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1. Invasive Aspergillosis with impaired neutrophil responses against Aspergillus fumigatus in patients treated with Acalabrutinib—findings from three cases

Author: Marion Blaize, Guillaume Thizy, Alexandre Boissonnas, Anaïs Portalier, Fanny Lanternier, Clémentine de La Porte des Vaux, Felipe Suarez, Marie-Elisabeth Bougnoux, Juliette Guitard, Arnaud Jabet, Nicolas Stocker, Abdelmalek Aoudjhane, Damien Roos-Weil, and Arnaud Fekkar
Subjects: Innate immune response, neutrophils, Bruton tyrosine kinase, BTK inhibitors, BTKi, ibrutinib, Infectious and parasitic diseases, RC109-216
Abstract: Objectives: Ibrutinib, a first-generation covalent Bruton's tyrosine kinase inhibitor (BTKi) was found to be a risk factor for the occurrence of invasive fungal complications. Acalabrutinib is a second-generation covalent BTKi used to treat B-cell malignancies. Healthy donor neutrophils incubated ex vivo with acalabrutinib lose ability to control Aspergillus conidia germination. In patients receiving acalabrutinib, the potential effect on neutrophil antifungal activity is unknown. Furthermore, only two cases of invasive aspergillosis have been reported during treatment with acalabrutinib, outside of a few cases in a clinical trial. Methods: We describe three new cases of invasive aspergillosis occurring within the first months of acalabrutinib therapy in patients with chronic lymphocytic leukemia. We used videomicroscopy and flow cytometry approaches to investigate the basic functional responses against Aspergillus of neutrophils from acalabrutinib-treated patients. Results: We showed an alteration in the anti-Aspergillus response after 1 month of acalabrutinb therapy: neutrophils lost their capacities of killing Aspergillus fumigatus germinating conidia and decreased their reactive oxygen species production when stimulated by Aspergillus. Conclusions: It is important to follow-up patients treated with acalabrutinib for the risk of aspergillosis as well as those treated with ibrutinib.
Published: 2024
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2. Sexually Transmitted Trichophyton mentagrophytes Genotype VII Infection among Men Who Have Sex with Men

Author: Arnaud Jabet, Sarah Dellière, Sophie Seang, Aziza Chermak, Luminita Schneider, Thibault Chiarabini, Alexandre Teboul, Geoffroy Hickman, Alizée Bozonnat, Cécile Brin, Marion Favier, Yanis Tamzali, François Chasset, Stéphane Barete, Samia Hamane, Mazzouz Benderdouche, Alicia Moreno-Sabater, Eric Dannaoui, Christophe Hennequin, Arnaud Fekkar, Renaud Piarroux, Anne-Cécile Normand, and Gentiane Monsel
Subjects: Tinea, sexually transmitted infections, Trichophyton mentagrophytes, monkeypox, HIV, terbinafine, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: Transmission of dermatophytes, especially Trichophyton mentagrophytes genotype VII, during sexual intercourse has been recently reported. We report 13 such cases in France. All patients were male; 12 were men who have sex with men. Our findings suggest sexual transmission of this pathogen within a specific population, men who have sex with men.
Published: 2023
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3. Enhancing antifungal treatment for chronic cavitary pulmonary aspergillosis through the addition of endobronchial valve therapy

Author: Thomas Maitre, Juliette Camuset, Morgane Faure, Christophe Cracco, Georgina Maalouf, Yves Allenbach, Matthias Barral, Arnaud Fekkar, Mihaela Giol, Antoine Parrot, and Jacques Cadranel
Subjects: Diseases of the respiratory system, RC705-779
Abstract: A 62-year-old male experienced anti-MDA5 dermatomyositis with lung involvement, treated with immunosuppressive therapy leading to chronic cavitary pulmonary aspergillosis in left upper lobe. Patient's history was complicated by complete left pneumothorax due to alveolar-pleural fistula occurring because of the rupture of the pulmonary cavitation. Left lung failed to re-expand despite a four-week period of pleural drainage. In addition to antifungal therapy, patient received endobronchial valve therapy in the anterior segmental bronchus of the left upper lobe leading to air leak cessation, left lung re expansion and aspergillosis cavitation closure.
Published: 2024
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4. Cerebral vasculitis due to Aspergillus spp. in immunocompromised patients: literature review

Author: Elie Haddad, Arnaud Fekkar, Sophie Bonnin, Natalia Shor, Danielle Seilhean, Isabelle Plu, Valérie Touitou, Véronique Leblond, Nicolas Weiss, Sophie Demeret, and Valérie Pourcher
Subjects: Aspergillosis, Fungal, Vasculitis, Cerebral infarction, Meningitis, Infectious and parasitic diseases, RC109-216
Abstract: 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.
Published: 2022
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5. Improving the Detection of Epidemic Clones in Candida parapsilosis Outbreaks by Combining MALDI-TOF Mass Spectrometry and Deep Learning Approaches

Author: Noshine Mohammad, Anne-Cécile Normand, Cécile Nabet, Alexandre Godmer, Jean-Yves Brossas, Marion Blaize, Christine Bonnal, Arnaud Fekkar, Sébastien Imbert, Xavier Tannier, and Renaud Piarroux
Subjects: MALDI TOF, epidemiology, Candida parapsilosis, neural network, artificial intelligence, outbreak, Biology (General), QH301-705.5
Abstract: Identifying fungal clones propagated during outbreaks in hospital settings is a problem that increasingly confronts biologists. Current tools based on DNA sequencing or microsatellite analysis require specific manipulations that are difficult to implement in the context of routine diagnosis. Using deep learning to classify the mass spectra obtained during the routine identification of fungi by MALDI-TOF mass spectrometry could be of interest to differentiate isolates belonging to epidemic clones from others. As part of the management of a nosocomial outbreak due to Candida parapsilosis in two Parisian hospitals, we studied the impact of the preparation of the spectra on the performance of a deep neural network. Our purpose was to differentiate 39 otherwise fluconazole-resistant isolates belonging to a clonal subset from 56 other isolates, most of which were fluconazole-susceptible, collected during the same period and not belonging to the clonal subset. Our study carried out on spectra obtained on four different machines from isolates cultured for 24 or 48 h on three different culture media showed that each of these parameters had a significant impact on the performance of the classifier. In particular, using different culture times between learning and testing steps could lead to a collapse in the accuracy of the predictions. On the other hand, including spectra obtained after 24 and 48 h of growth during the learning step restored the good results. Finally, we showed that the deleterious effect of the device variability used for learning and testing could be largely improved by including a spectra alignment step during preprocessing before submitting them to the neural network. Taken together, these experiments show the great potential of deep learning models to identify spectra of specific clones, providing that crucial parameters are controlled during both culture and preparation steps before submitting spectra to a classifier.
Published: 2023
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6. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004–2020

Author: Dea Garcia-Hermoso, Samia Hamane, Arnaud Fekkar, Arnaud Jabet, Blandine Denis, Martin Siguier, Guy Galeazzi, Elie Haddad, Sophie Brun, Valérie Vidal, Gilles Nevez, Rozenn Le Berre, Maud Gits-Muselli, Fanny Lanternier, and Stéphane Bretagne
Subjects: Nannizziopsis, Onygenales, invasive fungal infections, West Africa, emergence and immunosuppression, fungi, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification.
Published: 2020
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7. Occurrence of Candidemia in Patients with COVID-19 Admitted to Five ICUs in France

Author: Marion Blaize, Audrey Raoelina, Dimitri Kornblum, Laure Kamus, Alexandre Lampros, Marie Berger, Sophie Demeret, Jean-Michel Constantin, Antoine Monsel, Julien Mayaux, Charles-Edouard Luyt, Renaud Piarroux, and Arnaud Fekkar
Subjects: fungal infection, Candida, candidemia, candidiasis, fungemia, COVID-19, Biology (General), QH301-705.5
Abstract: Whether severe COVID-19 is by itself a significant risk factor for the development of candidemia currently remains an open question as conflicting results have been published. We aim to assess the occurrence of candidemia in patients with severe COVID-19 admitted to the intensive care unit (ICU). We conducted a retrospective study on patients with severe SARS-CoV-2-related pneumonia admitted to 5 ICUs in France who were specifically screened for fungal complications between March 2020 and January 2021. The study population included a total of 264 patients; the median age was 56 years old and most of them were male (n = 186; 70.5%) and immunocompetent (n = 225; 87.5%), and 62.7% (n = 153/244) were on extracorporeal membrane oxygenation support. Microbiological analysis included 4864 blood culture samples and beta-glucan test performed on 975 sera. Candidemia was diagnosed in 13 (4.9%) patients. The species involved were mainly C. albicans (n = 6) and C. parapsilosis (n = 5). Almost all patients (12/13; 92.3%) had a colonization by yeasts. ICU mortality was not significantly impacted by the occurrence of candidemia. Unrelated positive beta-glucan tests were observed in 49 patients (23.4%), including 6 with mold infections and 43 with false positive results. In our series, patients with severe SARS-CoV-2-related pneumonia seemed at low risk of developing invasive candidiasis.
Published: 2022
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8. Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France

Author: Laurène Tardieu, Gillian Divard, Olivier Lortholary, Anne Scemla, Éric Rondeau, Isabelle Accoceberry, Rémi Agbonon, Alexandre Alanio, Adela Angoulvant, Laetitia Albano, Philippe Attias, Anne Pauline Bellanger, Dominique Bertrand, Julie Bonhomme, Françoise Botterel, Nicolas Bouvier, Matthias Buchler, Taieb Chouaki, Thomas Crépin, Marie-Fleur Durieux, Guillaume Desoubeaux, Gary Doppelt, Loïc Favennec, Arnaud Fekkar, Ophélie Fourdinier, Marie Frimat, Jean-Pierre Gangneux, Claire Garandeau, Lilia Hasseine, Christophe Hennequin, Xavier Iriart, Nassim Kamar, Hannah Kaminski, Raphael Kormann, Laurence Lachaud, Christophe Legendre, Moglie Le Quintrec Donnette, Jordan Leroy, Charlène Levi, Marie Machouart, David Marx, Jean Menotti, Valérie Moal, Florent Morio, Natacha Mrozek, Muriel Nicolas, Philippe Poirier, Marie-Noelle Peraldi, Benjamin Poussot, Stéphane Ranque, Jean-Philippe Rerolle, Boualem Sendid, Renaud Snanoudj, Jérôme Tourret, Marc Vasse, Cécile Vigneau, Odile Villard, Laurent Mesnard, Fanny Lanternier, and Cédric Rafat
Subjects: cryptococcosis, opportunistic infection, transplant associated diseases, renal transplantation, cryptococcal meningitis, graft outcome, Medicine
Abstract: Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis.
Published: 2022
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9. Ibrutinib induces multiple functional defects in the neutrophil response against Aspergillus fumigatus

Author: Damien Blez, Marion Blaize, Carole Soussain, Alexandre Boissonnas, Aïda Meghraoui-Kheddar, Natacha Menezes, Anaïs Portalier, Christophe Combadière, Véronique Leblond, David Ghez, and Arnaud Fekkar
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Abstract: The Bruton tyrosine kinase inhibitor ibrutinib has become a leading therapy against chronic lymphoid leukemia. Recently, ibrutinib has been associated with the occurrence of invasive fungal infections, in particular invasive aspergillosis. The mechanisms underlying the increased susceptibility to fungal infections associated with exposure to ibrutinib are currently unknown. Innate immunity, in particular polymer-phonuclear neutrophils, represents the cornerstone of anti-Aspergillus immunity; however, the potential impact of ibrutinib on neutrophils has been little studied. Our study investigated the response to Aspergillus fumigatus and neutrophil function in patients with chronic lymphoid leukemia or lymphoma, who were undergoing ibrutinib therapy. We studied the consequences of ibrutinib exposure on the functions and anti-Aspergillus responses of neutrophils obtained from healthy donors and 63 blood samples collected at different time points from 32 patients receiving ibrutinib for lymphoid malignancies. We used both flow cytometry and video-microscopy approaches to analyze neutrophils’ cell surface molecule expression, cytokine production, oxidative burst, chemotaxis and killing activity against Aspergillus. Ibrutinib is associated, both in vitro and in patients under treatment, with multiple functional defects in neutrophils, including decreased production of reactive oxygen species, impairment of their capacity to engulf Aspergillus and inability to efficiently kill germinating conidia. Our results demonstrate that ibrutinib-exposed neutrophils develop significant functional defects that impair their response against Aspergillus fumigatus, providing a plausible explanation for the emergence of invasive aspergillosis in ibrutinib-treated patients.
Published: 2020
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10. Evaluation of the Chagas Western Blot IgG Assay for the Diagnosis of Chagas Disease

Author: Jean-Yves Brossas, Ballering Griselda, Margarita Bisio, Jeremy Guihenneuc, Julián Ernesto Nicolás Gulin, Stéphane Jauréguiberry, François-Xavier Lescure, Arnaud Fekkar, Dominique Mazier, Jaime Altcheh, and Luc Paris
Subjects: chagas disease, diagnostic, Trypanosoma cruzi, Medicine
Abstract: Chagas disease is a debilitating and often fatal pathology resulting from infection by the protozoan parasite Trypanosoma cruzi. In its recommendations, the World Health Organization states that the diagnosis of T. cruzi infection is usually based on the detection of antibodies against T. cruzi antigens and performed with two methodologically different assays. An inconclusive result can be resolved with a third “confirmatory” assay. The objective of this article is to evaluate the effectiveness of the Chagas Western Blot IgG assay (LDBio Diagnostics, Lyon, France) as a confirmatory serologic test. The Chagas Western Blot IgG assay was performed with native antigens derived from a T. cruzi strain of the TcVI genotype. Retrospective sera were provided by two parasitology laboratories (France and Argentina). The sensitivity, specificity, positive predictive value and negative predictive value of the Chagas blot were all 100% in our sera collection. The Chagas blot is an easy and qualitative method for the diagnosis of Chagas disease, with results in less than 2 h. This immunoblot has potential as a supplemental test for the confirmation of the presence of antibodies against T. cruzi in serum specimens. Nonetheless, the very good initial results presented here will need to be confirmed in larger studies.
Published: 2021
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11. Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient

Author: Marion Blaize, Julien Mayaux, Cécile Nabet, Alexandre Lampros, Anne-Geneviève Marcelin, Marc Thellier, Renaud Piarroux, Alexandre Demoule, and Arnaud Fekkar
Subjects: Aspergillus, SARS-CoV-2, aspergillosis, intensive care unit, mechanical ventilation, fungal superinfection, Medicine, Infectious and parasitic diseases, RC109-216
Abstract: Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease–associated pneumonia.
Published: 2020
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12. Clinical Origin and Species Distribution of Fusarium spp. Isolates Identified by Molecular Sequencing and Mass Spectrometry: A European Multicenter Hospital Prospective Study

Author: Anne-Cécile Normand, Sébastien Imbert, Sophie Brun, Abdullah M. S. Al-Hatmi, Erja Chryssanthou, Sophie Cassaing, Christine Schuttler, Lilia Hasseine, Caroline Mahinc, Damien Costa, Christine Bonnal, Stéphane Ranque, Marc Sautour, Elisa Rubio, Laurence Delhaes, Arnaud Riat, Boualem Sendid, Lise Kristensen, Marcel Brandenberger, Juliette Guitard, Ann Packeu, Renaud Piarroux, and Arnaud Fekkar
Subjects: fusariosis, mALDI ToF mass spectrometry, DNA sequencing, elongation factor, Fusarium species complex, Biology (General), QH301-705.5
Abstract: Fusarium spp. are widespread environmental fungi as well as pathogens that can affect plants, animals and humans. Yet the epidemiology of human fusariosis is still cloudy due to the rapidly evolving taxonomy. The Mass Spectrometry Identification database (MSI) has been developed since 2017 in order to allow a fast, accurate and free-access identification of fungi by matrix-assisted laser desorption ionization—time of flight (MALDI-TOF) mass spectrometry. Taking advantage of the MSI database user network, we aim to study the species distribution of Fusarium spp. isolates in an international multicenter prospective study. This study also allowed the assessment of the abilities of miscellaneous techniques to identify Fusarium isolates at the species level. The identification was performed by PCR-sequencing and phylogenic-tree approach. Both methods are used as gold standard for the evaluation of mass spectrometry. Identification at the species complex was satisfactory for all the tested methods. However, identification at the species level was more challenging and only 32% of the isolates were correctly identified with the National Center for Biotechnology Information (NCBI) DNA database, 20% with the Bruker MS database and 43% with the two MSI databases. Improvement of the mass spectrometry database is still needed to enable precise identification at the species level of any Fusarium isolates encountered either in human pathology or in the environment.
Published: 2021
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13. Aspergillus PCR in Bronchoalveolar Lavage Fluid for the Diagnosis and Prognosis of Aspergillosis in Patients With Hematological and Non-hematological Conditions

Author: Sébastien Imbert, Isabelle Meyer, Martine Palous, Jean-Yves Brossas, Madalina Uzunov, Feriel Touafek, Frédérick Gay, Valéry Trosini-Desert, and Arnaud Fekkar
Subjects: Aspergillus fumigatus, PCR, fungal infection, solid organ transplant, hematology, galactomannan, Microbiology, QR1-502
Abstract: Objectives: We evaluated the usefulness of an Aspergillus fumigatus quantitative PCR assay performed in bronchoalveolar lavage fluid (BAL) for the diagnosis and prognosis of both invasive and non-invasive aspergillosis.Methods: This 4-year retrospective study involved 613 at-risk patients who had either hematological disorders or other immunosuppressive conditions, notably solid organ transplants. Thirty-five patients had proven/probable aspergillosis and thirteen had chronic non-invasive aspergillosis. We compared PCR, galactomannan index and mycological analysis of BAL.Results: For invasive aspergillosis (IA), PCR performed in BAL yielded 88.6% sensitivity and 95.5% specificity. Comparatively, galactomannan index and mycological examination yielded only 56.3 and 63.6% sensitivity and 97.6 and 94.5% specificity, respectively. Considering the 13 chronic aspergillosis cases, PCR, galactomannan index and mycological examination yielded 76.9, 15.4, and 84.6% sensitivity and 92.2, 94.9, and 93% specificity, respectively. Fungal load in BAL evaluated by PCR was able to discriminate between aspergillosis and contamination, but not between invasive and non-invasive forms. Finally, fungal load was predictive of 90-day mortality, with 23.1% mortality for patients with less than 500 copies/mL versus 68.4% for patients above that cut-off (p < 0.05).Conclusion: Our results indicate that Aspergillus PCR in BAL is of particular interest for both the diagnosis and the prognosis of IA. It is likewise an interesting tool for the diagnosis of non-invasive forms.
Published: 2018
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14. Rapid species diagnosis for invasive candidiasis using mass spectrometry.

Author: Carine Marinach-Patrice, Arnaud Fekkar, Ralitsa Atanasova, Johanna Gomes, Laura Djamdjian, Jean-Yves Brossas, Isabelle Meyer, Pierre Buffet, Georges Snounou, Annick Datry, Christophe Hennequin, Jean-Louis Golmard, and Dominique Mazier
Subjects: Medicine, Science
Abstract: BACKGROUND: Matrix-assisted laser desorption ionisation time of flight mass spectrometry (MALDI TOF-MS) allows the identification of most bacteria and an increasing number of fungi. The potential for the highest clinical benefit of such methods would be in severe acute infections that require prompt treatment adapted to the infecting species. Our objective was to determine whether yeasts could be identified directly from a positive blood culture, avoiding the 1-3 days subculture step currently required before any therapeutic adjustments can be made. METHODOLOGY/PRINCIPAL FINDINGS: Using human blood spiked with Candida albicans to simulate blood cultures, we optimized protocols to obtain MALDI TOF-MS fingerprints where signals from blood proteins are reduced. Simulated cultures elaborated using a set of 12 strains belonging to 6 different species were then tested. Quantifiable spectral differences in the 5000-7400 Da mass range allowed to discriminate between these species and to build a reference database. The validation of the method and the statistical approach to spectral analysis were conducted using individual simulated blood cultures of 36 additional strains (six for each species). Correct identification of the species of these strains was obtained. CONCLUSIONS/SIGNIFICANCE: Direct MALDI TOF-MS analysis of aliquots from positive blood cultures allowed rapid and accurate identification of the main Candida species, thus obviating the need for sub-culturing on specific media. Subsequent to this proof-of-principle demonstration, the method can be extended to other clinically relevant yeast species, and applied to an adequate number of clinical samples in order to establish its potential to improve antimicrobial management of patients with fungemia.
Published: 2010
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15. Hospital Clonal Outbreak of Fluconazole-Resistant Candida parapsilosis Harboring the Y132F ERG11p Substitution in a French Intensive Care Unit

Author: Simona Presente, Christine Bonnal, Anne-Cécile Normand, Yannick Gaudonnet, Arnaud Fekkar, Jean-François Timsit, and Solen Kernéis
Subjects: Pharmacology, Infectious Diseases, Pharmacology (medical)
Abstract: We report the first identification of a fluconazole-resistant Candida parapsilosis (FR- Cp ) strain in our hospital, which subsequently caused an outbreak involving 17 patients (12 deaths) within a 26-bed French intensive care unit. Microsatellite genotyping confirmed that all FR- Cp isolates belonged to the same clone.
Published: 2023

16. Gradient concentration strip–specific epidemiological cut-off values of antifungal drugs in various yeast species and five prevalent Aspergillus species complexes

Author: Victor Mercier, Valérie Letscher-Bru, Marie-Elisabeth Bougnoux, Laurence Delhaes, Francoise Botterel, Danièle Maubon, Frédéric Dalle, Alexandre Alanio, Sandrine Houzé, Eric Dannaoui, Carole Cassagne, Sophie Cassaing, Marie-Fleur Durieux, Arnaud Fekkar, Jean-Philippe Bouchara, Jean-Pierre Gangneux, Julie Bonhomme, Damien Dupont, Damien Costa, Boualem Sendid, Taieb Chouaki, Nathalie Bourgeois, Antoine Huguenin, Sophie Brun, Caroline Mahinc, Lilia Hasseine, Solène Le Gal, Anne-Pauline Bellanger, Eric Bailly, Florent Morio, Céline Nourrisson, Nicole Desbois-Nogard, Estelle Perraud-Cateau, Anne Debourgogne, Hélène Yéra, Laurence Lachaud, Milène Sasso, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Dynamique des interactions hôte pathogène (DIHP), Université de Strasbourg (UNISTRA), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU de Bordeaux Pellegrin [Bordeaux], Centre de recherche Cardio-Thoracique de Bordeaux [Bordeaux] (CRCTB), Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Institut Agro Dijon, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Hopital Saint-Louis [AP-HP] (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Cité (UPCité), Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Limoges, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Infections Respiratoires Fongiques (IRF), Université d'Angers (UA)-Université de Brest (UBO), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Laboratoire de Parasitologie-Mycologie [CHU Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hospices Civils de Lyon (HCL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Département de microbiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Hôpital Avicenne [AP-HP], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre hospitalier universitaire de Nantes (CHU Nantes), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Nantes Université - UFR des Sciences Pharmaceutiques et Biologiques (Nantes Univ - UFR Pharmacie), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU de la Martinique [Fort de France], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Ecologie et biologie des interactions (EBI), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Stress, Immunité, Pathogènes (SIMPA), Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de parasitologie-mycologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)
Subjects: Microbiology (medical), Gradient concentration strip–specific, Infectious Diseases, Aspergillus, Epidemiological cut-off values, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV]Life Sciences [q-bio], [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Antifungal susceptibility, Candida
Abstract: International audience; 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.
Published: 2022

17. Myélite postérieure étendue isolée à Aspergillus fumigatus chez un patient sans immunodépression connue

Author: Lina Jeantin, Delphine Leclercq, Suzanne Tran, Arnaud Fekkar, Fanny Lanternier, Marois Clémence, and Adam Celier
Subjects: Neurology, Neurology (clinical)
Published: 2023

18. Identification des moisissures au laboratoire de routine hospitalière

Author: Renaud Piarroux, Anne-Cécile Normand, Marion Blaize, and Arnaud Fekkar
Subjects: 03 medical and health sciences, Medical Laboratory Technology, 0302 clinical medicine, 030220 oncology & carcinogenesis, Biochemistry (medical), 030204 cardiovascular system & hematology, Analytical Chemistry
Abstract: Resume La presence de moisissures en culture au laboratoire n’est pas rare et leur identification participe au diagnostic et a la prise en charge des patients. Les techniques d’identification des champignons filamenteux ont considerablement evolue depuis les annees 2000 : a l’identification morphologique necessitant une expertise importante se sont ajoutees des approches de biologie moleculaire basees sur la comparaison de sequences d’ADN ou de type Maldi-TOF (Matrix Assisted Laser Desorption Ionization - Time of Flight) comparant des profils proteiques a des bases de donnees de plus en plus fournies. Ces nouvelles techniques bien que plus couteuses que l’identification morphologique, permettent des identifications robustes et meme de decrire de nouvelles especes ou complexes d’especes. Toutefois des erreurs ne sont pas a exclure et le role des techniciens et biologistes au sein des laboratoires reste essentiel pour analyser, critiquer et interpreter les resultats obtenus par ces nouvelles technologies et les confronter au contexte clinique des patients.
Published: 2021

19. Occurrence of Invasive Pulmonary Fungal Infections in Patients with Severe COVID-19 Admitted to the ICU

Author: Sophie Demeret, Alexandre Lampros, Antoine Monsel, Corentin Poignon, Arnaud Fekkar, Anne-Geneviève Marcelin, Jean-Michel Constantin, Julien Mayaux, Marion Blaize, Charles-Edouard Luyt, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Service de Neurophysiologie [CHU Pitié-Salpêtrière], Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Pulmonary Fungal Infections, Coronavirus disease 2019 (COVID-19), viruses, Disease, Critical Care and Intensive Care Medicine, medicine.disease_cause, Aspergillosis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, aspergillosis, In patient, 030212 general & internal medicine, Significant risk, Coronavirus, SARS-CoV-2, business.industry, fungal infection, aspergillus, COVID-19, virus diseases, Retrospective cohort study, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, business
Abstract: International audience; Rationale:Whether severe coronavirus disease (COVID-19) is a significant risk factor for the development of invasive fungal superinfections is of great medical interest and remains, for now, an open question.Objectives: We aim to assess the occurrence of invasive fungal respiratory superinfections in patients with severe COVID-19.Methods: We conducted the study on patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–related pneumonia admitted to five ICUs in France who had respiratory and serum sampling performed for specific screening of fungal complications.Measurements and Main Results: The study population included a total of 145 patients; the median age was 55 years old. Most of them were male (n = 104; 72%), were overweight (n = 99; 68%), and had hypertension (n = 83; 57%) and diabetes (n = 46; 32%). Few patients presented preexisting host risk factors for invasive fungal infection (n = 20; 14%). Their global severity was high; all patients were on invasive mechanical ventilation, and half (n = 73, 54%) were on extracorporeal membrane oxygenation support. Mycological analysis included 2,815 mycological tests (culture, galactomannan, β-glucan, and PCR) performed on 475 respiratory samples and 532 sera. A probable/putative invasive pulmonary mold infection was diagnosed in 7 (4.8%) patients and linked to high mortality. Multivariate analysis indicates a significantly higher risk for solid organ transplant recipients (odds ratio, = 4.66; interquartile range, 1.98–7.34; P = 0.004). False-positive fungal test and clinically irrelevant colonization, which did not require the initiation of antifungal treatment, was observed in 25 patients (17.2%).Conclusions: In patients with no underlying immunosuppression, severe SARS-CoV-2–related pneumonia seems at low risk of invasive fungal secondary infection, especially aspergillosis.
Published: 2021

20. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study

Author: Gilles Nevez, Brice Autier, Jean-Pierre Gangneux, Yves Cohen, Nadine François, Cécile Aubron, Emmanuel Canet, Sophie Brun, Alexandre Alanio, Philippe Seguin, Nicolas Terzi, Bruno Mégarbane, Jean-François Timsit, Romain Pelletier, Marie Soulié, Dorothée Quinio, Estelle Sabourin, Nicolas de Prost, Juliette Guitard, Frederique Boquel, Valérie Letscher-Bru, Jeff Morcet, Stephan Ehrmann, Guillaume Voiriot, Solène Le Gal, Florent Morio, Bruno Laviolle, Jean-Christophe Richard, Laurent Argaud, Estelle Cateau, Marion Blaize, Matthieu Lesouhaitier, Patrice Le Pape, Carole Schwebel, Florent Wallet, Jordan Leroy, Jean-Ralph Zahar, Ana Novara, Hélène Guegan, Béatrice Riu-Poulenc, Florence Robert-Gangneux, Jean Menotti, Eric Dannaoui, Sorya Belaz, Yves Le Tulzo, Muriel Cornet, Saad Nseir, Ferhat Meziani, Damien Dupont, Boualem Sendid, Antoine Monsel, Florian Reizine, Xavier Iriart, Francoise Botterel, Arnaud Fekkar, Charles-Edouard Luyt, Cécile Garnaud, Melek Manai, Lionel Lamhaut, Jean-Marc Tadié, Julien Mayaux, Sylvie Paulus, Florence Persat, Marie-Elisabeth Bougnoux, Christophe Hennequin, Christine Bonnal, Arnaud W. Thille, Antoine Berry, Sandrine Houze, Guillaume Desoubeaux, Centre Hospitalier Universitaire [Rennes], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Avicenne [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Necker - Enfants Malades [AP-HP], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, and CarMeN, laboratoire
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Intensive care, Internal medicine, medicine, Humans, education, Mechanical ventilation, education.field_of_study, Coinfection, SARS-CoV-2, business.industry, Mucormycosis, COVID-19, Articles, Odds ratio, medicine.disease, [SDV] Life Sciences [q-bio], Mycoses, business, Cohort study
Abstract: International audience; 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 (\textgreater14 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 (\textless1%) 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\textless0·0001). 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.
Published: 2022

21. Antifungal susceptibility of 182 fusarium species isolates from 20 european centers:Comparison between eucast and gradient concentration strip methods

Author: Marcel Brandenberger, Elisa Rubio, Lise Kristensen, Renaud Piarroux, Anne-Cécile Normand, Boualem Sendid, Erja Chryssanthou, Christine Bonnal, Abdullah M. S. Al-Hatmi, Dirk Stubbe, Arnaud Fekkar, Damien Costa, Arnaud Riat, Sophie Cassaing, Christine Schuttler, Marc Sautour, Sophie Brun, Marion Blaize, Lilia Hasseine, Sébastien Imbert, Laurence Delhaes, Stéphane Ranque, Caroline Mahinc, Sorbonne Université (SU), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), and Sorbonne Université - Faculté de Médecine (SU FM)
Subjects: Fusarium, Antifungal, Veterinary medicine, Posaconazole, Antifungal Agents, medicine.drug_class, Antifungal drugs, Comparison, Microbial Sensitivity Tests, terbinafine, Amphotericin B/pharmacology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, medicine, voriconazole, antifungal susceptibility, Pharmacology (medical), [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, EUCAST, Gradient concentration strips, Etest, Pharmacology, Voriconazole, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, Voriconazole/pharmacology, Isavuconazole, ECV, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, posaconazole, amphotericin B, Infectious Diseases, Susceptibility, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Antifungal Agents/pharmacology, Terbinafine, medicine.drug
Abstract: We determined the susceptibility of 182 Fusarium species isolates to five antifungal drugs (amphotericin B, voriconazole, posaconazole, isavuconazole, and terbinafine) by the EUCAST method. Based on the latest taxonomic insights, isolates collected from 20 European centers were distributed into seven complexes and 27 species. The susceptibility was variable, depending on the species. Comparison with the gradient concentration strip method, which was used for 77 isolates, showed essential agreement values for voriconazole, posaconazole, isavuconazole, and amphotericin B of 17%, 91%, 83%, and 70%, respectively.
Published: 2021

22. COVID-19–related Respiratory Failure and Lymphopenia Do Not Seem Associated with Pneumocystosis

Author: Marion Blaize, Charles Edouard Luyt, Arnaud Fekkar, Julien Mayaux, Alexandre Lampros, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie et Réanimation Médicale [CHU Pitié-Salpêtrière] (Département ' R3S '), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases [IHU ICAN], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP]
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), [SDV]Life Sciences [q-bio], Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pneumocystis carinii, Critical Care and Intensive Care Medicine, Broncho-alveolar lavage, 03 medical and health sciences, 0302 clinical medicine, Lymphopenia, Correspondence, Pneumocystosis, medicine, Humans, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Coinfection, SARS-CoV-2, 030306 microbiology, business.industry, Pneumonia, Pneumocystis, COVID-19, medicine.disease, 3. Good health, Respiratory failure, Immunology, Respiratory Insufficiency, business
Abstract: International audience
Published: 2020

23. Etest ECVs/ECOFFs for detection of resistance in prevalent and three non-prevalent Candida spp. to triazoles and amphotericin B and Aspergillus spp. to caspofungin: Further assessment of modal variability

Author: Damien Dupont, John D. Turnidge, J Fuller, Maiken Cavling Arendrup, A Forastiero, M Dehais, Emilia Cantón, Hélène Guegan, Nathalie Bourgeois, Ana Espinel-Ingroff, Guillermo Garcia-Effron, Laurence Delhaes, B. Bouteille, Teresa Peláez, J Garcia, Cornelia Lass-Flörl, Jesús Guinea, Arnaud Fekkar, Nelesh P. Govender, Françoise Botterel, Eric Dannaoui, Gloria M. González, R Magobo, Sophie Cassaing, Michaela Lackner, Milène Sasso, Sandrine Houzé, Virginia Commonwealth University (VCU), Hôpital Lapeyronie [Montpellier] (CHU), University of Adelaide, Statens Serum Institut [Copenhagen], CHU Henri Mondor, CHU Limoges, CHU Toulouse [Toulouse], Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), CHU Bordeaux [Bordeaux], Hospices Civils de Lyon, Departement de Neurologie (HCL), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Western Ontario (UWO), Universidad Nacional del Litoral [Santa Fe] (UNL), Hospital Universitario La Paz, Universidad Autonoma de Nuevo Leon [Mexique] (UANL), National Institute for Communicable Diseases [Johannesburg] (NICD), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hospital General Universitario 'Gregorio Marañón' [Madrid], Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Leopold Franzens Universität Innsbruck - University of Innsbruck, Universidad de Oviedo [Oviedo], CHU Henri Mondor [Créteil], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), and Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité)
Subjects: Posaconazole, [SDV]Life Sciences [q-bio], Aspergillus fumigatus, Microbiology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Amphotericin B, medicine, Pharmacology (medical), 030212 general & internal medicine, caspofungin, Candida albicans, triazoles, Etest, Candida, Aspergillus spp., Candida, ECOFFS, ECVs, ERG11 mutants, amphotericin B, antifungal resistance, caspofungin, nonprevalent Candida, triazoles, Pharmacology, Voriconazole, ECOFFS, 0303 health sciences, biology, 030306 microbiology, ERG11 mutants, antifungal resistance, biochemical phenomena, metabolism, and nutrition, biology.organism_classification, bacterial infections and mycoses, amphotericin B, Aspergillus spp, nonprevalent Candida, Infectious Diseases, chemistry, ECVs, Caspofungin, Fluconazole, medicine.drug
Abstract: International audience; Susceptibility testing is an important tool in the clinical setting; its utility is based on the availability of categorical endpoints, breakpoints (BPs) or epidemiological cutoff values (ECVs/ECOFFs). CLSI and EUCAST have developed antifungal susceptibility testing, BPs and ECVs for some fungal species. Although the Concentration Gradient Strip BioMerieux Etest is useful for routine testing in the clinical laboratory, ECVs are not available for all agent/species; the lack of clinical data precludes development of BPs. We re-evaluated and consolidated Etest data points from three previous studies, and included new data. We defined ECOFFinder Etest ECVs for three sets of species/agent combinations: fluconazole, posaconazole and voriconazole and 8 Candida spp.; amphotericin B and 3 non-prevalent Candida spp.; and caspofungin and 5 Aspergillus spp. The total of Etest MICs from 23 laboratories (Europe, the Americas, South Africa) included (antifungal agent/dependent): 17,242 Candida albicans, 244 C. dubliniensis, 5,129 C. glabrata species complex (SC), 275 C. guilliermondii (Meyerozyma guilliermondii), 1,133 C. krusei (Pichia kudriavzevii), 933 C. kefyr (Kluyveromyces marxianus), 519 C. lusitaniae (Clavispora lusitaniae), 2,947 C. parapsilosis SC, 2,214 C. tropicalis, 3,212 Aspergillus fumigatus, 232 A. flavus, 181 A. niger, and 267 A. terreus SC isolates. Triazole MICs for 66 confirmed non-wild-type (non-WT) Candida isolates were available (ERG11 point mutations). Distributions fulfilling CLSI ECV criteria were pooled and ECOFFinder Etest ECVs were established for triazoles (9 Candida spp.); amphotericin B (3 less-prevalent Candida spp.) and caspofungin (4 Aspergillus spp.). Etest fluconazole ECVs could be good detectors of Candida non-WT isolates (59/61 Non-WT: 4 of 6 species).
Published: 2021

24. Autoantibodies neutralizing type I IFNs are present in

Author: Paul, Bastard, Adrian, Gervais, Tom, Le Voyer, Jérémie, Rosain, Quentin, Philippot, Jérémy, Manry, Eleftherios, Michailidis, Hans-Heinrich, Hoffmann, Shohei, Eto, Marina, Garcia-Prat, Lucy, Bizien, Alba, Parra-Martínez, Rui, Yang, Liis, Haljasmägi, Mélanie, Migaud, Karita, Särekannu, Julia, Maslovskaja, Nicolas, de Prost, Yacine, Tandjaoui-Lambiotte, Charles-Edouard, Luyt, Blanca, Amador-Borrero, Alexandre, Gaudet, Julien, Poissy, Pascal, Morel, Pascale, Richard, Fabrice, Cognasse, Jesus, Troya, Sophie, Trouillet-Assant, Alexandre, Belot, Kahina, Saker, Pierre, Garçon, Jacques G, Rivière, Jean-Christophe, Lagier, Stéphanie, Gentile, Lindsey B, Rosen, Elana, Shaw, Tomohiro, Morio, Junko, Tanaka, David, Dalmau, Pierre-Louis, Tharaux, Damien, Sene, Alain, Stepanian, Bruno, Megarbane, Vasiliki, Triantafyllia, Arnaud, Fekkar, James R, Heath, José Luis, Franco, Juan-Manuel, Anaya, Jordi, Solé-Violán, Luisa, Imberti, Andrea, Biondi, Paolo, Bonfanti, Riccardo, Castagnoli, Ottavia M, Delmonte, Yu, Zhang, Andrew L, Snow, Steven M, Holland, Catherine, Biggs, Marcela, Moncada-Vélez, Andrés Augusto, Arias, Lazaro, Lorenzo, Soraya, Boucherit, Boubacar, Coulibaly, Dany, Anglicheau, Anna M, Planas, Filomeen, Haerynck, Sotirija, Duvlis, Robert L, Nussbaum, Tayfun, Ozcelik, Sevgi, Keles, Ahmed A, Bousfiha, Jalila, El Bakkouri, Carolina, Ramirez-Santana, Stéphane, Paul, Qiang, Pan-Hammarström, Lennart, Hammarström, Annabelle, Dupont, Alina, Kurolap, Christine N, Metz, Alessandro, Aiuti, Giorgio, Casari, Vito, Lampasona, Fabio, Ciceri, Lucila A, Barreiros, Elena, Dominguez-Garrido, Mateus, Vidigal, Mayana, Zatz, Diederik, van de Beek, Sabina, Sahanic, Ivan, Tancevski, Yurii, Stepanovskyy, Oksana, Boyarchuk, Yoko, Nukui, Miyuki, Tsumura, Loreto, Vidaur, Stuart G, Tangye, Sonia, Burrel, Darragh, Duffy, Lluis, Quintana-Murci, Adam, Klocperk, Nelli Y, Kann, Anna, Shcherbina, Yu-Lung, Lau, Daniel, Leung, Matthieu, Coulongeat, Julien, Marlet, Rutger, Koning, Luis Felipe, Reyes, Angélique, Chauvineau-Grenier, Fabienne, Venet, Guillaume, Monneret, Michel C, Nussenzweig, Romain, Arrestier, Idris, Boudhabhay, Hagit, Baris-Feldman, David, Hagin, Joost, Wauters, Isabelle, Meyts, Adam H, Dyer, Sean P, Kennelly, Nollaig M, Bourke, Rabih, Halwani, Narjes Saheb, Sharif-Askari, Karim, Dorgham, Jérome, Sallette, Souad Mehlal, Sedkaoui, Suzan, AlKhater, Raúl, Rigo-Bonnin, Francisco, Morandeira, Lucie, Roussel, Donald C, Vinh, Sisse Rye, Ostrowski, Antonio, Condino-Neto, Carolina, Prando, Anastasiia, Bonradenko, András N, Spaan, Laurent, Gilardin, Jacques, Fellay, Stanislas, Lyonnet, Kaya, Bilguvar, Richard P, Lifton, Shrikant, Mane, Mark S, Anderson, Bertrand, Boisson, Vivien, Béziat, Shen-Ying, Zhang, Evangelos, Vandreakos, Olivier, Hermine, Aurora, Pujol, Pärt, Peterson, Trine H, Mogensen, Lee, Rowen, James, Mond, Stéphanie, Debette, Xavier, de Lamballerie, Xavier, Duval, France, Mentré, Marie, Zins, Pere, Soler-Palacin, Roger, Colobran, Guy, Gorochov, Xavier, Solanich, Sophie, Susen, Javier, Martinez-Picado, Didier, Raoult, Marc, Vasse, Peter K, Gregersen, Lorenzo, Piemonti, Carlos, Rodríguez-Gallego, Luigi D, Notarangelo, Helen C, Su, Kai, Kisand, Satoshi, Okada, Anne, Puel, Emmanuelle, Jouanguy, Charles M, Rice, Pierre, Tiberghien, Qian, Zhang, Aurélie, Cobat, Laurent, Abel, and Hind, Hamzeh-Cognasse
Subjects: Adult, Aged, 80 and over, Adolescent, Critical Illness, Infant, Newborn, COVID-19, Infant, Interferon-alpha, Middle Aged, Antibodies, Neutralizing, Young Adult, Case-Control Studies, Child, Preschool, Immunoglobulin G, Interferon Type I, Humans, Child, Aged, Autoantibodies
Abstract: Circulating autoantibodies (auto-Abs) neutralizing high concentrations (10 ng/mL, in plasma diluted 1 to 10) of IFN-α and/or -ω are found in about 10% of patients with critical COVID-19 pneumonia, but not in subjects with asymptomatic infections. We detect auto-Abs neutralizing 100-fold lower, more physiological, concentrations of IFN-α and/or -ω (100 pg/mL, in 1/10 dilutions of plasma) in 13.6% of 3,595 patients with critical COVID-19, including 21% of 374 patients80 years, and 6.5% of 522 patients with severe COVID-19. These antibodies are also detected in 18% of the 1,124 deceased patients (aged 20 days-99 years; mean: 70 years). Moreover, another 1.3% of patients with critical COVID-19 and 0.9% of the deceased patients have auto-Abs neutralizing high concentrations of IFN-β. We also show, in a sample of 34,159 uninfected subjects from the general population, that auto-Abs neutralizing high concentrations of IFN-α and/or -ω are present in 0.18% of individuals between 18 and 69 years, 1.1% between 70 and 79 years, and 3.4%80 years. Moreover, the proportion of subjects carrying auto-Abs neutralizing lower concentrations is greater in a subsample of 10,778 uninfected individuals: 1% of individuals70 years, 2.3% between 70 and 80 years, and 6.3%80 years. By contrast, auto-Abs neutralizing IFN-β do not become more frequent with age. Auto-Abs neutralizing type I IFNs predate SARS-CoV-2 infection and sharply increase in prevalence after the age of 70 years. They account for about 20% of both critical COVID-19 cases in the over-80s, and total fatal COVID-19 cases.
Published: 2021

25. Invasive aspergillosis due to Aspergillus cryptic species: A prospective multicentre study

Author: Laurence Lachaud, Christine Schuttler, Damien Costa, Lilia Hasseine, Sophie Cassaing, Marion Blaize, Juliette Guitard, Frédéric Gabriel, Sébastien Imbert, Sophie Brun, Renaud Piarroux, Arnaud Fekkar, Anne-Cécile Normand, Marijke Hendrickx, Hélène Raberin, Christine Bonnal, Lise Kristensen, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Bordeaux [Bordeaux], CHU Rouen, Normandie Université (NU), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Nice (CHU Nice), Aarhus University Hospital, Service de Parasitologie - Mycologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), CHU Saint-Etienne, Hôpital Avicenne [AP-HP], Institut Scientifique de Santé Publique [Belgique] - Scientific Institute of Public Health [Belgium] (WIV-ISP), Réseau International des Instituts Pasteur (RIIP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), CHU Saint-Antoine [AP-HP], and Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E)
Subjects: Adult, Male, Species complex, Antifungal Agents, Aspergillus calidoustus, Dermatology, Aspergillosis, molecular epidemiology, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Species level, Drug Resistance, Fungal, medicine, Humans, EUCAST, 030212 general & internal medicine, Prospective Studies, Sensu stricto, Aged, azole prophylaxis, High rate, Invasive Pulmonary Aspergillosis, cryptic species, invasive aspergillosis, 0303 health sciences, Aspergillus, Molecular epidemiology, biology, 030306 microbiology, General Medicine, antifungal resistance, Middle Aged, biology.organism_classification, medicine.disease, Infectious Diseases, Aspergillus sublatus, Invasive aspergillosis, Female, France, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; ObjectivesAspergillus cryptic species are increasingly recognised causes of Aspergillus diseases, including life-threatening invasive aspergillosis (IA). However, as their accurate identification remains challenging in a routine practice, few is known from a clinical and epidemiological perspective. Recently, the MSI application has emerged as a powerful tool for the detection and identification of Aspergillus cryptic species. We aimed to use to the network of users of the MSI application to conduct a multicentre prospective screening of Aspergillus cryptic species-related IA and analyse their epidemiological, clinical and mycological characteristics.MethodsOver a 27-month period, the clinical involvement of 369 Aspergillus cryptic isolates, from 13 French and Danish MSI application users, was prospectively analysed. Species identification was confirmed by DNA-sequencing and antifungal susceptibility testing was performed using EUCAST reference method. Fifty-one A fumigatus sensu stricto invasive cases were also analysed.ResultsFifteen cryptic isolates were responsible of IA. Eight species were involved, including 5 cases related to the species A sublatus. These species showed high rate of in vitro low susceptibility to antifungal drugs. In comparison with A fumigatus sensu stricto invasive cases, pre-exposure to azole drugs was significantly associated with cryptic IA (P = .02).DiscussionThis study brings new insights in cryptic species related IA and underlines the importance to identify accurately at the species level these Aspergillus isolates. The increasing use of antifungal drugs might lead in the future to an epidemiologic shift with an emergence of resistant isolates involved in IA.
Published: 2021

26. Earliest case of Candida auris infection imported in 2007 in Europe from India prior to the 2009 description in Japan

Author: Marie Desnos-Ollivier, Stéphane Bretagne, Arnaud Fekkar, Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris], Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by Institut Pasteur and Santé Publique France., We thank the Mutualized Platform for Microbiology (P2M, Institut Pasteur, Paris, France) for whole genome sequencing., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Centre d'Immunologie et des Maladies Infectieuses (CIMI), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AUGUSTE, Christèle, Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: Whole genome sequencing, 0303 health sciences, whole genome sequencing, 030306 microbiology, short tandem repeat, Outbreak, India, Biology, Candida auris, Virology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 3. Good health, Multiple drug resistance, Europe, 03 medical and health sciences, Emerging pathogen, Infectious Diseases, Clade, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience; Candida auris is an emerging pathogen frequently associated with multidrug resistance and involved in many worldwide outbreaks. We here report the first European imported case in France due to isolate belonging of the South Indian clade I and the importance of prevention measure to avoid fungal spreading.
Published: 2021

27. Clinical Origin and Species Distribution of Fusarium spp. Isolates Identified by Molecular Sequencing and Mass Spectrometry: A European Multicenter Hospital Prospective Study

Author: Damien Costa, Abdullah M. S. Al-Hatmi, Marcel Brandenberger, Renaud Piarroux, Christine Schuttler, Anne-Cécile Normand, Elisa Rubio, Lilia Hasseine, Sophie Cassaing, Laurence Delhaes, Lise Kristensen, Caroline Mahinc, Arnaud Fekkar, Sébastien Imbert, Stéphane Ranque, Sophie Brun, Ann Packeu, Juliette Guitard, Boualem Sendid, C. Bonnal, Arnaud Riat, Marc Sautour, Erja Chryssanthou, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Radboud University Medical Center [Nijmegen], Karolinska Institutet [Stockholm], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Rouen, Normandie Université (NU), CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Barcelona, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), CHU de Bordeaux Pellegrin [Bordeaux], Geneva University Hospitals and Geneva University, CHU Lille, Aarhus University Hospital, Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Service de Parasitologie - Mycologie [CHU Saint-Antoine], Gestionnaire, Hal Sorbonne Université, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Radboud University Medical Centre [Nijmegen, The Netherlands], CHU Toulouse [Toulouse], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Centre d'Immunologie et de Maladies Infectieuses (CIMI)
Subjects: Microbiology (medical), Fusariosis, Fusarium, Species complex, MALDI ToF mass spectrometry, [SDV]Life Sciences [q-bio], Species distribution, fusariosis, mALDI ToF mass spectrometry, Plant Science, Computational biology, Biology, Mass spectrometry, DNA sequencing, 03 medical and health sciences, DNA database, medicine, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Fusarium species complex, 030306 microbiology, medicine.disease, biology.organism_classification, 3. Good health, elongation factor, [SDV] Life Sciences [q-bio], Elongation factor, lcsh:Biology (General), Identification (biology)
Abstract: Fusarium spp. are widespread environmental fungi as well as pathogens that can affect plants, animals and humans. Yet the epidemiology of human fusariosis is still cloudy due to the rapidly evolving taxonomy. The Mass Spectrometry Identification database (MSI) has been developed since 2017 in order to allow a fast, accurate and free-access identification of fungi by matrix-assisted laser desorption ionization—time of flight (MALDI-TOF) mass spectrometry. Taking advantage of the MSI database user network, we aim to study the species distribution of Fusarium spp. isolates in an international multicenter prospective study. This study also allowed the assessment of the abilities of miscellaneous techniques to identify Fusarium isolates at the species level. The identification was performed by PCR-sequencing and phylogenic-tree approach. Both methods are used as gold standard for the evaluation of mass spectrometry. Identification at the species complex was satisfactory for all the tested methods. However, identification at the species level was more challenging and only 32% of the isolates were correctly identified with the National Center for Biotechnology Information (NCBI) DNA database, 20% with the Bruker MS database and 43% with the two MSI databases. Improvement of the mass spectrometry database is still needed to enable precise identification at the species level of any Fusarium isolates encountered either in human pathology or in the environment.
Published: 2021

28. Hospital outbreak of fluconazole-resistant

Author: Arnaud, Fekkar, Marion, Blaize, Adrien, Bouglé, Anne-Cécile, Normand, Audrey, Raoelina, Dimitri, Kornblum, Laure, Kamus, Renaud, Piarroux, and Sébastien, Imbert
Subjects: Epidemiology and Surveillance
Abstract: The worldwide emergence of multidrug-resistant pathogenic fungi is a threat to human health. At this very moment, an emergence of Candida parapsilosis isolates harboring a resistance to fluconazole, one of the most popular antifungal drugs, is being described in several countries. We seek to better understand the epidemiology, pathogenicity, and transmission of resistant Candida parapsilosis. Faced with an outbreak of invasive infections due to resistant isolates of C. parapsilosis, we performed a 7-year retrospective and prospective analysis of 283 C. parapsilosis isolates collected in 240 patients, among whom 111 had invasive candidiasis. The study included a review of hospital records, genotyping analysis, and susceptibility testing that allowed us to determine the type and outcome of infections, as well as the spatial and temporal spread of clusters. Overall, the incidence of azole resistance was 7.5%. Genotyping analysis unveiled several previously undetected outbreaks and clonal spread of susceptible and resistant isolates over a long period of time. In comparison with susceptible isolates, resistant ones have a more restricted genetic diversity and seem to be more likely to spread and more frequently associated with invasive infections. In intensive care units, patients with invasive infections due to resistant isolates had poorer outcomes (overall mortality at day 30 of 40%; 4/10) than susceptible ones (overall mortality at day 30 of 26.5%; 9/34). Our results suggest that the propensity of C. parapsilosis to spread in an epidemic fashion is underestimated, which warrants reinforced control and epidemiological survey of this species.
Published: 2021

29. Evaluation of the Chagas Western Blot IgG Assay for the Diagnosis of Chagas Disease

Author: S. Jauréguiberry, Margarita Bisio, Dominique Mazier, Ballering Griselda, Luc Paris, Julián Ernesto Nicolás Gulin, Jaime Altcheh, Jean-Yves Brossas, François-Xavier Lescure, Jeremy Guihenneuc, Arnaud Fekkar, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Microbiology (medical), Chagas disease, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Trypanosoma cruzi, 030231 tropical medicine, diagnostic, Article, Serology, 03 medical and health sciences, 0302 clinical medicine, Western blot, Antigen, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, parasitic diseases, medicine, Immunology and Allergy, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, 0303 health sciences, General Immunology and Microbiology, biology, medicine.diagnostic_test, 030306 microbiology, business.industry, biology.organism_classification, medicine.disease, Virology, 3. Good health, Blot, Infectious Diseases, Parasitology, biology.protein, Medicine, Antibody, business
Abstract: Chagas disease is a debilitating and often fatal pathology resulting from infection by the protozoan parasite Trypanosoma cruzi. In its recommendations, the World Health Organization states that the diagnosis of T. cruzi infection is usually based on the detection of antibodies against T. cruzi antigens and performed with two methodologically different assays. An inconclusive result can be resolved with a third “confirmatory” assay. The objective of this article is to evaluate the effectiveness of the Chagas Western Blot IgG assay (LDBio Diagnostics, Lyon, France) as a confirmatory serologic test. The Chagas Western Blot IgG assay was performed with native antigens derived from a T. cruzi strain of the TcVI genotype. Retrospective sera were provided by two parasitology laboratories (France and Argentina). The sensitivity, specificity, positive predictive value and negative predictive value of the Chagas blot were all 100% in our sera collection. The Chagas blot is an easy and qualitative method for the diagnosis of Chagas disease, with results in less than 2 h. This immunoblot has potential as a supplemental test for the confirmation of the presence of antibodies against T. cruzi in serum specimens. Nonetheless, the very good initial results presented here will need to be confirmed in larger studies.
Published: 2021

30. High Prevalence of Fungal Infections in Mechanically Ventilated COVID-19 Patients in the ICU: The French Multicenter MYCOVID Study

Author: Jean-Christophe Richard, Nicolas de Prost, Yves Cohen, Sylvie Paulus, Dorothée Quinio, Melek Manai, Carole Schwebel, Florence Persat, Antoine Berry, Cécile Garnaud, Lionel Lamhaut, Florian Reizine, Jordan Leroy, Hélène Guegan, Béatrice Riu-Poulenc, Jean Marc Tadie, Muriel Cornet, Antoine Monsel, Arnaud Fekkar, Guillaume Desoubeaux, Ferhat Meziani, Marie Soulié, Jean-Pierre Gangneux, Florence Robert-Gangneux, Nicolas Terzi, Mathieu Lesouhaitier, Yves Le Tulzo, Christine Bonnal, Bruno Mégarbane, Valérie Letscher-Bru, Guillaume Voiriot, Gilles Nevez, Brice Autier, Jean-François Timsit, Nadine François, Jean Menotti, Frederique Boquel, Patrice Le Pape, Christophe Hennequin, Xavier Iriart, Estelle Cateau, Charles Edouard Luyt, Francoise Botterel, Florent Wallet, Solène Le Gal, Philippe Seguin, Julien Mayaux, Jean-Ralph Zahar, Marie-Elisabeth Bougnoux, Bruno Laviolle, Estelle Sabourin, Sophie Brun, Jeff Morcet, Laurent Argaud, Juliette Guitard, Emmanuel Canet, Alexandre Alanio, Cécile Aubron, Saad Nseir, Florent Morio, Romain Pelletier, Marion Blaize, Damien Dupont, Ana Novara, Boualem Sendid, Stephan Ehrmann, Sandrine Houze, Eric Dannaoui, Sorya Belaz, and Arnaud W. Thille
Subjects: Mechanical ventilation, medicine.medical_specialty, High prevalence, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Emergency medicine, medicine, business, Dexamethasone, medicine.drug
Published: 2021

31. Hospital outbreak of fluconazole-resistant Candida parapsilosis: arguments for clonal transmission and long-term persistence

Author: Laure Kamus, Renaud Piarroux, Dimitri Kornblum, Anne-Cécile Normand, Arnaud Fekkar, Sébastien Imbert, Audrey Raoelina, Adrien Bouglé, Marion Blaize, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and HAL-SU, Gestionnaire
Subjects: medicine.medical_specialty, Candida parapsilosis, fungal outbreak, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Intensive care, Epidemiology, fluconazole, medicine, nosocomial infections, voriconazole, Pharmacology (medical), 030212 general & internal medicine, Genotyping, Candida, Pharmacology, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, 030306 microbiology, Transmission (medicine), Incidence (epidemiology), Outbreak, antifungal resistance, biology.organism_classification, Virology, candidiasis, 3. Good health, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Fluconazole, medicine.drug
Abstract: International audience; The worldwide emergence of multidrug-resistant pathogenic fungi is a threat to human health. At this very moment, an emergence of Candida parapsilosis isolates harbouring a resistance to fluconazole, one of the most popular antifungal drugs, is being described in several countries. We seek to better understanding the epidemiology, pathogenicity and transmission of resistant Candida parapsilosis Faced with an outbreak of invasive infections due to resistant isolates of C. parapsilosis, we performed a 7-year retrospective and prospective analysis of 283 C. parapsilosis isolates collected in 240 patients, among who 111 had invasive candidiasis. Study included review of hospital records, genotyping analysis and susceptibility testing that allow determining the type and outcome of infections, as well as the spatial and temporal spread of clusters. Overall the incidence of azole resistance was 7.5%. Genotyping analysis unveiled several previously undetected outbreaks and clonal spread of susceptible and resistant isolates over a long period of time. In comparison with susceptible isolates, resistant ones have a more restricted genetic diversity and seem to be more likely to spread and more frequently associated with invasive infections. In intensive care units, patients with invasive infections due to resistant isolates had poorer outcome (overall mortality at day 30 of 40%; 4/10) than susceptible ones (overall mortality at day 30 of 26.5%; 9/34). Our results suggest that the propensity of C. parapsilosis to spread on an epidemic fashion is underestimated, which warrants reinforced control and epidemiological survey of this species.
Published: 2021

32. MALDI-TOF-Based Identification of Dermatophytes

Author: Arnaud Fekkar, Alicia Moreno-Sabater, Renaud Piarroux, and Anne-Cécile Normand
Subjects: Computer science, Identification (biology), Computational biology, Mass spectrometry
Abstract: Dermatophytes and other keratinophilic fungi are common pathogens. Yet, their correct morphological identification remains a challenge for the mycologist. In the past few years, matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS) has become a widely used technique for pathogen identification in microbiology laboratories. The application of mass spectrometry for the identification of dermatophytes faces specific difficulties and benefits from a limited number of studies. In this chapter, we review the general principles of mass spectrometry and detail the technical aspects, such as sample preparation, type of targets, and scope of the different matrixes available. Various systems are currently available that use different basic spectrum processing and variable identification algorithms. We describe these different systems and the different databases available to date and their respective performance for the identification of dermatophytes and propose a review of the literature.
Published: 2021

33. Scedosporiosis/lomentosporiosis observational study (SOS): Clinical significance of Scedosporium species identification

Author: Boris Melloni, Benoit Roze, Lilia Hasseine, Jacques-Olivier Bay, Laurence Delhaes, Dominique Toubas, Gaelle Guillerm, Xavier Iriart, Thomas Similowski, Valérie Letscher-Bru, Liana Carausu, Adela Angoulvant, Eric Caumes, Marie-Elisabeth Bougnoux, Yves Leprince, Taieb Chouaki, Cécile Molucon-Chabrot, Eric Dannaoui, Hervé Dutronc, Youssef El-Samad, Florent Morio, Morgane Mourguet, Alexandre Alanio, Berengere Gruson, Pierre Cahen, Stéphane Ranque, Anne Boullié, Julie Bonhomme, Violaine Noel, Françoise Dromer, Elisabeth Chachaty, Felipe Suarez, Beate Heym, François Bissuel, Cécile Jensen, Jean-Pierre Gangneux, Emmanuelle Mouchon, Philippe Zann, Patricia Mariani, Bernard Bouteille, Véronique Leflon-Guibout, Dea Garcia-Hermoso, Anne Scemla, Stéphane Blanche, Agnes Lefort, Dorothée Raoux-Barbot, Didier Bronnimann, Olivier Lortholary, Matthieu Revest, Fanny Lanternier, Philippe Poirier, Luc Quaesaet, Marie Machouart, Françoise Botterel-Chartier, Viviane Queyrel-Moranne, Thomas Perpoint, Anne De Tinteniac, Pascale Penn, Ana Presedo, Marie Balsat, Anne Huynh, Lelia Escaut, Noémie Gadaud, Antoine Huguenin, Martine Gari-Toussaint, Sophie Brun, Jean-Marie Forel, Blandine Rammaert, Nicole Desbois, Alain Delmer, Valérie Moal, Arnaud Fekkar, Damien Hoinard, Elizabeth Rivaud, Delphine Lancement, Laurence Pougnet, Valérie Zeller, Jacques Grill, Florence Pasquier, Fabrice Larosa, Jean-François Papon, Nina Arakelyan-Laboure, Thomas Daix, Catherine Cordonnier, Nicolas Limal, Patrick Lutz, Laurence Maulin, Céline Nourrisson, Stéphane Bretagne, Françoise Uettwiller, Florence Ader, Céline Dieval, Nicolas Traversier, Sophie Bayle, Sorya Belaz, Frédéric Villega, Flore Sicre De Fontbrune, Didier Poisson, Olivier Moquet, Guillaume Martin-Blondel, Kamel Laribi, Delphine Horeau-Langlard, Gilles Nevez, Stéphanie Branger, Audrey Hessel, Philippe Herman, Jérémie Orain, Emilie Catherinot, Frédéric Mechai, Cristina Audoly, Frédéric Gabriel, Jean-François Velly, Caroline Fritz, Muriel Alvarez, Romain Guillemain, Pascal Turlure, Grégoire Leclerc, Frederic Pene, Lionel Mannone, Frédéric Grenouillet, Yoann Prevot, Louis-Jean Couderc, Isabelle Degasne, Giovanna Ingenuo, Joséphine Dorin, Florence Persat, Pierre-Marie Roger, Nathalie Brieu, David Boutoille, Pierre Frange, Nicolas Paleiron, Christophe Joubert, Laurent Hustache-Mathieu, Raoul Herbrecht, Frédéric Janvier, Lenaïg Le Clech, Cécile Gautier, Joelle Guitard, Nicolas Durrleman, Romain Guery, Stéphane De Botton, Sophie Cassaing, Marine Paul, Rachel Brault, Claire Briere-Bellier, Catherine Kauffmann-Lacroix, Nicolas Engrand, Audrey Berric, Hôpital Henri Mondor, Diane Bouvry, André Paugam, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Victor Segalen - Bordeaux 2, Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier du Pays d'Aix, CHU Amiens-Picardie, The National Reference Center for Invasive Mycoses and Antifungals is supported in part by Santé Publique France and Institut Pasteur., Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris], and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Male, medicine.medical_specialty, Antifungal Agents, Adolescent, LOMENTOSPORA PROLIFICANS, Lomentospora prolificans, Microbial Sensitivity Tests, Neutropenia, Scedosporium sp, Scedosporium, Young Adult, 03 medical and health sciences, Scedosporium species, Internal medicine, Humans, Medicine, Clinical significance, Child, Mycological Typing Techniques, scedosporiosis, Phylogeny, Fungemia, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Retrospective Studies, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, 030306 microbiology, business.industry, Infant, Newborn, Infant, Scedosporium apiospermum, General Medicine, Middle Aged, medicine.disease, cardiovascular localization, 3. Good health, Infectious Diseases, Child, Preschool, outcome, Female, Observational study, France, business, Invasive Fungal Infections
Abstract: International audience; Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes. We retrospectively studied cases of invasive scedosporiosis in France from 2005 through 2017 based on isolates characterized by polyphasic approach. We recorded 90 cases, mainly related to Scedosporium apiospermum (n = 48), S. boydii/S. ellipsoideum (n = 20), and Lomentospora prolificans (n = 14). One-third of infections were disseminated, with unexpectedly high rates of cerebral (41%) and cardiovascular (31%) involvement. In light of recent Scedosporium taxonomic revisions, we aimed to study the clinical significance of Scedosporium species identification and report for the first time contrasting clinical presentations between infections caused S. apiospermum, which were associated with malignancies and cutaneous involvement in disseminated infections, and infections caused by S. boydii, which were associated with solid organ transplantation, cerebral infections, fungemia, and early death. The clinical presentation of L. prolificans also differed from that of other species, involving more neutropenic patients, breakthrough infections, fungemia, and disseminated infections. Neutropenia, dissemination, and lack of antifungal prescription were all associated with 3-month mortality. Our data support the distinction between S. apiospermum and S. boydii and between L. prolificans and Scedosporium sp. Our results also underline the importance of the workup to assess dissemination, including cardiovascular system and brain. Lay Summary Scedosporiosis/lomentosporiosis is a devastating emerging fungal infection. Our objective was to describe the clinical pattern and to analyze whether taxonomic grouping of the species involved was supported by differences in terms of clinical presentations or outcomes.
Published: 2020

34. Neurological diseases of unknown etiology: Brain-biopsy diagnostic yields and safety

Author: Bertrand Mathon, Alexandre Le Joncour, Franck Bielle, Karima Mokhtari, Anne-Laure Boch, Matthieu Peyre, Zahir Amoura, Patrice Cacoub, Nadia Younan, Sophie Demeret, Eimad Shotar, Sonia Burrel, Arnaud Fekkar, Jérôme Robert, Aymeric Amelot, Marc Pineton de Chambrun, Alexandre Carpentier, Laurent Capelle, Soledad Navarro, Olivier Benveniste, Dimitri Psimaras, Khê Hoang-Xuan, Jean-Yves Delattre, Nicolas Weiss, Clémence Marois, Sarah Benghanem, Nadine Martin-Duverneuil, Véronique Leblond, Sylvain Choquet, Charles-Edouard Luyt, Alain Combes, Eric Caumes, Vincent Calvez, Aude Jary, Renaud Piarroux, Alexandra Aubry, Vincent Degos, Alice Jacquens, Caroline Papeix, Vincent Navarro, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de Neurochirurgie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Service de Neuropathologie [CHU Pitié Salpêtrière], Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière], Service de Médecine Interne 2, maladies auto-immunes et systémiques [CHU Pitié-Salpêtrière], Institut E3M [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut E3M [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC Pitié BT, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], Service de Neuroradiologie [CHU Pitié-Salpêtrière], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de virologie [CHU Pitié-Salpêtrière], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycobactéries et de la Résistance aux Antituberculeux [CHU Pitié-Salpêtrière], Service de Bactériologie et d'Hygiène Hospitalière [CHU Pitié-Salpêtrière], Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut E3M [CHU Pitié-Salpêtrière], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, Neurological morbidity, Biopsy, [SDV]Life Sciences [q-bio], Neurosurgery, Neuropathology, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Diagnostic workup, Histological diagnosis, Internal medicine, Internal Medicine, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Cryptogenic neurological disease, Retrospective Studies, medicine.diagnostic_test, business.industry, Brain biopsy, Brain, Retrospective cohort study, Odds ratio, 3. Good health, Brain lesion, Etiology, business
Abstract: International audience; Background: For nonneoplastic neurological diseases, no recommendation exists regarding the place or appropriate timing of brain biopsy. The aim of this study was to evaluate the diagnostic yield and safety of brain biopsies from patients with neurological diseases of unknown etiology.Methods: We performed a retrospective cohort study from January 1, 2008 to December 31, 2018. We analyzed 1847 brain-biopsied patients, including 178 biopsies indicated for neurological diseases of unknown etiology. Specific histological and final diagnosis rates, positive diagnosis-associated factors, complication rate and complication-associated factors were assessed.Results: Specific histological diagnosis and final diagnosis rates were 71.3% and 83.1%, respectively, leading to therapeutic management change(s) for 75.3% of patients. Brain- biopsy-related mortality and permanent neurological morbidity occurred in 1.1% and 0.6% of the patients, respectively. The multivariable logistic-regression model retained (odds ratio [95% CI] only immunodepression (2.2 [1.1-4.7]; P=.04) as being independently associated with specific histological diagnosis, while supratentorial biopsy-targeted lesions (4.1 [1.1-15.2]; P=.04) were independently associated with a final diagnosis. Biopsies obtained from comatose patients were less contributive to the diagnosis (0.2 [0.05-0.7]; P=.01). Prebiopsy platelet count
Published: 2020

35. Invasive Infections with Nannizziopsis obscura Species Complex in 9 Patients from West Africa, France, 2004–20201

Author: Sophie Brun, Blandine Denis, Elie Haddad, Maud Gits-Muselli, Valérie Vidal, Guy Galeazzi, Samia Hamane, Arnaud Fekkar, Rozenn Le Berre, Gilles Nevez, Arnaud Jabet, Stéphane Bretagne, Dea Garcia-Hermoso, Fanny Lanternier, Martin Siguier, Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Paris (UP), Hôpital Max Fourestier, Nanterre, Hôpital Hôtel-Dieu [Paris], Saint Joseph Medical Center [Beirut], Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], The National Reference Center for Invasive Mycoses and Antifungals is supported by the French Center for Diseases Control (Santé Publique France) and Institut Pasteur in Paris., Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Cité (UPCité), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Species complex, Nannizziopsis, Epidemiology, Antifungal drugs, 030231 tropical medicine, West africa, Microbiology, 03 medical and health sciences, 0302 clinical medicine, West Africa, 030212 general & internal medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, invasive fungal infections, biology, Onygenales, biology.organism_classification, 3. Good health, emergence and immunosuppression, Infectious Diseases, Etiology, France, fungi, Nannizziopsis obscura
Abstract: International audience; Nine new human invasive infections caused by the keratinophilic fungi Nannizziopsis obscura have been reported in France since 2004. The patients had variable clinical manifestations, had frequent dissemination, were mainly T-cell immunocompromised, and all originated from sub-Saharan West Africa. Before collection of the isolates, the etiologies of these infections were often misidentified, underscoring the extent of microscopic and cultural polymorphisms. All isolates but 1 had low MICs for the 8 antifungal drugs tested. When treated, patients received mainly azole therapy. Two of 7 patients with a known outcome died. We performed multilocus sequence analysis of N. obscura clinical strains and several strains of Nannizziopsis spp. isolated from reptiles. The human strains were clearly differentiated from the animal strains. N. obscura might be endemic to West Africa and responsible for undetected infections, which might become reactivated when immunosuppression occurs. N. obscura infection is probably underestimated because only sequencing enables proper identification.
Published: 2020

36. Species Distribution and Comparison between EUCAST and Gradient Concentration Strips Methods for Antifungal Susceptibility Testing of 112 Aspergillus Section Nigri Isolates

Author: Laurence Lachaud, B. Carrara, Sébastien Imbert, N. Zahr, P. Le Pape, Arnaud Fekkar, Stéphane Ranque, R. Richards, Milène Sasso, Renaud Piarroux, Anne-Cécile Normand, F. Morio, Danièle Maubon, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), and Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)
Subjects: Species complex, Veterinary medicine, Species distribution, 03 medical and health sciences, Common species, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, medicine, Pharmacology (medical), [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Pharmacology, chemistry.chemical_classification, 0303 health sciences, Aspergillus, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, biology, 030306 microbiology, Aspergillus niger, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Infectious Diseases, chemistry, Aspergillus tubingensis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Azole, medicine.drug
Abstract: Aspergillus niger, the third species responsible for invasive aspergillosis, has been considered as a homogeneous species until DNA-based identification uncovered many cryptic species. These species have been recently reclassified into the Aspergillus section Nigri However, little is yet known among the section Nigri about the species distribution and the antifungal susceptibility pattern of each cryptic species. A total of 112 clinical isolates collected from 5 teaching hospitals in France and phenotypically identified as A. niger were analyzed. Identification to the species level was carried out by nucleotide sequence analysis. The MICs of itraconazole, voriconazole, posaconazole, isavuconazole, and amphotericin B were determined by both the EUCAST and gradient concentration strip methods. Aspergillus tubingensis (n = 51, 45.5%) and Aspergillus welwitschiae (n = 50, 44.6%) were the most common species while A. niger accounted for only 6.3% (n = 7). The MICs of azole drugs were higher for A. tubingensis than for A. welwitschiae The MIC of amphotericin B was 2 mg/liter or less for all isolates. Importantly, MICs determined by EUCAST showed no correlation with those determined by the gradient concentration strip method, with the latter being lower than the former (Spearman's rank correlation tests ranging from 0.01 to 0.25 depending on the antifungal agent; P > 0.4). In conclusion, A. niger should be considered as a minority species in the section Nigri The differences in MICs between species for different azoles underline the importance of accurate identification. Significant divergences in the determination of MIC between EUCAST and the gradient concentration strip methods require further investigation.
Published: 2020

37. Invasive pulmonary fusariosis in an immunocompetent critically ill patient with severe COVID-19

Author: Arnaud Fekkar, C. Poignon, A. Lampros, Corinne Vezinet, M. Blaize, and Antoine Monsel
Subjects: Microbiology (medical), 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Critically ill, business.industry, Pulmonary Fusariosis, medicine.medical_treatment, General Medicine, medicine.disease, Article, Pneumonia, Infectious Diseases, Pandemic, Medicine, Intubation, Immunocompetence, business, Intensive care medicine
Published: 2020

38. Antifungal susceptibility testing practices in mycology laboratories in France, 2018

Author: E. Mazars, Jean-Pierre Gangneux, Isabelle Accoceberry, Valérie Letscher-Bru, B. Bouteille, O. Augereau, V. Risco-Castillo, Sophie Brun, Jean-Philippe Bouchara, Arnaud Fekkar, Jacques Guillot, E. Bailly, André Paugam, Y. Le Govic, R.-A. Lavergne, Taieb Chouaki, C. Angebault, Emilie Frealle, Damien Costa, Adela Angoulvant, J. Dorin, Florence Persat, P. Bourdeau, Eric Dannaoui, Céline Nourrisson, Julie Bonhomme, S. Larréché, K. Brunet, Françoise Foulet, L. Hasseine, Anne-Pauline Bellanger, Y. Senghor, Stéphane Ranque, A.-M. Camin-Ravenne, Marie Machouart, Juliette Guitard, N. Desbois, F. Bert, Françoise Botterel, Marie-Elisabeth Bougnoux, Laurence Lachaud, S. Le Gal, Sophie Cassaing, Milène Sasso, Marc Sautour, Boualem Sendid, A. Fiacre, Antoine Huguenin, C. Bonnal, M. Cornet, Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital universitaire Bichat, CHU Bordeaux [Bordeaux], Dynamic Microbiology - EA 7380 (DYNAMIC), École nationale vétérinaire - Alfort (ENVA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est (UPE)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Parasitologie-Mycologie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Génétique Quantitative et Evolution - Le Moulon (Génétique Végétale) (GQE-Le Moulon), AgroParisTech-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional d'Orléans (CHRO), Hôpital Universitaire de Tours, Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie-Mycologie (CHU d'Angers), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Biologie et Pathogénicité fongiques - Fungal Biology and Pathogenicity (BPF), Institut Pasteur [Paris] (IP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), CHU Limoges, Hôpital Avicenne [AP-HP], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Bigorre [Tarbes], Service de Parasitologie et Mycologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Picardie Jules Verne (UPJV), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), CHU Rouen, Normandie Université (NU), Service de Maladies Infectieuses et Tropicales [Fort-de-France, Martinique], CHU Fort de France-CHU de la Martinique [Fort de France]-Hôpital Pierre Zobda-Quitman [CHU de la Martinique], CHU de la Martinique [Fort de France], Service de Parasitologie-Mycologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Parasitologie-Mycologie [CHRU LIlle], Institut de Microbiologie [CHRU Lille], Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Pôle de Biologie Pathologie Génétique [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Ecologie du parasitisme - EA 3609 (ECOPA), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille, Droit et Santé, Service de Parasitologie-Mycologie [Rennes], Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CHU Saint-Antoine [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Centre Hospitalier Universitaire de Reims (CHU Reims), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Valenciennes, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), Laboratoire de Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA), Université Paris Diderot - Paris 7 (UPD7), Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Henri Mondor, Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), We are very grateful to Dominique Toubas for all the help she provided for the preparation and smooth running of our meeting. We also thank all our colleagues who participate to the meeting and discuss the results of the present survey., Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Research Group Dynamyc , EA 7380, EnvA (DynamYc), École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est (UPE), Institut Pasteur [Paris]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Centre Hospitalier de Bigorre (Tarbes), Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Univ. Grenoble Alpes, CNRS, CHU Grenoble Alpes, Grenoble INP*, TIMC-IMAG, Grenoble, France, EA3609, Laboratoire ECOPA, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Service de Parasitologie - Mycologie [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Fédératif de Biologie (IFB) - Hôpital Purpan, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA)
Subjects: Antifungal, Quality Control, medicine.medical_specialty, Susceptibility testing, Laboratory Proficiency Testing, Antifungal Agents, medicine.drug_class, Laboratory practice, Microbial Sensitivity Tests, Mycology, History, 21st Century, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Disk Diffusion Antimicrobial Tests, Drug Resistance, Fungal, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, medicine, Humans, Medical physics, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Antifungal susceptibility testing, Etest, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 030306 microbiology, Professional Practice, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, Geography, Mic values, MIC value interpretation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, France, Laboratories
Abstract: International audience; A survey of mycology laboratories for antifungal susceptibility testing (AFST) was undertaken in France in 2018, to better understand the difference in practices between the participating centers and to identify the difficulties they may encounter as well as eventual gaps with published standards and guidelines. The survey captured information from 45 mycology laboratories in France on how they perform AFST (number of strains tested, preferred method, technical and quality aspects, interpretation of the MIC values, reading and interpretation difficulties). Results indicated that 86% of respondents used Etest as AFST method, with a combination of one to seven antifungal agents tested. Most of the participating laboratories used similar technical parameters to perform their AFST method and a large majority used, as recommended, internal and external quality assessments. Almost all the participating mycology laboratories (98%) reported difficulties to interpret the MIC values, especially when no clinical breakpoints are available. The survey highlighted that the current AFST practices in France need homogenization, particularly for MIC reading and interpretation.
Published: 2020

39. Comparison of the MICs Obtained by Gradient Concentration Strip and EUCAST Methods for Four Azole Drugs and Amphotericin B against Azole-Susceptible and -Resistant Aspergillus Section Fumigati Clinical Isolates

Author: L Verdurme, Sarah Dellière, Françoise Botterel, Juliette Guitard, Eric Dannaoui, Marie-Elisabeth Bougnoux, Y. Senghor, Arnaud Fekkar, Jeanne Bigot, and Christophe Hennequin
Subjects: Pharmacology, Voriconazole, chemistry.chemical_classification, 0303 health sciences, Posaconazole, Serial dilution, 030306 microbiology, Itraconazole, Broth microdilution, Biology, bacterial infections and mycoses, biology.organism_classification, Microbiology, Aspergillus fumigatus, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, chemistry, Amphotericin B, parasitic diseases, medicine, Azole, Pharmacology (medical), 030212 general & internal medicine, medicine.drug
Abstract: Reference methods used to assess the drug susceptibilities of Aspergillus fumigatus isolates consisted of EUCAST and CLSI standardized broth microdilution techniques. Considering the increasing rate and the potential impact on the clinical outcome of azole resistance in A. fumigatus, more suitable techniques for routine testing are needed. The gradient concentration strip (GCS) method has been favorably evaluated for yeast testing. The aim of this study was to compare the CGS test with EUCAST broth microdilution for amphotericin B (AMB), posaconazole (PCZ), itraconazole (ITZ), voriconazole (VRZ), and isavuconazole (ISA). A total of 121 Aspergillus section Fumigati strains were collected, including 24 A. fumigatus sensu stricto strains that were resistant to at least one azole drug. MICs were determined using GCS and EUCAST methods. Essential agreement between the 2 methods was considered when MICs fell within ±1 dilution or ±2 dilutions of the 2-fold dilution scale. Categorical agreement was defined as the percentage of strains classified in the same category (susceptible, intermediate, or resistant) with both methods. Essential agreements with ±1 dilution and ±2 dilutions were 96.7, 93.4, 90.0, 89.3, and 95% and 100, 99.2, 100, 97.5, and 100% for AMB, PCZ, ITZ, VRZ, and ISA, respectively. Categorical agreements were 94.3, 86.1, 89.3, and 88.5% for AMB, PCZ, ITZ, and VRZ, respectively. Detection of resistance was missed with the GCS for one strain (4.1%) for PCZ and for 2 strains (8.3%) for ISA. Determination of ITZ MICs using the GCS allowed the detection of 91.7% of azole-resistant strains. The GCS test appears to be a valuable method for screening azole-resistant A. fumigatus clinical isolates.
Published: 2020

40. Ibrutinib induces multiple functional defects in the neutrophil response against Aspergillus fumigatus

Author: Natacha Menezes, Christophe Combadière, Alexandre Boissonnas, David Ghez, Carole Soussain, Veronique Leblond, Anaïs Portalier, Damien Blez, Marion Blaize, Arnaud Fekkar, Aïda Meghraoui-Kheddar, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut Gustave Roussy (IGR)
Subjects: Neutrophils, [SDV.CAN]Life Sciences [q-bio]/Cancer, Aspergillosis, Article, Aspergillus fumigatus, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Piperidines, Immunity, medicine, Bruton's tyrosine kinase, Humans, 030304 developmental biology, Complications in Hematology, 0303 health sciences, Innate immune system, biology, business.industry, Adenine, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, Hematology, Spores, Fungal, medicine.disease, biology.organism_classification, 3. Good health, Lymphoma, Respiratory burst, chemistry, Ibrutinib, Immunology, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, 030215 immunology
Abstract: International audience; The Bruton tyrosine kinase inhibitor ibrutinib has become a leading therapy against chronic lymphoid leukemia. Recently, ibrutinib has been associated with the occurrence of invasive fungal infections, in particular invasive aspergillosis. The mechanisms underlying the increased susceptibility to fungal infections associated with exposure to ibrutinib are currently unknown. Innate immunity, in particular polymer-phonuclear neutrophils, represents the cornerstone of anti-Aspergillus immunity; however, the potential impact of ibrutinib on neutrophils has been little studied. Our study investigated the response to Aspergillus fumigatus and neutrophil function in patients with chronic lymphoid leukemia or lymphoma, who were undergoing ibrutinib therapy. We studied the consequences of ibrutinib exposure on the functions and anti-Aspergillus responses of neutrophils obtained from healthy donors and 63 blood samples collected at different time points from 32 patients receiving ibrutinib for lymphoid malignancies. We used both flow cytometry and video-microscopy approaches to analyze neutrophils' cell surface molecule expression, cytokine production, oxidative burst, chemotaxis and killing activity against Aspergillus Ibrutinib is associated, both in vitro and in patients under treatment, with multiple functional defects in neutrophils, including decreased production of reactive oxygen species, impairment of their capacity to engulf Aspergillus and inability to efficiently kill germinating conidia. Our results demonstrate that ibrutinib-exposed neutrophils develop significant functional defects that impair their response against Aspergillus fumigatus, providing a plausible explanation for the emergence of invasive aspergillosis in ibrutinib-treated patients.
Published: 2020

41. Fungal Infection during COVID-19: Does Aspergillus Mean Secondary Invasive Aspergillosis?

Author: Arnaud Fekkar, Alexandre Lampros, Corentin Poignon, and Marion Blaize
Subjects: Pulmonary and Respiratory Medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, Critical Care and Intensive Care Medicine, Aspergillosis, Broncho-alveolar lavage, Aspergillus fumigatus, Microbiology, Betacoronavirus, Galactomannan, chemistry.chemical_compound, Correspondence, Humans, Medicine, Pandemics, Aspergillus, biology, SARS-CoV-2, business.industry, COVID-19, biology.organism_classification, medicine.disease, chemistry, Pulmonary Aspergillosis, Coronavirus Infections, business
Published: 2020

42. Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient

Author: Alexandre Demoule, Julien Mayaux, Anne-Geneviève Marcelin, Marion Blaize, Renaud Piarroux, Alexandre Lampros, Cécile Nabet, Marc Thellier, and Arnaud Fekkar
Subjects: Male, Pediatrics, Epidemiology, Expedited, medicine.medical_treatment, coronavirus, lcsh:Medicine, Disease, medicine.disease_cause, Aspergillosis, intensive care unit, law.invention, 0302 clinical medicine, law, aspergillosis, 030212 general & internal medicine, Coronavirus, Intensive care unit, Infectious Diseases, Aspergillus, coronavirus disease, Immunocompetence, Coronavirus Infections, severe acute respiratory syndrome coronavirus 2, Microbiology (medical), medicine.medical_specialty, Pneumonia, Viral, 030231 tropical medicine, macromolecular substances, mechanical ventilation, lcsh:Infectious and parasitic diseases, Betacoronavirus, 03 medical and health sciences, Research Letter, Fatal Invasive Aspergillosis and Coronavirus Disease in an Immunocompetent Patient, medicine, Humans, viruses, lcsh:RC109-216, fungal superinfection, Pandemics, Aged, SARS, Mechanical ventilation, business.industry, SARS-CoV-2, lcsh:R, COVID-19, medicine.disease, zoonoses, Pneumonia, Pulmonary Aspergillosis, fungi, business, Complication
Abstract: Invasive pulmonary aspergillosis is a complication in critically ill patients with acute respiratory distress syndrome, especially those with severe influenza pneumonia. We report a fatal case of invasive pulmonary aspergillosis in an immunocompetent patient in France who had severe coronavirus disease–associated pneumonia.
Published: 2020

43. Distinct paradoxical inflammatory reaction followed by postantiretroviral therapy immune reconstitution syndrome in cryptococcal meningitis

Author: Sébastien Imbert, H. Guillot, Arnaud Fekkar, Valérie Pourcher, Morgan Ollivier, Ruxandra Calin, and Antoine Gaillet
Subjects: medicine.diagnostic_test, business.industry, Immunology, Magnetic resonance imaging, 030204 cardiovascular system & hematology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Immune system, medicine, Immunology and Allergy, 030212 general & internal medicine, Young adult, business, Cryptococcal meningitis, Meningitis
Published: 2018

44. Invasive aspergillosis due to Aspergillus section Usti: a multicenter retrospective study

Author: Eléna Charpentier, Frédéric Gabriel, Frédéric Lamoth, Maria Aigner, Emmanouil Glampedakis, Michela Paolucci, Felix Bongomin, Malcolm Richardson, C. Bonnal, Russel Edward Lewis, Arnaud Fekkar, Christophe Hennequin, Stéphane Bretagne, Patrice Le Pape, Arnaud Riat, Reinhard Zbinden, Veronique Erard, Pierre-Yves Bochud, Marie-Elisabeth Bougnoux, Ahmet Çağkan İnkaya, Olga V Shadrivova, Sophie Brun, Nina Khanna, Dionysios Neofytos, Anne-Pauline Bellanger, Eric Dannaoui, Florent Morio, Peter W Schreiber, Sevtap Arikan-Akdagli, Mario Fernández-Ruiz, Alix T. Coste, Nikolai Klimko, Sophie Cassaing, Glampedakis E., Cassaing S., Fekkar A., Dannaoui E., Bougnoux M.-E., Bretagne S., Neofytos D., Schreiber P.W., Hennequin C., Morio F., Shadrivova O., Bongomin F., Fernandez-Ruiz M., Bellanger A.P., Arikan-Akdagli S., Erard V., Aigner M., Paolucci M., Khanna N., Charpentier E., Bonnal C., Brun S., Gabriel F., Riat A., Zbinden R., Le Pape P., Klimko N., Lewis R.E., Richardson M., Inkaya A.C., Coste A.T., Bochud P.-Y., Lamoth F., Hôpital Lausanne, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hop Univ Geneve, Serv Malad Infect, Geneva, Switzerland, Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Saint-Petersburg, University of Manchester [Manchester], Unit Infectious Diseases, Hospital 12 de Octubre, Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Ankara University School of Medicine [Turkey], University of Fribourg, Universität Innsbruck [Innsbruck], Department of Hematology and Oncology 'L. e A. Seragnoli', St. Orsola University Hospital, University Hospital Basel [Basel], Service de Parasitologie Mycologie[Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Parasitologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Bordeaux [Bordeaux], Hôpitaux Universitaire de Genève, Laboratoire de parasitologie et de mycologie médicale [CHU Nantes], Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, and Université de Lausanne (UNIL)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Posaconazole, Antifungal Agents, Aspergillosi, Aspergillus puniceus, 030106 microbiology, Aspergillus calidoustus, Aspergillus pseudodeflectus, Aspergillosis, 03 medical and health sciences, Aspergillus ustus, Retrospective Studie, Internal medicine, Amphotericin B, medicine, Antifungal Agent, Humans, Retrospective Studies, Voriconazole, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, ddc:616, business.industry, Mortality rate, Retrospective cohort study, Aspergillus insuetus, medicine.disease, Aspergillu, 3. Good health, 030104 developmental biology, Infectious Diseases, Aspergillus, business, Invasive Fungal Infections, medicine.drug, Human
Abstract: Background Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Methods Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Results Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. Conclusions Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.
Published: 2019

45. Multi-centric evaluation of the online MSI platform for the identification of cryptic and rare species of Aspergillus by MALDI-TOF

Author: Anne Cécile Normand, Christine Schuttler, Lise Kristensen, Lilia Hasseine, Frédéric Gabriel, Damien Costa, Dirk Stubbe, Marijke Hendrickx, Sébastien Imbert, Sophie Brun, Hélène Raberin, Renaud Piarroux, Laurence Lachaud, Arnaud Fekkar, C. Bonnal, Sophie Cassaing, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut d'Histoire de la Pensée Classique (IHPC), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), WHO Collaborating Center on Prevention and Treatment of Human Echinococcosis, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Université Pierre et Marie Curie - Paris 6 (UPMC), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, Microbiological Techniques, Species complex, Databases, Factual, [SDV]Life Sciences [q-bio], 030106 microbiology, Rare species, DNA sequencing, 03 medical and health sciences, Species level, Humans, species complex, Sensu stricto, mass spectrometry, Aspergillus species, Aspergillus, cryptic species, Internet, biology, Mass spectrometry, General Medicine, biology.organism_classification, 030104 developmental biology, Infectious Diseases, Evolutionary biology, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cryptic species, Taxonomy (biology)
Abstract: The taxonomy of Aspergillus species has recently been revolutionized with the introduction of cryptic species and section concepts. However, their species-level identification in routine laboratories remains a challenge. The aim of this study was to prospectively assess the identification accuracy of cryptic species of Aspergillus in various laboratories using the mass spectrometry identification (MSI) platform, an independent and freely accessible online mass spectrometry database. Over a 12-month period, when a select set of MSI users identified cryptic species, they were contacted and requested to send the isolates to our laboratory for sequence-based identification. Sequence and MSI identification results were then compared. During the study period, 5108 Aspergillus isolates were identified using MSI including 1477 (28.9%) cryptic species. A total of 245 isolates that corresponded to 56 cryptic species and 13 sections were randomly selected for DNA sequencing confirmation. Agreement between the two methods was 99.6% at the section level and 66.1% at the species level. However, almost all discrepancies (72/83, 86.7%) were misidentifications between closely related cryptic species belonging to the same section. Fifty-one isolates from noncryptic species were also identified, thus yielding 100% and 92.2% agreement at the section and species level, respectively. Although the MSI fungus database is a reliable tool to identify Aspergillus at the section level, the database still requires adjustment to correctly identify rare or cryptic species at the species level. Nevertheless, the application properly differentiated between cryptic and sensu stricto species in the same section, thus alerting on possible specific isolate characteristics.
Published: 2019

46. Multicentre study to determine the Etest epidemiological cut-off values of antifungal drugs in Candida spp. and Aspergillus fumigatus species complex

Author: Didier Dupont, Jean-Pierre Gangneux, Hélène Guegan, Laurence Lachaud, Milène Sasso, B. Bouteille, Sandrine Houzé, F. Persat, Laurence Delhaes, Damien Costa, Nathalie Bourgeois, Eric Dannaoui, Françoise Botterel, Sophie Cassaing, Loïc Favennec, E. Charpentier, Arnaud Fekkar, M. Salsé, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Bordeaux [Bordeaux], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Limoges, Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Hôpital Lapeyronie [Montpellier] (CHU), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA)
Subjects: 0301 basic medicine, Microbiology (medical), Epidemiological cut-off values, Antifungal Agents, Endpoint Determination, [SDV]Life Sciences [q-bio], 030106 microbiology, Microbial Sensitivity Tests, Candida parapsilosis, Microbiology, Candida tropicalis, 03 medical and health sciences, 0302 clinical medicine, Disk Diffusion Antimicrobial Tests, Drug Resistance, Fungal, Candida krusei, medicine, Humans, 030212 general & internal medicine, Candida albicans, Etest, ComputingMilieux_MISCELLANEOUS, Candida, Retrospective Studies, biology, Candida glabrata, business.industry, Candida lusitaniae, Aspergillus fumigatus, General Medicine, bacterial infections and mycoses, biology.organism_classification, 3. Good health, Infectious Diseases, Aspergillus, Mycoses, Anidulafungin, France, business, medicine.drug
Abstract: Objectives To determine the Etest-based epidemiological cut-off values (ECVs) for antifungal agents against the most frequent yeast and Aspergillus fumigatus species isolated in 12 French hospitals. Methods For each antifungal agent, the Etest MICs in yeast and A. fumigatus isolates from 12 French laboratories were retrospectively collected from 2004 to 2018. The ECVs were then calculated using the iterative statistical method with a 97.5% cut-off. Results Forty-eight Etest ECVs were determined for amphotericin B, caspofungin, micafungin, anidulafungin, fluconazole, voriconazole, posaconazole and itraconazole, after pooling and analysing the MICs of 9654 Candida albicans, 2939 Candida glabrata SC, 1458 Candida parapsilosis SC, 1148 Candida tropicalis, 575 Candida krusei, 518 Candida kefyr, 241 Candida lusitaniae, 131 Candida guilliermondii and 1526 Aspergillus fumigatus species complex isolates. These ECVs were 100% concordant (identical or within one two-fold dilution) with the previously reported Etest-based ECVs (when available), and they were concordant in 76.1% of cases with the Clinical and Laboratory Standards Institute ECVs and in 81.6% of cases with the European Committee on Antimicrobial Susceptibility Testing ECVs. Conclusions On the basis of these and other previous results, we recommend the determination of method-dependent ECVs. Etest ECVs should not be used instead of breakpoints, but may be useful to identify non-wild-type isolates with potential resistance to antifungal agents, and to indicate that an isolate may not respond as expected to the standard treatment.
Published: 2019

47. Biosynthesis of cell wall mannan in the conidium and the mycelium ofAspergillusfumigatus

Author: Yanan Zhao, Anne Beauvais, David S. Perlin, Marie-Christine Prévost, Rémi Beau, Thierry Fontaine, Vishukumar Aimanianda, Jean-Paul Latgé, Christine Henry, Pauline Robinet, Arnaud Fekkar, Christoph Heddergott, and Isabelle Mouyna
Subjects: 0301 basic medicine, biology, Immunology, Fungal genetics, Mannose, Mannosyltransferases, bacterial infections and mycoses, biology.organism_classification, Microbiology, Yeast, Aspergillus fumigatus, carbohydrates (lipids), Cell wall, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, Biochemistry, Virology, skin and connective tissue diseases, Mycelium, Mannan
Abstract: The galactomannan is a major cell wall molecule of Aspergillus fumigatus. This molecule is composed of a linear mannan with a repeating unit composed of four α1,6 and α1,2 linked mannose with side chains of galactofuran. To obtain a better understanding of the mannan biosynthesis in A. fumigatus, it was decided to undertake the successive deletion of the 11 genes which are putative orthologs of the mannosyltransferases responsible for establishing α1,6 and α1,2 mannose linkages in yeast. These deletions did not lead to a reduction of the mannan content of the cell wall of the mycelium of A. fumigatus. In contrast, the mannan content of the conidial cell wall was reduced and this reduction was associated with a partial disorganization of the cell wall leading to defects in conidial survival both in vitro and in vivo.
Published: 2016

48. Management of diabetic foot ulcers: a 25% lidocaine topical cream formulation design, physicochemical and microbiological assessments

Author: Antoine Faucheron, Arnaud Fekkar, Fadwa El Kouari, Léa Dupont, Hassane Sadou Yayé, P. Tilleul, and A. Bellanger
Subjects: Preservative, Skin barrier, Lidocaine, Chemistry, Pharmaceutical, Drug Compounding, Drug Storage, Skin Cream, Pain, Administration, Cutaneous, 030226 pharmacology & pharmacy, 03 medical and health sciences, 0302 clinical medicine, Drug Stability, medicine, Humans, 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, Anesthetics, Local, Adverse effect, Original Research, Local anaesthetic, business.industry, Temperature, Hydrogen-Ion Concentration, medicine.disease, Diabetic foot, Diabetic Foot, Topical cream, Tolerability, Anesthesia, business, medicine.drug
Abstract: Background Given the importance of surgical debridement in healing of diabetic foot ulcers, effective local anaesthesia is required to manage the related extreme pain. The pharmaceutical proprietary products currently available have low concentrations and do not exceed 5% w/w local anaesthetic. Objective Formulation design of a lidocaine cream of 25% and assessment of the intrinsic stability. Methods A cream pharmaceutical form was chosen for its ability to cross the skin barrier and effectively anaesthetise the skin. The choice of cream formula is based on changes in the size of the emulsions and resistance to physical stress. Stability tests were assessed over a 6-month period in terms of physical (evaluation of oil droplets), microbiological (germ count and identification, and preservative antimicrobial efficacy) and chemical parameters (content and pH). Results Under the study conditions, the drug product displayed good physicochemical and microbiological stability for 6 months at 20°C and 40°C, and no degradation product was detected. Due to the systemic adverse effects of lidocaine, the pH stability guarantee the drug product tolerance along with very weak systemic passage. Conclusions Given the good physicochemical and microbiological stability of the drug product over 6-month period, it has been made available to the clinical unit. An average of 250 patients per year benefit from the treatment with an excellent efficacy/tolerability ratio.
Published: 2018

49. Clinical and Biological Factors Associated With Recurrences of Severe Toxoplasmic Retinochoroiditis Confirmed by Aqueous Humor Analysis

Author: Alexandre Matet, Bahram Bodaghi, Nathalie Cassoux, Emmanuelle Champion, Valérie Touitou, Luc Paris, Céline Terrada, Phuc LeHoang, Christine Fardeau, and Arnaud Fekkar
Subjects: Adult, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Immunoblotting, Administration, Oral, Antibodies, Protozoan, Aqueous humor, Gastroenterology, Polymerase Chain Reaction, Retinal scars, Aqueous Humor, 03 medical and health sciences, Biological Factors, 0302 clinical medicine, Recurrence, Internal medicine, medicine, Retrospective analysis, Humans, Eye Infections, Parasitic, Infusions, Intravenous, Toxoplasmosis, Ocular, Glucocorticoids, 030304 developmental biology, Aged, Retrospective Studies, 0303 health sciences, business.industry, Retrospective cohort study, Immunosuppression, Eye infection, DNA, Protozoan, Middle Aged, medicine.disease, Toxoplasmosis, Ophthalmology, Chorioretinitis, 030221 ophthalmology & optometry, Shared frailty, Female, business, Toxoplasma, Follow-Up Studies
Abstract: To investigate clinical and biological factors influencing recurrences of severe toxoplasmic retinochoroiditis (TRC) confirmed by aqueous humor analysis.Retrospective case series.Retrospective analysis of 87 subjects with severe TRC, proven by positive Goldmann-Witmer coefficient (GWC), Toxoplasma gondii (T. gondii) immunoblot, or T. gondii-specific polymerase chain reaction (PCR) in aqueous humor. Cases with immunosuppression or retinal scars without previous recorded episode were excluded. Time-dependent, clinical, treatment-related, and biological factors were explored by univariate and multivariate shared frailty survival analyses.Among 44 included subjects (age, 40.4 ± 17.6 years; follow-up, 8.3 ± 2.7 years), 22 presented recurrences. There was 0.11 recurrence/patient/year and mean disease-free interval was 5.0 ± 2.9 years. The risk of recurrence was higher immediately after an episode (P.0001). Among recurrent cases, the risk of multiple recurrences was higher when the first recurrence occurred after longer disease-free intervals (P = .046). In univariate analysis, the recurrence risk declined with higher number of intense bands on aqueous T. gondii immunoblot (P = .006), and increased when venous vasculitis was present initially (P = .019). Multivariate analysis confirmed that eyes with more intense bands on immunoblot had fewer recurrences (P = .041). There was a near-significant risk elevation after pyrimethamine/azithromycin treatment (P = .078 and P = .054, univariate and multivariate). Intravenous corticosteroid administration, oral corticosteroid administration, aqueous GWC, and T. gondii PCR did not influence recurrences (P = .12, P = .10, P = .39, and P = .96, respectively).Recurrences of severe TRC are not random and may be influenced by clinical and biological factors possibly related to blood-retinal barrier alterations. These results may contribute to identifying biomarkers for TRC reactivation.
Published: 2018

50. Species Identification and In Vitro Antifungal Susceptibility of Aspergillus terreus Species Complex Clinical Isolates from a French Multicenter Study

Author: C. Bonnal, Sandrine Houzé, Sébastien Imbert, Christophe Hennequin, J. M. Costa, Isabelle Accoceberry, Juliette Guitard, Eric Dannaoui, Nathalie Bourgeois, Arnaud Fekkar, Françoise Botterel, Renaud Piarroux, Anne-Cécile Normand, Stéphane Ranque, Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Université Pierre et Marie Curie - Paris 6 (UPMC), STFC Rutherford Appleton Laboratory (RAL), Science and Technology Facilities Council (STFC), Services de Maladies Infectieuses et Tropicales [CHU Bichat], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service de Parasitologie Mycologie [AP-HP Hôpital Bichat - Claude Bernard], Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Service de cancérologie et radiothérapie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Hôpital Européen Georges Pompidou, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Parasitologie - Mycologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), and Laboratoire Chrono-environnement (UMR 6249) (LCE)
Subjects: 0301 basic medicine, Pharmacology, chemistry.chemical_classification, Aspergillus, Species complex, biology, Itraconazole, 030106 microbiology, Broth microdilution, biology.organism_classification, bacterial infections and mycoses, Microbiology, 03 medical and health sciences, Infectious Diseases, chemistry, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, medicine, Azole, Pharmacology (medical), Aspergillus terreus, Etest, medicine.drug
Abstract: Aspergillus section Terrei is a species complex currently comprised of 14 cryptic species whose prevalence in clinical samples as well as antifungal susceptibility are poorly known. The aims of this study were to investigate A. Terrei clinical isolates at the species level and to perform antifungal susceptibility analyses by reference and commercial methods. Eighty-two clinical A. Terrei isolates were collected from 8 French university hospitals. Molecular identification was performed by sequencing parts of beta-tubulin and calmodulin genes. MICs or minimum effective concentrations (MECs) were determined for 8 antifungal drugs using both EUCAST broth microdilution (BMD) methods and concentration gradient strips (CGS). Among the 79 A. Terrei isolates, A. terreus stricto sensu ( n = 61), A. citrinoterreus ( n = 13), A. hortai ( n = 3), and A. alabamensis ( n = 2) were identified. All strains had MICs of ≥1 mg/liter for amphotericin B, except for two isolates (both A. hortai ) that had MICs of 0.25 mg/liter. Four A. terreus isolates were resistant to at least one azole drug, including one with pan-azole resistance, yet no mutation in the CYP51A gene was found. All strains had low MECs for the three echinocandins. The essential agreements (EAs) between BMD and CGS were >90%, except for those of amphotericin B (79.7%) and itraconazole (73.4%). Isolates belonging to the A . section Terrei identified in clinical samples show wider species diversity beyond the known A. terreus sensu stricto . Azole resistance inside the section Terrei is uncommon and is not related to CYP51A mutations here. Finally, CGS is an interesting alternative for routine antifungal susceptibility testing.
Published: 2018

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