PCR in 2022. We also found seasonal variations with relatively more cases in autumn. Ninety-day mortality was 55.8% (276/495). Independent prognostic factors were age, diagnosis in Intensive Care Unit (ICU), and HM while diagnosis after 2015 (i.e. large implementation of PCR) and surgery were associated with reduced mortality., Interpretation: This study reveals major mucormycosis epidemiological changes in France, with a large predominance of HM patients, and a parallel between PCR multicentre implementation and improved prognosis. We also evidence new associations between species, localisations and risk factors, as well as seasonal variations., Funding: Recurrent financial support from Santé Publique France and Institut Pasteur., Competing Interests: SC reports travel grants for congresses for Gilead and Pfizer. GD reports being a speaker for Gilead. LM reports personal travel grants for Gilead and Pfizer. FL reports being a speaker for MSD and F2G board. AA reports educational lecture and travel grant from Gilead. Other authors declare no competing interests., (© 2024 The Author(s).)

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.)

Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease--related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.

Invasive fungal infections have recently been recognized by the WHO as a major health, epidemiological, and economic issue. Their high mortality rates and the emergence of drug resistance have driven the development of new molecules, including olorofim, an antifungal belonging to a new family of compounds, the orotomides. A review was conducted on the PubMed database and the ClinicalTrials.gov website to summarize the microbiological profile of olorofim and its role in the treatment of filamentous fungal infections. Twenty-four articles were included from the search and divided into two groups: an "in vitro" group focusing on minimum inhibitory concentration (MIC) results for various fungi and an "in vivo" group evaluating the pharmacokinetics (PK), pharmacodynamics (PD), efficacy, and tolerability of olorofim in animal models of fungal infection and in humans. Olorofim demonstrated in vitro and in vivo activity against numerous filamentous fungi, including azole-resistant Aspergillus fumigatus , various dermatophytes, and endemic and dimorphic fungi. in vitro results showed higher MICs for certain Fusarium species and dematiaceous fungi Alternaria alternata and Exophiala dermatitidis ; further in vivo studies are needed. Published PK-PD data in humans are limited. The results of the ongoing phase III clinical trial are eagerly awaited to evaluate olorofim's clinical impact.

Candida albicans chronically colonizes the respiratory tract of patients with Cystic Fibrosis (CF). It competes with CF-associated pathogens (e.g. Pseudomonas aeruginosa) and contributes to disease severity. We hypothesize that C. albicans undergoes specific adaptation mechanisms that explain its persistence in the CF lung environment. To identify the underlying genetic and phenotypic determinants, we serially recovered 146 C. albicans clinical isolates over a period of 30 months from the sputum of 25 antifungal-naive CF patients. Multilocus sequence typing analyses revealed that most patients were individually colonized with genetically close strains, facilitating comparative analyses between serial isolates. We strikingly observed differential ability to filament and form monospecies and dual-species biofilms with P. aeruginosa among 18 serial isolates sharing the same diploid sequence type, recovered within one year from a pediatric patient. Whole genome sequencing revealed that their genomes were highly heterozygous and similar to each other, displaying a highly clonal subpopulation structure. Data mining identified 34 non-synonymous heterozygous SNPs in 19 open reading frames differentiating the hyperfilamentous and strong biofilm-former strains from the remaining isolates. Among these, we detected a glycine-to-glutamate substitution at position 299 (G299E) in the deduced amino acid sequence of the zinc cluster transcription factor ROB1 (ROB1G299E), encoding a major regulator of filamentous growth and biofilm formation. Introduction of the G299E heterozygous mutation in a co-isolated weak biofilm-former CF strain was sufficient to confer hyperfilamentous growth, increased expression of hyphal-specific genes, increased monospecies biofilm formation and increased survival in dual-species biofilms formed with P. aeruginosa, indicating that ROB1G299E is a gain-of-function mutation. Disruption of ROB1 in a hyperfilamentous isolate carrying the ROB1G299E allele abolished hyperfilamentation and biofilm formation. Our study links a single heterozygous mutation to the ability of C. albicans to better survive during the interaction with other CF-associated microbes and illuminates how adaptive traits emerge in microbial pathogens to persistently colonize and/or infect the CF-patient airways., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Gnaien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience., Results: While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools., Conclusions: In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon. Video Abstract., (© 2024. The Author(s).)

The opportunistic fungal pathogen Candida albicans damages host cells via its peptide toxin, candidalysin. Before secretion, candidalysin is embedded in a precursor protein, Ece1, which consists of a signal peptide, the precursor of candidalysin and seven non-candidalysin Ece1 peptides (NCEPs), and is found to be conserved in clinical isolates. Here we show that the Ece1 polyprotein does not resemble the usual precursor structure of peptide toxins. C. albicans cells are not susceptible to their own toxin, and single NCEPs adjacent to candidalysin are sufficient to prevent host cell toxicity. Using a series of Ece1 mutants, mass spectrometry and anti-candidalysin nanobodies, we show that NCEPs play a role in intracellular Ece1 folding and candidalysin secretion. Removal of single NCEPs or modifications of peptide sequences cause an unfolded protein response (UPR), which in turn inhibits hypha formation and pathogenicity in vitro. Our data indicate that the Ece1 precursor is not required to block premature pore-forming toxicity, but rather to prevent intracellular auto-aggregation of candidalysin sequences., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n = 8), hyalohyphomycetes (n = 3), dermatophytes (n = 1), and mucorale (n = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Immunocompromised patients now represent the population most at risk for severe coronavirus disease 2019. Persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding was reported in these patients ranging from several weeks up to 9 months. We conducted a bicentric retrospective case-control study to identify risk and prognostic factors associated with persistent viral shedding in immunocompromised patients., Material and Methods: Symptomatic immunocompromised adults with persistent SARS-CoV-2 viral shedding >8 weeks were retrospectively included between 1 March 2020 and 24 April 2022 at 2 university hospitals in Paris, France, and matched with a control group consisting of symptomatic immunocompromised patients without persistent viral shedding., Results: Twenty-nine immunocompromised patients with persistent viral shedding were compared with 40 controls. In multivariate analysis, fever and lymphocytopenia (<0.5 G/L) were associated with an increased risk of persistent viral shedding (odds ratio [OR]: 3.3; 95% confidence interval [CI], 1.01-11.09) P = .048 and OR: 4.3; 95% CI, 1.2-14.7; P = .019, respectively). Unvaccinated patients had a 6-fold increased risk of persistent viral shedding (OR, 6.6; 95% CI, 1.7-25.1; P = .006). Patients with persistent viral shedding were at risk of hospitalization (OR: 4.8; 95 CI, 1.5-15.6; P = .008), invasive aspergillosis (OR: 10.17; 95 CI, 1.15-89.8; P = .037) and death (log-rank test <0.01)., Conclusions: Vaccine coverage was protective against SARS-CoV-2 persistent viral shedding in immunocompromised patients. This new group of immunocompromised patients with SARS-CoV-2 persistent viral shedding is at risk of developing invasive aspergillosis and death and should therefore be systematically screened for this fungal infection for as long as the viral shedding persists., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

The Candida albicans population displays high genetic diversity illustrated by 18-well differentiated genetic clusters. Cluster 13, also known as Candida africana, is an outlying cluster and includes strains first described as atypical C. albicans isolates of vaginal origin, showing apparent tropism for the female genital tract. In our study, we combined in vitro, and in vivo models to explore the colonization and pathogenic potential of C. africana. We report that C. africana has similar fitness to C. albicans when it comes to colonization of the oral and vaginal mucosa, however it has decreased fitness in gastro-intestinal colonization and systemic infection. Interestingly, despite high population homogeneity, our in vitro data highlighted for the first time a variability in terms of growth rate, biofilm formation and filamentation properties between C. africana strains. Overall, our data lays the foundations for exploring specific features of C. africana that might contribute to its apparent niche restriction., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Among 1107 cryptococcosis cases from the French surveillance network (2005-2020), the proportion of HIV-seronegative individuals has recently surpassed that of HIV-seropositive individuals. We observed marked differences in patient characteristics, disease presentations, cryptococcal antigen results, infecting species, and mortality according to HIV serostatus., Competing Interests: Potential conflicts of interest. Over the past 5 years, E. D. has received research grants from MSD, Gilead, and bioMérieux; travel grants from Gilead, MSD, and Pfizer; and speaker's fees from Gilead and Pfizer. All other authors report no potential conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

In silico and experimental approaches have allowed an ever-growing understanding of the interactions within the microbiota. For instance, recently acquired data have increased knowledge of the mechanisms that support, in the gut and vaginal microbiota, the resistance to colonization by Candida albicans, an opportunistic fungal pathogen whose overgrowth can initiate severe infections in immunocompromised patients. Here, we review how bacteria from the microbiota interact with C. albicans. We show how recent OMICs-based pipelines, using metagenomics and/or metabolomics, have identified bacterial species and metabolites modulating C. albicans growth. We finally discuss how the combined use of cutting-edge OMICs-based and experimental approaches could provide new means to control C. albicans overgrowth within the microbiota and prevent its consequences., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Intestinal microsporidiosis is most often caused by Enterocytozoon bieneusi , and to a lesser extent by species of the genus Encephalitozoon . Until now, Encephalitozoon hellem was not clearly known to induce disease restricted to the intestine, or rarely in HIV subjects or in tropical countries. We report here 11 cases of delineated intestinal microsporidioses due to E. hellem diagnosed in France in non-HIV patients. Briefly, all patients were immunocompromised. They all suffered from diarrhoea, associated in nearly 50% of cases with weight loss. Concerning treatment, 5/11 patients had a discontinuation or a decrease of their immunosuppressive therapy, and 4/11 received albendazole. All patients recovered. Five different genotypes were identified based on the rRNA ITS sequence.

Candida albicans is a commensal yeast present in the gut of most healthy individuals but with highly variable concentrations. However, little is known about the host factors that influence colonization densities. We investigated how microbiota, host lifestyle factors, and genetics could shape C. albicans intestinal carriage in 695 healthy individuals from the Milieu Intérieur cohort. C. albicans intestinal carriage was detected in 82.9% of the subjects using quantitative PCR. Using linear mixed models and multiway-ANOVA, we explored C. albicans intestinal levels with regard to gut microbiota composition and lifestyle factors including diet. By analyzing shotgun metagenomics data and C. albicans qPCR data, we showed that Intestinimonas butyriciproducens was the only gut microbiota species whose relative abundance was negatively correlated with C. albicans concentration. Diet is also linked to C. albicans growth, with eating between meals and a low-sodium diet being associated with higher C. albicans levels. Furthermore, by Genome-Wide Association Study, we identified 26 single nucleotide polymorphisms suggestively associated with C. albicans colonization. In addition, we found that the intestinal levels of C. albicans might influence the host immune response, specifically in response to fungal challenge. We analyzed the transcriptional levels of 546 immune genes and the concentration of 13 cytokines after whole blood stimulation with C. albicans cells and showed positive associations between the extent of C. albicans intestinal levels and NLRP3 expression, as well as secreted IL-2 and CXCL5 concentrations. Taken together, these findings open the way for potential new interventional strategies to curb C. albicans intestinal overgrowth.

Background: Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality., Research Question: Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition?, Study Design and Methods: All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally., Results: A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01)., Interpretation: Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. Coste has received a travel grant from the association Marie-Bertille. O. L. has received speaker's fees from MSD, Gilead, Astellas, Pfizer, and F2G, and is consultant for Gilead. F. L. has received personal fees from Gilead, F2G and Pfizer. R. H. has received a grant from Gilead and personal honoraria from Pfizer, Gilead, and Mundipharma. L. M. has received travel grants from Gilead and Pfizer. F. D. has received personal fees from Gilead, outside the submitted work. None declared (A. Conrad, R. P., S. P., P. P., C. D., V. L.-B., F. M., T. G., M.-E. B., F. S., G. N., D. D., F. A., C. H.-D., S. D.-L., F. B., G. G., S. A., D. B., M.-P. L., J.-E. H., C. R., G. M., E. B., O. P., D. G.-H.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Objectives: We aimed to describe patients with autoimmune diseases (AID) developing invasive fungal disease (IFD) and identify factors associated with short-term mortality., Methods: We analysed cases of IFD associated with AID from the surveillance network of invasive fungal diseases (Réseau de surveillance des infections fongiques invasives, RESSIF) registry of the French national reference centre for invasive mycoses. We studied association of AID-specific treatments with 30-day mortality. We analysed total lymphocyte and CD4-T cell counts in patients with Pneumocystis jirovecii pneumonia (PCP)., Results: From 2012 to 2018, 549 individuals with IFD and AID were included, mainly with PCP (n=227, 41.3%), fungemia (n=167, 30.4%) and invasive aspergillosis (n=84, 15.5%). Rheumatoid arthritis (RA) and anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) were the most frequent AID in PCP (n=55 and 25, respectively) and invasive aspergillosis (n=15 and 10, respectively), inflammatory bowel diseases (IBDs) were predominant in fungemia (n=36). At IFD diagnosis, 365 (66.5%) patients received glucocorticoids (GCs), 285 (51.9%) immunosuppressants, 42 (7.7%) tumor necrosis factor (TNF)-α blockers, 75 (13.7%) other biologics. Mortality at 30 days was 28.1% (143/508). Fungemia and high-dose GCs were independently associated with higher 30-day mortality. In PCP patients, lymphopenia <1500/mm 3 was frequent (132/179, 73.7%) even if CD4+T cell count exceeded 200/mm 3 in 56/78 patients (71.8%) (median 472.5/mm 3 , IQR 160-858)., Conclusion: IFD associated with AID occurs primarily in RA, AAV and IBD, especially when treated with GCs and immunosuppressants. Mortality is high, especially for patients on high-dose GCs. Lymphopenia may help identify risk of PCP, but normal CD4+T cell count does not rule out the risk. Further studies are needed to assess the individual risk factors for IFD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The diagnosis of cutaneous manifestations of deep mycoses relies on both histopathological and direct examinations. Yet, the current diagnostic criteria cannot prevent missed cases, including invasive aspergillosis, which requires the development of a novel diagnostic approach and imaging tools. We recently introduced the use of dynamic full-field optical coherence tomography (D-FF-OCT) in fungal diagnostics with a definition approaching that of conventional microscopy and the ability to return metabolic information regarding different fungal species. The present work focuses on subcellular dynamics and live-cell imaging of Aspergillus fumigatus with D-FF-OCT to follow the fungal growth stages., Methods: The A. fumigatus ATCC 204305 quality-control strain was used for all imaging experiments, following incubation times varying between 24 and 72 h at 30°C in a humidified chamber on Sabouraud dextrose agar. Fungal growth was subsequently monitored with D-FF-OCT for up to 5 h at room temperature and following the pharmacological stress of either voriconazole, amphotericin B, or caspofungin gradient concentration., Results: D-FF-OCT images allow not only the visualization of intracellular trafficking of vacuoles but also an evolving dynamic segmentation of conidiophores depending on the chronological development and aging of the hyphae or the effect of antifungal treatment. The same applies to conidial heads, with the most intense D-FF-OCT signal coming from vesicles, revealing a changing dynamic within a few hours only, as well as complete extinction following subsequent drying of the Sabouraud dextrose agar., Discussion: These results provide additional data on the ability of D-FF-OCT to monitor some of the main life cycle processes, dynamics, and intracellular trafficking of vacuoles in A. fumigatus , with or without the effect of pharmacological stress. Such complementary metabolic information could help both clinicians and microbiologists in either mechanistic studies toward experimental mycology or the development of a potential D-FF-OCT-guided diagnosis of superficial fungal infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Maldiney, Garcia-Hermoso, Sitterlé, Chassot, Thouvenin, Boccara, Blot, Piroth, Quenot, Charles, Aimanianda, Podac, Boulnois, Dalle, Sautour, Bougnoux and Lanternier.)

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.)

Dominant negative (DN) mutations in signal transducer and activator of transcription 3 (STAT3) are known to cause hyper-IgE syndrome, a rare primary immunodeficiency. STAT3 DN patients are prone to develop fungal infections, including chronic mucocutaneous candidiasis due to impaired IL-17-mediated immunity, and pulmonary aspergillosis. Despite having preserved phagocyte functions, STAT3 DN patients present connective tissue abnormalities and a defect in the immunological skin barrier. Fusarium species are ubiquitous molds, whose potential to infect humans depends on the host's innate and cellular immune status. Our aim was to describe four STAT3 DN patients with fusariosis confined to the skin. Medical records were reviewed and summarized. Four patients, aged 4, 11, 30, and 33 years, presented with chronic skin lesions which started in the extremities. Two patients had remote lesions, and none had systemic involvement. Skin biopsies showed mycelial threads with deep inflammatory-occasionally granulomatous-infiltrates, reaching the dermis; cultures grew Fusarium solani. Response to treatment was heterogeneous, often requiring multimodal therapies, including topical antifungal preparations. In this work, we describe primary invasive cutaneous fusariosis as a syndromic entity in four STAT3 DN patients., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Genomic analyses are widely applied to epidemiological, population genetic and experimental studies of pathogenic fungi. A wide range of methods are employed to carry out these analyses, typically without including controls that gauge the accuracy of variant prediction. The importance of tracking outbreaks at a global scale has raised the urgency of establishing high-accuracy pipelines that generate consistent results between research groups. To evaluate currently employed methods for whole-genome variant detection and elaborate best practices for fungal pathogens, we compared how 14 independent variant calling pipelines performed across 35 Candida auris isolates from 4 distinct clades and evaluated the performance of variant calling, single-nucleotide polymorphism (SNP) counts and phylogenetic inference results. Although these pipelines used different variant callers and filtering criteria, we found high overall agreement of SNPs from each pipeline. This concordance correlated with site quality, as SNPs discovered by a few pipelines tended to show lower mapping quality scores and depth of coverage than those recovered by all pipelines. We observed that the major differences between pipelines were due to variation in read trimming strategies, SNP calling methods and parameters, and downstream filtration criteria. We calculated specificity and sensitivity for each pipeline by aligning three isolates with chromosomal level assemblies and found that the GATK-based pipelines were well balanced between these metrics. Selection of trimming methods had a greater impact on SAMtools-based pipelines than those using GATK. Phylogenetic trees inferred by each pipeline showed high consistency at the clade level, but there was more variability between isolates from a single outbreak, with pipelines that used more stringent cutoffs having lower resolution. This project generated two truth datasets useful for routine benchmarking of C. auris variant calling, a consensus VCF of genotypes discovered by 10 or more pipelines across these 35 diverse isolates and variants for 2 samples identified from whole-genome alignments. This study provides a foundation for evaluating SNP calling pipelines and developing best practices for future fungal genomic studies.

Little is known about localized osteoarticular Scedosporiosis (LOS). Most data come from case reports and small case series. Here we present an ancillary study of the nationwide French Scedosporiosis Observational Study (SOS), describing 15 consecutive cases of LOS diagnosed between January 2005 and March 2017. Adult patients diagnosed with LOS defined by osteoarticular involvement without distant foci reported in SOS were included. Fifteen LOS were analyzed. Seven patients had underlying disease. Fourteen patients had prior trauma as potential inoculation. Clinical presentation was arthritis (n = 8), osteitis (n = 5), and thoracic wall infection (n = 2). The most common clinical manifestation was pain (n = 9), followed by localized swelling (n = 7), cutaneous fistulization (n = 7), and fever (n = 5). The species involved were Scedosporium apiospermum (n = 8), S. boydii (n = 3), S. dehoogii (n = 1), and Lomentospora prolificans (n = 3). The species distribution was unremarkable except for S. boydii, which was associated with healthcare-related inoculations. Management was based on medical and surgical treatment for 13 patients. Fourteen patients received antifungal treatment for a median duration of 7 months. No patients died during follow-up. LOS exclusively occurred in the context of inoculation or systemic predisposing factors. It has a non-specific clinical presentation and is associated with an overall good clinical outcome, provided there is a prolonged course of antifungal therapy and adequate surgical management., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Antibiotics disturb the intestinal bacterial microbiota, leading to gut dysbiosis and an increased risk for the overgrowth of opportunistic pathogens. It is not fully understood to what extent antibiotics affect the fungal fraction of the intestinal microbiota, the mycobiota. There is no report of the direct role of antibiotics in the overgrowth in healthy humans of the opportunistic pathogenic yeast Candida albicans. Here, we have explored the gut mycobiota of 22 healthy subjects before, during, and up to 6 months after a 3-day regimen of third-generation cephalosporins (3GCs). Using ITS1-targeted metagenomics, we highlighted the strong intra- and interindividual diversity of the healthy gut mycobiota. With a specific quantitative approach, we showed that C. albicans prevalence was much higher than previously reported, with all subjects but one being carriers of C. albicans, although with highly variable burdens. 3GCs significantly altered the mycobiota composition and the fungal load was increased both at short and long term. Both C. albicans relative and absolute abundances were increased but 3GCs did not reduce intersubject variability. Variations in C. albicans burden in response to 3GC treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity, with subjects characterized by a high increase of β-lactamase activity displaying a lower increase of C. albicans levels. A same antibiotic treatment might thus affect differentially the gut mycobiota and C. albicans carriage, depending on the treated subject, suggesting a need to adjust the current risk factors for C. albicans overgrowth after a β-lactam treatment. IMPORTANCE Fungal infections are redoubtable healthcare-associated complications in immunocompromised patients. Particularly, the commensal intestinal yeast Candida albicans causes invasive infections in intensive care patients and is, therefore, associated with high mortality. These infections are preceded by an intestinal expansion of C. albicans before its translocation into the bloodstream. Antibiotics are a well-known risk factor for C. albicans overgrowth but the impact of antibiotic-induced dysbiosis on the human gut mycobiota-the fungal microbiota-and the understanding of the mechanisms involved in C. albicans overgrowth in humans are very limited. Our study shows that antibiotics increase the fungal proportion in the gut and disturb the fungal composition, especially C. albicans, in a subject-dependent manner. Indeed, variations across subjects in C. albicans burden in response to β-lactam treatment could be partly explained by changes in the levels of endogenous fecal β-lactamase activity. This highlighted a potential new key factor for C. albicans overgrowth. Thus, the significance of our research is in providing a better understanding of the factors behind C. albicans intestinal overgrowth, which might lead to new means to prevent life-threatening secondary infections.

Background: Early diagnosis and prompt initiation of specific antifungal treatment are essential for improving the prognosis of mucormycosis. We aimed to assess the performance of serum Mucorales quantitative polymerase chain reaction (qPCR) for the early diagnosis and follow-up of mucormycosis., Methods: We prospectively enrolled 232 patients with suspicion of invasive mold disease, evaluated using standard imaging and mycological procedures. Thirteen additional patients with proven or probable mucormycosis were included to analyze DNA load kinetics. Serum samples were collected twice-a-week for Mucorales qPCR tests targeting the Mucorales genera Lichtheimia, Rhizomucor, and Mucor/Rhizopus., Results: The sensitivity was 85.2%, specificity 89.8%, and positive and negative likelihood ratios 8.3 and 0.17, respectively in this prospective study. The first Mucorales qPCR-positive serum was observed a median of 4 days (interquartile range [IQR], 0-9) before sampling of the first mycological or histological positive specimen and a median of one day (IQR, -2 to 6) before the first imaging was performed. Negativity of Mucorales qPCR within seven days after liposomal-amphotericin B initiation was associated with an 85% lower 30-day mortality rate (adjusted hazard ratio = 0·15, 95% confidence interval [.03-.73], P = .02)., Conclusions: Our study argues for the inclusion of qPCR for the detection of circulating Mucorales DNA for mucormycosis diagnosis and follow-up after treatment initiation. Positive results should be added to the criteria for the consensual definitions from the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium (EORTC/MSGERC), as already done for Aspergillus PCR., Competing Interests: Potential conflicts of interests. L. M. reports personal fees outside the submitted work and travel grants from Gilead and Pfizer. S. B. reports personal fees outside the submitted work and travel grants from Gilead. F. L. reports personal fees from Airnspace, Gilead, and F2G outside the submitted work. A. A. reports personal fees form Gilead and Pfizer outside the submitted work, consulting fees from Pfizer for serving on an Advisory Board; travel grants from Gilead and Pfizer; and patent licensed for Pneumocystis PCR and patent issued for Histoplasma PCR. F. D. reports travel grants from Pfizer to attend Trend in Medical Mycology congress, Aberdeen, 2021 and is Vice President for French Society of Medical Mycology. R. H. reports research grant from Gilead, personal fees form Gilead and Pfizer outside the submitted work, and travel grants from Gilead and Pfizer. A. P. B. reports support for attending meetings and/or travel from Gilead. BD reports fees for travel and as a speaker at 2 national congresses in 2021 from Gilead and consultancy fees at an expert meeting planned in 01/2022 from Pfizer. F. B. reports consulting fees, payment or honoraria, and support for attending meetings and/or travel from Gilead and support for attending meetings and/or travel from Pfizer and leadership or fiduciary role from the Society of French Medical Mycology. S. B. reports honorarium from Gilead to attend an educational workshop and support for attending meetings and/or travel from Gilead travel grant for TIMM congress Aberdeen UK. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Fusarium spp. are plant pathogens and opportunistic pathogens in severely immunocompromised (hematological malignancy, neutropenia, solid organ transplantation, etc.) and severely burned patients. Invasive fusariosis often disseminates and mortality remains high partly due to delayed diagnosis in the absence of a positive culture. The aim of our study is to design a quantitative PCR (qPCR) assay and evaluate the detection of Fusarium spp. DNA for early diagnosis of invasive infection. A qPCR assay was designed and optimized to identify all Fusarium species complex and secondarily evaluated on patient samples. A total of 81 blood samples from 15 patients diagnosed with proven invasive fusariosis from 9 centers in France were retrospectively tested. Circulating DNA was detected in 14 patients out of 15 (sensitivity of 93% [95% Confidence Interval (CI95), 70.1-99.7]). Detection was possible up to 18 days (median 6 days) before the diagnosis was confirmed by positive blood culture or biopsy. By comparison serum galactomannan and ß-D-glucan were positive in 7.1 and 58.3% of patients respectively. qPCR was negative for all patients with other invasive fungal diseases (IFD) tested (n = 12) and IFD-free control patients (n = 40). No cross-reactions were detected using DNA extracted from 81 other opportunistic fungi. We developed and validated a pan-Fusarium qPCR assay in serum/plasma with high sensitivity, specificity, and reproducibility that could facilitate early diagnosis and treatment monitoring of invasive fusariosis., Lay Abstract: Fusariosis ranks third among invasive mould infections. It is frequently diagnosed late due to the lack of specific tools. We designed and evaluated a new qPCR assay with high sensitivity and specificity allowing detection of Fusarium DNA in serum samples up to 18 days before conventional diagnosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Nannizziopsis spp., fungi responsible for emerging diseases, are rarely involved in human bone and joint infections. We present a rare case of septic arthritis with necrotizing cellulitis caused by N. obscura in a patient in France who had undergone kidney transplant. Rapid, aggressive medical and surgical management led to a favorable outcome.

Background: Cerebral aspergillosis (CA) is a life-threatening disease for which diagnosis and management remain challenging. Detailed analyses from large cohorts are lacking., Methods: We included 119 cases of proven (n = 54) or probable (n = 65) CA diagnosed between 2006 and 2018 at 20 French hospitals. Data were collected at baseline and during follow-up. Cerebral imaging was reviewed centrally by two neuroradiologists., Results: The most frequent underlying conditions were hematological malignancy (40%) and solid organ transplantation (29%). Galactomannan was detected in the serum of 64% of patients. In 75% of cases, at least one of galactomannan, Aspergillus PCR, and β-d-glucan was positive in the cerebrospinal fluid. Six-week mortality was 45%. Two distinct patterns of disease were identified according to presumed route of dissemination. Presumed haematogenous dissemination (n = 88) was associated with a higher frequency of impaired consciousness (64%), shorter time to diagnosis, the presence of multiple abscesses (70%), microangiopathy (52%), detection of serum galactomannan (69%) and Aspergillus PCR (68%), and higher six-week mortality (54%). By contrast, contiguous dissemination from the paranasal sinuses (n = 31) was associated with a higher frequency of cranial nerve palsy (65%), evidence of meningitis on cerebral imaging (83%), macrovascular lesions (61%), delayed diagnosis, and lower six-week mortality (30%). In multivariate analysis and in a risk prediction model, haematogenous dissemination, hematological malignancy and the detection of serum galactomannan were associated with higher six-week mortality., Conclusion: Distinguishing between hematogenous and contiguous dissemination patterns appears to be critical in the workup for CA, as they are associated with significant differences in clinical presentation and outcome., Competing Interests: Conflict of interest disclosure Dr Serris, Dr J. Benzakoun, Dr R. Porcher, Dr G. Hekimian, Dr L. Lelièvre, Dr F. Bonneville, Dr M-E. Bougnoux, Dr S. Houze, Dr S. Bretagne, Dr S Kremer, Dr V Letscher-Bru, Dr V. Pourcher, Dr S. Poirée, Dr FA, Dr P. Tattevin have nothing to declare., Dr. Danion reports personal fees from Gilead, outside the submitted work., Dr F. Cotton declares personal fees from Bayer Schering, Biogen IDEC, Bracco imaging, Guerbet, Novartis outside the submitted work., Dr M. Wolff declares lectures fees from MSD and from Correvio outside the submitted work., Dr A. Fekkar declares personal fees from Gilead, MSD, Pfizer and Janssen, outside the submitted work., Dr. Gangneux reports personal fees from Pfizer, personal fees from Gilead, outside the submitted work., Dr. Cassaing reports non-financial support and other from Gilead Sciences, non-financial support and other from Pfizer France, non-financial support and other from MSD france, outside the submitted work., Dr. Kremer reports personal fees from biogen, personal fees from alexion, personal fees from roche, personal fees from bayer, outside the submitted work., Pr. Lanternier reports personal fees from Gilead, F2G outside the submitted work., (Copyright © 2021 The British Infection Association. 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.)

We studied COVID-19 associated mucormycosis based on 17 cases reported nationwide and assessed the differences with India. They differed by frequencies of diabetes mellitus (47% in France versus up to 95% in India), hematological malignancies (35% versus 1%), anatomical sites (12% versus >80% rhino-orbito-cerebral) and prognosis (88% mortality versus <50%)., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Patients treated for adult T-Cell leukemia/lymphoma (ATL) have a poor prognosis and are prone to infectious complications which are poorly described. As the French reference center for ATL, we retrospectively analyzed 47 consecutive ATL (acute, n = 23; lymphoma, n = 14; chronic, n = 8; smoldering, n = 2) patients between 2006 and 2016 (median age 51 years, 96% Afro-Caribbean origin). The 3-year overall survival (OS) was 15.8%, 11.3%, and 85.7% for acute, lymphoma, and indolent (chronic and smoldering) forms respectively. Among aggressive subtypes, 20 patients received, as frontline therapy, high dose of zidovudine and interferon alfa (AZT-IFN⍺) resulting in an overall response rate (ORR) of 39% (complete response [CR] 33%) and 17 chemotherapy resulting of an ORR of 59% (CR 50%). Ninety-five infections occurred in 38 patients, most of whom had an acute subtype (n = 73/95; 77%). During their follow-up, patients receiving frontline chemotherapy or frontline AZT-IFNα developed infections in 74% (n = 14/19) and 89% (n = 24/27) of the cases respectively. Sixty-four (67%) of infections were microbiologically documented. Among them, invasive fungal infections (IFI, n = 11) included 2 Pneumocystis jirovecii pneumonia, 5 invasive aspergillosis, and 4 yeast fungemia. IFI exclusively occurred in patients with acute subtype mostly exposed to AZT-IFNα (n = 10/11) and experiencing prolonged (> 10 days) grade 4 neutropenia. Patients with aggressive subtype experiencing IFI had a lower OS than those who did not (median OS 5.4 months versus 18.4 months, p = 0.0048). ATL patients have a poor prognosis even in the modern era. Moreover, the high rate of infections impacts their management especially those exposed to AZT-IFNα., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Microsporidiosis is an emerging opportunistic infection in renal transplantation (RT) recipients. We aimed to describe its clinical presentation and treatment., Materials and Methods: We collected microsporidiosis cases identified in RT recipients between 2005 and 2019 in six French centers from the Crystal, Divat and Astre prospective databases., Results: We report 68 RT recipients with intestinal microsporidiosis; the patients were predominantly male (61.8%), with a median age of 58 (46-69) years. Infection occurred at a median time of 3 (0.8-6.8) years posttransplant. Only Enterocytozoon bieneusi was found. Microsporidiosis manifested as diarrhea (98.5% of patients) with weight loss (72.1%) and acute renal injury (57.4%) without inflammatory biological parameters. The therapeutic approaches were no treatment (N = 9), reduction of the immunosuppressive regimen (∆IS) (N = 22), fumagillin alone (N = 9), fumagillin and ∆IS (N = 19), and albendazole or nitazoxanide and ∆IS (N = 9). Overall clinical remission was observed in 60 patients (88.2%). We observed no acute kidney rejection, renal transplant failure, or death within 6 months after microsporidiosis., Conclusion: E. bieneusi is an underestimated opportunistic pathogen in RT recipients, and infection with E. bieneusi leads to diarrhea with important dehydration and acute renal injury. The treatment is based on the reduction of the immunosuppressive regimen and the administration of fumagillin if available., (© 2021 Wiley Periodicals LLC.)

It is now well known that patients with SARS-CoV-2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS-CoV-2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID-19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non-surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision., (© 2021 Wiley-VCH GmbH.)