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442 results on '"Mycologie moléculaire"'

1. Multicenter Evaluation of the FilmArray Blood Culture Identification 2 Panel for Pathogen Detection in Bloodstream Infections

Author: François Caméléna, Gauthier Péan de Ponfilly, Hélène Pailhoriès, Lucas Bonzon, Alexandre Alanio, Thibaut Poncin, Matthieu Lafaurie, François Dépret, Emmanuel Cambau, Sylvain Godreuil, Rachel Chenouard, Alban Le Monnier, Hervé Jacquier, Béatrice Berçot, Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Groupe Hospitalier Paris Saint-Joseph (hpsj), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SFR UA 4208 Interactions Cellulaires et Applications Thérapeutiques (ICAT), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut de Biologie en Santé (PHB-IRIS) [CHU Angers] (IBS), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), 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), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Hôpital Lariboisière-Fernand-Widal [APHP], Université Paris-Saclay, Centre hospitalier Saint-Joseph [Paris], Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service de maladies infectieuses et tropicales [Saint-Louis], 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 Cité (UPCité), Hôpitaux Universitaires Saint-Louis, Lariboisière, Fernand-Widal, This study was supported by bioMérieux (Marcy L’Etoile, France), which providedconsumables. The funders had no role in study design, data collection and interpretation, ormanuscript preparation.F.C. received lecture fees from bioMérieux. F.D. received lecture fees from bioMérieuxand Sedana and grants from European Society of Intensive Care Medicine, Société Françaised’Anesthésie Reanimation, and the French Ministry of Research. A.A. received lecture feesand travel grants from Gilead Sciences and Pfizer and received grants from AgenceNationale de la Recherche. All other authors report no conflicts of interest., and bioMérieux (Marcy L’Etoile, France)European Society of Intensive Care MedicineSociété Française d’Anesthésie ReanimationFrench Ministry of Research. Gilead SciencesPfizerAgence Nationale de la Recherche
Subjects: Microbiology (medical), BCID2, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, FilmArray, Physiology, [SDV]Life Sciences [q-bio], bloodstream infection, MESH: Blood Culture, BSI, MESH: Gram-Positive Bacteria, sepsis, Biofire, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, resistance gene, MESH: Gram-Negative Bacteria, molecular diagnosis, Genetics, MESH: Bacteremia, MESH: Sepsis, rapid diagnosis, genotypic identification, MESH: Humans, General Immunology and Microbiology, Ecology, Cell Biology, MESH: Bacteria, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology
Abstract: International audience; The FilmArray Blood Culture Identification 2 panel (BCID2; bioMérieux) is a fully automated PCR-based assay for identifying bacteria, fungi, and bacterial resistance markers in positive blood cultures (BC) in about 1 h. In this multicenter study, we evaluated the performance of the BCID2 panel for pathogen detection in positive BC. Conventional culture and BCID2 were performed in parallel at four tertiary-care hospitals. We included 152 positive BC-130 monomicrobial and 22 polymicrobial cultures-in this analysis. The BCID2 assay correctly identified 90% (88/98) of Gram-negative and 89% (70/79) of Gram-positive bacteria. Five bacterial isolates targeted by the BCID2 panel and recovered from five positive BC, including three polymicrobial cultures, were missed by the BCID2 assay. Fifteen isolates were off-panel organisms, accounting for 8% (15/182) of the isolates obtained from BC. The mean positive percent agreement between the BCID2 assay and standard culture was 97% (95% confidence interval, 95 to 99%), with agreement ranging from 67% for Candida albicans to 100% for 17 targets included in the BCID2 panel. BCID2 also identified the blaCTX-M gene in seven BC, including one for which no extended-spectrum β-lactamase (ESBL)-producing isolate was obtained in culture. However, it failed to detect ESBL-encoding genes in three BC. Two of the 18 mecA/C genes detected by the BCID2 were not confirmed. No carbapenemase, mecA/C, or MREJ targets were detected. The median turnaround time was significantly shorter for BCID2 than for culture. The BCID2 panel may facilitate faster pathogen identification in bloodstream infections. IMPORTANCE Rapid molecular diagnosis combining the identification of pathogens and the detection of antibiotic resistance genes from positive blood cultures (BC) can improve the outcome for patients with bloodstream infections. The FilmArray BCID2 panel, an updated version of the original BCID, can detect 11 Gram-positive bacteria, 15 Gram-negative bacteria, 7 fungal pathogens, and 10 antimicrobial resistance genes directly from a positive BC. Here, we evaluated the real-life microbiological performance of the BCID2 assay in comparison to the results of standard methods used in routine practice at four tertiary care hospitals.
Published: 2023

2. Mainly Post-Transplant Factors Are Associated with Invasive Aspergillosis after Allogeneic Stem Cell Transplantation: A Study from the Surveillance des Aspergilloses Invasives en France and Société Francophone de Greffe de Moelle et de Thérapie Cellulaire

Author: Karine Sitbon, Regis Peffault de la Tour, Sylvie Bastuji-Garin, Olivier Lortholary, Stéphane Bretagne, Sébastien Maury, Catherine Cordonnier, Christine Robin, Nicole Raus, CCSD, Accord Elsevier, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Mycologie moléculaire - Molecular Mycology, Société Française de Greffe de Moelle et de Thérapie Cellulaire, Saint-Denis, France, 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), Paris Descartes University, Université Paris Descartes - Paris 5 (UPD5), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinical Epidemiology and Ageing : Geriatrie Soins Primaires et Santé Publique (CEpiA), The SAIF program was supported by acspecific grant from Institut de Veille Sanitaire, 94410, Saint-Maurice, France., The authors are grateful to the microbiology and clinical staff from the French Mycosis Study Group who actively participated in the SAIF network. They are also grateful to the clinicians and data managers of the Société Française de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC) centers who provided data for this study., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris]
Subjects: Adult, Male, medicine.medical_specialty, Neutropenia, medicine.medical_treatment, Graft vs Host Disease, Hematopoietic stem cell transplantation, Disease, Aspergillosis, 03 medical and health sciences, Invasive fungal infection, 0302 clinical medicine, Recurrence, Risk Factors, Internal medicine, medicine, Humans, Prospective Studies, Registries, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Societies, Medical, Retrospective Studies, Transplantation, business.industry, Hematopoietic Stem Cell Transplantation, Hematology, Middle Aged, Allografts, medicine.disease, Control subjects, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Post transplant, Allogeneic stem cell transplantation, 3. Good health, Europe, surgical procedures, operative, 030220 oncology & carcinogenesis, Acute Disease, Female, Stem cell, business, 030215 immunology
Abstract: International audience; Invasive aspergillosis (IA) occurs in up to 23% of allogeneic hematopoietic stem cell transplantation (HSCT) patients. Although transplant procedures have changed over time, more late cases of IA are being observed. The objective of this study was to identify the pre-and post-transplant factors of IA in a large cohort of HSCT patients mainly transplanted with reduced-intensity conditioning. This multicenter, case-control study was carried out using data collected between 2005 and 2010 by the Surveillance des Aspergilloses Invasives en France program (Institut Pasteur, Paris) and the European Society for Blood and Marrow Transplantation ProMISe registry. Four control subjects without IA were individually matched to each case based on the center, patient age, and year of the transplant. We identified 185 cases of probable and proven IA and 651 control subjects. The median date of IA after the transplant was 133 days, with 35 cases (19%) of early IA (before day 40), 33 cases (18%) of late IA (days 40 to 100), and 117 cases (63%) cases of very late IA (after day 100). In the multivariate analysis early IA was significantly associated with a lack of engraftment, whereas late and very late IA were significantly associated with more than grade II acute graft-versus-host disease (GVHD); very late IA was also significantly associated with relapse and secondary neutropenia. Two-thirds of IA cases occurred more than 100 days after HSCT with different risk factors from those occurring earlier. Prophylactic strategies should consider the specific risk factors for late and very late IA, especially GVHD, relapse after transplant, and secondary neutropenia.
Published: 2019

3. Different repartition of the cryptic species of black aspergilli according to the anatomical sites in human infections, in a French University hospital

Author: Sophie Touratier, Dea Garcia-Hermoso, Maud Gits-Muselli, Samia Hamane, Louise Bondeelle, Stéphane Bretagne, Blandine Denis, Elisa Cherpin, Benjamin Verillaud, Alexandre Alanio, 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), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Département Otorhinolaryngologie, Hôpital Lariboisière Saint-Louis Fernand Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Maladies infectieuses, Hopital Lariboisière Saint-Louis Fernand Widal, Assistance Publique-Hôpitaux de Paris (AP-HP), Service de pneumologie [Saint-Louis], 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 Cité (UPCité), Pharmacie, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), The authors thank all the clinicians who cared for the patients and all the laboratory staff and more specifically Cécile Gautier for technical assistance regarding culture of strains and MIC determinations. We are also indebted to Françoise Dromer for her helpful comments to the manuscript., AUGUSTE, Christèle, Institut Pasteur [Paris], Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP)
Subjects: Species complex, Veterinary medicine, otomycosis, Otomycosis, Aspergillosis, 03 medical and health sciences, Aspergillus welwitschiae, medicine, Animals, Humans, Ear canal, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, 0303 health sciences, Aspergillus, invasive aspergillosis, biology, 030306 microbiology, Aspergillus niger, General Medicine, medicine.disease, biology.organism_classification, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Hospitals, Infectious Diseases, Aspergillus vadensis, medicine.anatomical_structure, Aspergillus tubingensis, Black aspergilli
Abstract: Black aspergilli of the section Nigri are rarely differentiated at the species level when originating from human specimens. We wondered whether some cryptic species could be more frequently observed in some clinical entities. We analyzed the 198 black isolates consecutively collected from the external ear canal (EEC; n = 66), respiratory specimens (n = 99), and environment (n = 33). DNA was extracted and species identification was performed upon the partial calmodulin gene. We identified by decreasing frequency: Aspergillus welwitschiae (35.3%), Aspergillus tubingensis (34.3%), Aspergillus niger (17.2%), Aspergillus luchuensis (4%), Aspergillus aff. welwitschiae (3%), Aspergillus neoniger (2%), Aspergillus piperis (1.5%), Aspergillus japonicus (1.0%), Aspergillus vadensis (0.5%), and two Aspergillus tubingensis clade (1%). The distribution of the three main cryptic species was different between EEC and respiratory samples (P Lay summary We analyzed 198 black aspergilli isolates collected from different samples type to determine their species identification. We observe a different distribution of species between ear canal and respiratory samples (P
Published: 2021

4. Successful Terbinafine Treatment for Cutaneous Phaeohyphomycosis Caused by Trematosphaeria grisea in a Heart Transplanted Man: Case Report and Literature Review

Author: Dea Garcia-Hermoso, Emmanuelle Vermes, Frédéric Bastides, Victor Mercier, Louis Bernard, Guillaume Desoubeaux, Zaki El Baz, Emilie Marteau, Anne de Muret, Elodie Miquelestorena-Standley, Éric Bailly, Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut Pasteur [Paris] (IP), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), None., Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and AUGUSTE, Christèle
Subjects: Male, 0301 basic medicine, Septate, medicine.medical_specialty, Antifungal Agents, Veterinary (miscellaneous), 030106 microbiology, Applied Microbiology and Biotechnology, Microbiology, Lesion, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Ascomycota, medicine, Humans, Chronic infectious disease, Terbinafine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Therapeutic strategy, business.industry, Isavuconazole, medicine.disease, Dermatology, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Transplant Recipients, 3. Good health, Phaeohyphomycosis, Cutaneous Phaeohyphomycosis, Dematiaceous fungus, Heart Transplantation, Trematosphaeria grisea, medicine.symptom, business, Agronomy and Crop Science, TREMATOSPHAERIA GRISEA, medicine.drug
Abstract: International audience; Phaeohyphomycosis is a chronic infectious disease caused by dematiaceous fungi. It is characterized by the presence of pigmented septate mycelia within tissues. In the case of superficial infection, the lesion(s) chronically evolve(s) toward painless pseudo-tumor(s) of the soft parts. We report herein the original case of a heart transplanted man who exhibited phaeohyphomycosis of the left hand, with no mention of travels in endemic areas. Trematosphaeria grisea was identified as the causative agent, which is quite innovative since this species has been rather described in mycetoma. The antifungal treatment initially based on isavuconazole alone was not sufficient to cure the patient. In contrast, its association with local terbinafine ointment allowed total clinical improvement. This finding is unusual as diagnosis of phaeohyphomycosis caused by T. grisea is uncommon in nontropical countries, and as the outcome appeared successful by the means of add-on therapeutic strategy with terbinafine.
Published: 2020

5. Addition of Flucytosine to Fluconazole for the Treatment of Cryptococcal Meningitis in Africa: A Multicountry Cost-effectiveness Analysis

Author: Olivier Lortholary, Síle F. Molloy, Sokoine Kivuyo, Shabbar Jaffar, Lawrence Mwenge, Louis W. Niessen, Cecilia Kanyama, Angela Loyse, Elvis Temfack, Shabir Lakhi, Joseph N Jarvis, Tinevimbo Shiri, Peter Mwaba, Robert S. Heyderman, Mina C. Hosseinipour, Charles Kouanfack, Sayoki Mfinanga, Tao Chen, Duncan Chanda, Thomas S. Harrison, Adrienne K. Chan, Liverpool School of Tropical Medicine (LSTM), St George's, University of London, Zambart Health Economics Unit Lusaka, University Teaching Hospital (UTH), Lusaka, University Teaching Hospital [Lusaka] (UTH), Institute for Medical Research and Training, University of Teaching Lusaka, Department of Internal Medicine and Directorate of Research and Post-graduate Studies, Lusaka Apex Medical University, Zambia, University of Malawi, University College of London [London] (UCL), University of North Carolina Project-Malawi (UNC Project), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Hôpital Central de Yaoundé [Yaoundé], Université de Dschang, Hôpital Général de Douala, Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), National Institute for Medical Research - Muhimbili Research Centre (NIMR), Zomba Central Hospital Malawi, University of Toronto, London School of Hygiene and Tropical Medicine (LSHTM), Bostwana Harvard AIDS Institute Partneship Gaborone, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), This work was supported by grants to the Advancing Cryptococcal Meningitis Treatment for Africa trial from the Medical Research Council, United Kingdom (grant number 100504) and the French Agency for Research on AIDS and Viral Hepatitis (ANRS, grant number ANRS12275)., The authors thank all the patients and their families, Andrew Nunn, Halima Dawood, Andrew Kitua, and William Powderly for serving on the data and safety monitoring committee, and Graeme Meintjes, Calice Talom, Newton Kumwenda, and Maryline Bonnet for serving on the trial steering committee., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Microbiology (medical), medicine.medical_specialty, Antifungal Agents, Cost effectiveness, Cost-Benefit Analysis, flucytosine, Meningitis, Cryptococcal, Flucytosine, 03 medical and health sciences, 0302 clinical medicine, Pharmacotherapy, cryptococcal meningitis, Internal medicine, Amphotericin B, fluconazole, medicine, Humans, 030212 general & internal medicine, Articles and Commentaries, cost-effectiveness, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, health care economics and organizations, 0303 health sciences, treatment, 030306 microbiology, business.industry, Mortality rate, virus diseases, Cost-effectiveness analysis, Confidence interval, 3. Good health, respiratory tract diseases, Infectious Diseases, Africa, business, Fluconazole, medicine.drug
Abstract: Background Mortality from cryptococcal meningitis remains very high in Africa. In the Advancing Cryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosine (5FC) was as effective and less costly than 2 weeks of amphotericin-based regimens. However, many African settings treat with FLU monotherapy, and the cost-effectiveness of adding 5FC to FLU is uncertain. Methods The effectiveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian site. The effectiveness of FLU was derived from cohorts of consecutively enrolled patients, managed in respects other than drug therapy, as were participants in ACTA. FLU costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs. The cost-effectiveness of FLU+5FC vs FLU alone was measured as the incremental cost-effectiveness ratio (ICER). A probabilistic sensitivity analysis assessed uncertainties and a bivariate deterministic sensitivity analysis examined the impact of varying mortality and 5FC drug costs on the ICER. Results The mean costs per patient were US $847 (95% confidence interval [CI] $776–927) for FLU+5FC, and US $628 (95% CI $557–709) for FLU. The 10-week mortality rate was 35.1% (95% CI 28.9–41.7%) with FLU+5FC and 53.8% (95% CI 43.1–64.1%) with FLU. At the current 5FC price of US $1.30 per 500 mg tablet, the ICER of 5FC+FLU versus FLU alone was US $65 (95% CI $28–208) per life-year saved. Reducing the 5FC cost to between US $0.80 and US $0.40 per 500 mg resulted in an ICER between US $44 and US $28 per life-year saved. Conclusions The addition of 5FC to FLU is cost-effective for cryptococcal meningitis treatment in Africa and, if made available widely, could substantially reduce mortality rates among human immunodeficiency virus–infected persons in Africa., The combination of flucytosine plus fluconazole (FLU) is cost-effective, compared with the commonly used regimen of FLU monotherapy, for cryptococcal meningitis treatment in Africa, with an incremental cost-effectiveness ratio of US $65 per life-year saved at the current price.
Published: 2020

6. Recurrent episodes of Candidemia due to Candida glabrata, Candida tropicalis and Candida albicans with acquired echinocandin resistance

Author: Marine Grosset, Marie Desnos-Ollivier, Cendrine Godet, Catherine Kauffmann-Lacroix, France Cazenave-Roblot, Unité Maladies Infectieuses et tropicales [CHU Poitiers], Service de Médecine Interne, Maladies Infectieuses et Tropicales [CHU Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre hospitalier universitaire de Poitiers (CHU Poitiers), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Mrs. Anne Boullié and Catherine Blanc for technical assistance and PF-8-Genotyping of Pathogens and Public Health, Institut Pasteur for sequencing. Jeffrey Arsham, an American medical translator, reviewed the original English-language text., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]
Subjects: Echinocandin resistance, 0301 basic medicine, Tuberculosis, Echinocandin, Fks mutation, 030106 microbiology, Microbiology, Candida tropicalis, 03 medical and health sciences, medicine, Mixed infection, Endocarditis, Candida albicans, lcsh:QH301-705.5, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Multiresistance, lcsh:R5-920, biology, Candida glabrata, business.industry, Candidemia, bacterial infections and mycoses, medicine.disease, biology.organism_classification, Corpus albicans, 3. Good health, Infectious Diseases, lcsh:Biology (General), Candida spp, lcsh:Medicine (General), business, medicine.drug
Abstract: International audience; Mixed fungal infection and acquired echinocandin resistance of Candida spp. remain infrequent. In this study we have reported the case of a patient hospitalized for tuberculosis who experienced multiple infections due to three common Candida species (C. albicans, C. glabrata, C. tropicalis). Furthermore, consecutive isolates from blood cultures and heart valve were found resistant to azoles (C. tropicalis) and to echinocandin with either novel (C. tropicalis) or previously described (C. albicans) missense mutations in the Fks gene.
Published: 2016

7. Emerging mould infections: Get prepared to meet unexpected fungi in your patient

Author: Cécile Gautier, Dea Garcia-Hermoso, Alexandre Alanio, Sarah Dellière, Olga Rivero-Menendez, Ana Alastruey-Izquierdo, Université de Paris (UP), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Instituto de Salud Carlos III [Madrid] (ISC), Institut Pasteur [Paris], Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Johns Hopkins University (JHU), We thank Françoise Dromer and Stéphane Bretagne for their continuous support., Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: emerging fungi, MESH: Fungi, Modern medicine, medicine.medical_specialty, Antifungal Agents, Saksenaea, Communicable Diseases, Emerging, Hormographiella, Westerdykella, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Emergomyces, medicine, MESH: Immunocompromised Host, Humans, MESH: Communicable Diseases, Emerging, 030212 general & internal medicine, Intensive care medicine, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, Trametes, 0303 health sciences, MESH: Humans, biology, business.industry, 030306 microbiology, Fungi, Actinomucor, General Medicine, biology.organism_classification, MESH: Antifungal Agents, 3. Good health, invasive fungal disease, Apophysomyces, Rhytidhysteron, Infectious Diseases, Scopulariopsis, business, Invasive Fungal Infections, MESH: Invasive Fungal Infections
Abstract: Invasive fungal diseases are increasing issues in modern medicine, where the human immunodeficiency virus (HIV) pandemic and the wider use of immunosuppressive drugs generate an ever-growing number of immunocompromised patients with an increased susceptibility to uncommon fungal pathogens. In the past decade, new species have been reported as being responsible for disseminated and invasive fungal diseases in humans. Among them, the following genera are rare but seem emerging issues: Scopulariopsis, Hormographiella, Emergomyces, Westerdykella, Trametes, Actinomucor, Saksenaea, Apophysomyces, and Rhytidhysteron. Delay in diagnosis, which is often the case in these infections, jeopardizes patients’ prognosis and leads to increased mortality. Here we summarize the clinical and biological presentation and the key features to identify these emerging pathogens and we discuss the available antifungal classes to treat them. We focused on Pubmed to recover extensively reported human invasive cases and articles regarding the nine previously cited fungal organisms. Information concerning patient background, macroscopic and microscopic description and pictures of these fungal organisms, histological features in tissues, findings with commonly used antigen tests in practice, and hints on potential efficient antifungal classes were gathered. This review's purpose is to help clinical microbiologists and physicians to suspect, identify, diagnose, and treat newly encountered fungi in hospital settings.
Published: 2019

8. Evaluation of Mass Spectrometry-Based Detection of Panfungal Serum Disaccharide for Diagnosis of Invasive Fungal Infections: Results from a Collaborative Study Involving Six European Clinical Centers

Author: Daniel Poulain, Elena De Carolis, Boualem Sendid, Malgorzata Mikulska, Yann Guérardel, Alexandre Mery, Marjorie Cornu, Claudio Viscoli, Lauro Damonti, Nadine François, Maurizio Sanguinetti, Marie Titecat, Pierre-Yves Bochud, Valérie Letscher-Bru, Alexandre Alanio, Raoul Herbrecht, Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Ospedale Policlinico San Martino [Genoa], Institut de Parasitologie et de Pathologie Tropicale (IPPTS), Université de Strasbourg (UNISTRA), Fondazione 'Policlinico Universitario A. Gemelli' [Rome], Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Interface de Recherche Fondamentale et Appliquée en Cancérologie (IRFAC - Inserm U1113), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Paul Strauss : Centre Régional de Lutte contre le Cancer (CRLCC)-Fédération de Médecine Translationelle de Strasbourg (FMTS), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Guérardel, Yann, Laboratoire de parasitologie mycologie, Physiopathologie des candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Candidoses, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Istituto di Microbiologia, Università Cattolica del 'Sacro Cuore', Lille Inflammation Research International Center (LIRIC), Clinic of Gastroenterology, Department of Medicine, Università degli Studi di Verona, Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Inst Microbiol, Università Cattolica del Sacro Cuore, Infectious Diseases Division, University of Genoa (UNIGE), CHU Strasbourg, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Lille Inflammation Research International Center (LIRIC) - U995, Lille Inflammation Research International Center - U 995 [LIRIC], Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, CHU Lille, Inserm, Université de Strasbourg [UNISTRA], Istituto di Ricovero e Cura a Carattere Scientifico [IRCCS], Centre Hospitalier Universitaire Vaudois [Lausanne] [CHUV], Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Université Paris Diderot - Paris 7 [UPD7], Istituti di Ricovero e Cura a Carattere Scientifico [IRCCS], and Interface de Recherche Fondamentale et Appliquée en Cancérologie [IRFAC - Inserm U1113]
Subjects: Male, Disaccharide, Aspergillosis, Disaccharides, invasive fungal infection, Gastroenterology, Adult, Aged, Aged, 80 and over, Antigens, Fungal, Candidiasis, Europe, Female, Humans, Intersectoral Collaboration, Invasive Fungal Infections, Mannans, Mass Spectrometry, Middle Aged, Mucormycosis, Sensitivity and Specificity, Young Adult, invasive aspergillosis, invasive candidiasis, mass spectrometry, mucormycosis, serological diagnosis, chemistry.chemical_compound, 0302 clinical medicine, Medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, Mannan, Antigens, Fungal/blood, Aspergillosis/diagnosis, Candidiasis/diagnosis, Disaccharides/blood, Invasive Fungal Infections/blood, Invasive Fungal Infections/diagnosis, Mannans/blood, Mucormycosis/diagnosis, 0303 health sciences, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Invasive candidiasis, Control subjects, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Microbiology (medical), medicine.medical_specialty, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Mycology, 03 medical and health sciences, Galactomannan, Invasive aspergillosis, Invasive candidiasis, Invasive fungal infection, Mass spectrometry, Mucormycosis, Serological diagnosis, Internal medicine, Author Correction, 030306 microbiology, business.industry, Galactose, medicine.disease, chemistry, Bacteremia, business
Abstract: A mass spectrometry (MS) method that detects a serum disaccharide (DS) (MS-DS) was recently described for the diagnosis of invasive fungal infections (IFI). We carried out a European collaborative study to evaluate this assay., A mass spectrometry (MS) method that detects a serum disaccharide (DS) (MS-DS) was recently described for the diagnosis of invasive fungal infections (IFI). We carried out a European collaborative study to evaluate this assay. Patients with the following IFI were selected according to the availability of sera obtained at about the time that IFI was documented: invasive candidiasis (IC; n = 26 patients), invasive aspergillosis (IA; n = 19), and mucormycosis (MM; n = 23). Control sera originated from 20 neutropenic patients and 20 patients with bacteremia. MS-DS was carried out in blind manner for the diagnosis of IFI. A diagnosis of IC or IA was confirmed by detection of mannan (Man) or galactomannan (GM), respectively, associated with detection of (1,3)-β-d-glucan (BDG) in both infections. MM was detected by quantitative real-time PCR (qPCR). All tests discriminated sera from patients with IC from sera from control subjects with bacteremia (P ≤ 0.0009). For IC, the MS-DS sensitivity and specificity were 51% and 87%, respectively. MS-DS complemented the high specificity of Man monitoring. All tests discriminated sera from IA patients from sera from neutropenic controls (P ≤ 0.0009). For IA, MS-DS sensitivity and specificity were 64% and 95%, respectively. Only 13/36 serum samples from patients with MM were concordant by MS-DS and qPCR (6 were positive, and 7 were negative); 14 were positive by MS-DS alone. qPCR and MS-DS made a similar contribution to the diagnosis of MM. In patients undergoing long-term monitoring, the persistent circulation of serum disaccharide was observed, whereas DNA was detected only for a short period after initiation of treatment. MS-DS has an important role to play in the early diagnosis of IFI. Its panfungal nature and complementarity with other tests may justify its use in the management of IFI.
Published: 2019

9. Diversity of coelomycetous fungi in human infections: A 10-y experience of two European reference centres

Author: Garcia-Hermoso, Dea, Valenzuela-Lopez, Nicomedes, Rivero-Menendez, Olga, Alastruey-Izquierdo, Ana, Guarro, Josep, Cano-Lira, José, Stchigel, Alberto, French Mycoses Study Group, The, Institut Pasteur [Paris], Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Mycologie moléculaire - Molecular Mycology, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Universitat Rovira i Virgili, Universidad de Antofagasta, Instituto de Salud Carlos III [Madrid] (ISC), This work was supported by the Spanish Ministerio de Economía y Competitividad, grant CGL2017-88094-P.Olga Rivero-Menendez holds a fellowship from the Fondo de Investigaciones Sanitarias (grant FI14CIII/00025). Ana Alastruey-Izquierdo is supported by a research project from the Fondo de Investigación Sanitaria (FIS) (project PI16CIII/00035)., We thank Cécile Gautier (National Reference Center for invasive Mycoses and Antifungals [NRCMA]) for technical assistance., Members of the French Mycoses Study Group who contributed their clinical isolates to this study are as follows: Annecy (S. Bland), Bichat (C. Chochillon), Boulogne-Billancourt (N.Ait-Ammar), Caen (C. Duhamel), Clermont Ferrand (P.Poirier), Cochin (A. Paugam), Corbeil-Essones (D. Kubab), Guadeloupe (M. Nicolas), La Réunion (S. Picot), Lyon (A.L. Bienvenu), Martinique (N. Desbois), Nantes (F. Morio), Necker (M.E. Bougnoux), Nouvelle Calédonie (R. Goursaud), Pitié (A. Fekkar), Poitiers (C. Kauffmann), Quinze-Vingts (L. Merabet), Rouen (L. Favennec), Saint Etienne (H. Raberin), Saint-Louis (A. Alanio), Toulouse (S. Cassaing)., Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0106 biological sciences, MESH: Sequence Analysis, DNA, Antifungal Agents, Phoma, Coelomycetes, 01 natural sciences, chemistry.chemical_compound, RNA, Ribosomal, 28S, Cluster Analysis, Pleosporales, DNA, Fungal, MESH: Phylogeny, Phylogeny, Diaporthales, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, MESH: Microbial Sensitivity Tests, MESH: DNA, Ribosomal, biology, Medicopsis, Antifungal testing, 3. Good health, MESH: RNA, Ribosomal, 28S, Infectious Diseases, France, MESH: Fungi, Context (language use), Microbial Sensitivity Tests, DNA, Ribosomal, Microbiology, Mycosis, 03 medical and health sciences, MESH: Mycoses, Genetics, Colletotrichum, MESH: Spain, Humans, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH: Humans, Fungi, Sequence Analysis, DNA, biology.organism_classification, MESH: Antifungal Agents, MESH: Cluster Analysis, MESH: DNA, Fungal, MESH: France, Mycoses, chemistry, Spain, Didymellaceae, Caspofungin, 010606 plant biology & botany
Abstract: International audience; The coelomycetous fungi are difficult to properly identify from their phenotypic characterization and their role as etiologic agents of human infections is not clear. We studied the species distribution of these fungi among clinical isolates that had been collected and stored over a ten-year period in two European reference laboratories (France and Spain). We identified phenotypically and molecularly 97 isolates by sequencing the D1-D2 fragment of the 28S nrRNA (LSU) gene and we provided the in vitro antifungal susceptibility pattern of seven antifungals against 46 isolates. Species of the orders Pleosporales and Glomerellales were present in both collections, and Botryosphaeriales and Diaporthales only in the French one. The most prevalent species were Medicopsis romeroi, Neocucurbitaria keratinophila, Neocucurbitaria unguis-hominis and Paraconiothyrium cyclothyrioides, which had been recovered primarily from superficial tissues. The Didymellaceae was the most common family represented, with 27 isolates distributed into five genera. Most of the isolates tested were susceptible to antifungals, and only the geometric mean (GM) and minimal inhibitory concentration (MIC) values of itraconazole and caspofungin had higher values. This study provides a good picture of the great diversity of coelomycetous fungi in the European clinical context, and the basis for future studies on this interesting but neglected group of fungi.
Published: 2019

10. Perspectives on Scedosporium species and Lomentospora prolificans in lung transplantation: Results of an international practice survey from ESCMID fungal infection study group and study group for infections in compromised hosts, and European Confederation of Medical Mycology

Author: Rammaert, B., Puyade, M., Cornely, O. A., Seidel, D., Grossi, P., Husain, S., Picard, C., Lass-Florl, C., Manuel, O., Le Pavec, J., Lortholary, O., Nagel, C., Westall, G., Morrissey, O., Chambers, D., Eschertzhuber, S., Coussement, J., Knoop, C., Vos, R., Dupont, L., Dumonceaux, M., Campos, S. V., Kabbani, D., Cervera, C., Luong, M. -L., Blanchard, E., Senechal, A., Pavec, J. L., Brugiere, O., Boussaud, V., Guillemain, R., Bervar, J. -F., Claustre, J., Haloun, A., Hirschi, S., Reynaud, M., Kneidinger, N., Gottlieb, J., Roilides, E., Zarrinfar, H., Rosso, L., Morlacchi, L. C., Dell'Amore, A., Loy, M., Santos, C. O. D., Rello, J., Monforte, V., Martin-Gomez, M. T., Medrano, F. L., Fernandez-Ruiz, M., Sole, A., Cifrian, J. M., Neofytos, D., Mueller, N., Benden, C., Brill, A. K., Kiyan, E., Gould, K., Gkrania-Klotsas, E., David, M., Weigt, S., Kwak, E. J., Silveira, F., Hadjiliadis, D., Baddley, J., Danziger-Isakov, L., Bhorade, S., Ison, M., Wolfe, C., Aslam, S., Budem, M., Musetti, A., Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), University Hospital of Cologne [Cologne], Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases - CECAD [Cologne, Germany] (Institute for Genetics), University of Cologne, German Centre for Infection Research (DZIF), Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), University Health Network, Hôpital Foch [Suresnes], Leopold Franzens Universität Innsbruck - University of Innsbruck, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Centre Chirurgical Marie Lannelongue (CCML), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre Chirurgical Marie Lannelongue (CCML)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Université Paris-Sud - Paris 11 (UP11), Université Paris-Saclay, 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), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), The authors thank all the people who helped to collect mycological data and to contact transplant centers: Alejandro Mario Bertolotti (Buenos Aires, Argentina), Claire Heney (Brisbane, Australia), Carlota Montesinos (Brussels, Belgium), Katrien Lagrou (Leuven, Belgium), Youri Gluczynski (Yvoir, Belgium), Sandrine Houze (Paris, France), Eric Dannaoui (Paris, France), Florent Morio (Nantes, France), Murielle Cornet (Grenoble, France), Valérie Bru (Strasbourg, France), Stéphane Ranque (Marseille, France), Emilie Cardot (Suresnes, France), Ludwig Sedlacek (Hannover, Germany), Maurizio Sanguinetti (Roma, Italy), Ana Alastruey (Madrid, Spain), Konrad Muehlethaler (Bern, Switzerland), Kevin Alby (Philadelphia, USA), Malcom Richardson (Manchester, UK), the members of the ESCMID Fungal Infection Study Group (EFISG) and Study Group for Infections in Compromised Hosts (ESGICH) and European Confederation of Medical Mycology (ECMM) who helped to promote the study, Jeffrey Arsham for editing our original English language manuscript., The SCEDO‐LUNG collaborative group collected the data., University of Insubria, Varese, University of Innsbruck, Centre chirurgical Marie Lannelongue, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]
Subjects: Internationality, [SDV]Life Sciences [q-bio], invasive fungal disease, lomentosporiosis, scedosporiosis, solid organ transplantation, Ascomycota, Humans, Lung Transplantation, Mycoses, Prospective Studies, Respiratory Tract Infections, Scedosporium, Surveys and Questionnaires, Disease Management, Immunocompromised Host, MESH: Mycoses/epidemiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Mycoses/etiology, MESH: Surveys and Questionnaires, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Respiratory Tract Infections/etiology, MESH: Humans, MESH: Respiratory Tract Infections/microbiology, MESH: Scedosporium/isolation & purification, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Lung Transplantation/adverse effects, MESH: Prospective Studies, MESH: Disease Management, MESH: Internationality, MESH: Ascomycota/isolation & purification, MESH: Immunocompromised Host
Abstract: International audience; Background: Scedosporium species and Lomentospora prolificans (S/L) are the second most common causes of invasive mold infections following Aspergillus in lung transplant recipients.Methods: We assessed the current practices on management of S/L colonization/infection of the lower respiratory tract before and after lung transplantation in a large number of lung transplant centers through an international practice survey from October 2016 to March 2017.Results: A total of 51 respondents from 45 lung transplant centers (17 countries, 4 continents) answered the survey (response rate 58%). S/L colonization was estimated to be detected in candidates by 48% of centers. Only 18% of the centers used a specific medium to detect S/L colonization. Scedosporium spp. colonization was a contraindication to transplantation in 10% of centers whereas L prolificans was a contraindication in 31%; 22% of centers declared having had 1-5 recipients infected with S/L in the past 5 years.Conclusions: This survey gives an overview of the current practices regarding S/L colonization and infection in lung transplant centers worldwide and underscores the need of S/L culture procedure standardization before implementing prospective studies.
Published: 2019

11. Variation in copy number of the 28S rDNA of Aspergillus fumigatus measured by droplet digital PCR and analog quantitative real-time PCR

Author: Nicolas Guigue, Marion Benabou, Alexandre Alanio, Stéphane Bretagne, Aude Sturny-Leclère, Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), Mycologie moléculaire, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: 0301 basic medicine, Microbiology (medical), DNA Copy Number Variations, [SDV]Life Sciences [q-bio], 030106 microbiology, Pcr assay, rDNA, Biology, Real-Time Polymerase Chain Reaction, Aspergillosis, DNA, Ribosomal, Sensitivity and Specificity, Microbiology, Genome, Real-time quantitative PCR, Aspergillus fumigatus, 03 medical and health sciences, RNA, Ribosomal, 28S, medicine, Humans, Digital polymerase chain reaction, Copy-number variation, Molecular Biology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, copy number variation, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, biology.organism_classification, Molecular biology, 030104 developmental biology, Real-time polymerase chain reaction, Quantitative Real Time PCR, Droplet digital PCR
Abstract: International audience; Droplet digital PCR (ddPCR) after DNA digestion yielded a 28S rDNA copy number of 61 to 86 copies/genome when testing 10 unrelated Aspergillus fumigatus isolates, higher than with quantitative PCR. Unfortunately, ddPCR after DNA digestion did not improve the sensitivity of our PCR assay when testing serum patients with invasive aspergillosis.
Published: 2016

12. Population Structure of Candida parapsilosis: No Genetic Difference Between French and Uruguayan Isolates Using Microsatellite Length Polymorphism

Author: Françoise Dromer, Marie Desnos-Ollivier, Victoria Bórmida, Philippe Poirier, Stéphane Bretagne, Céline Nourrisson, Dinorah Pan, Andrès Puime, Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Ministerio de salud publica, Unidad de Parasitologia y Micologia, Montevideo, Uruguay, Universidad de Montevideo, CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), 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), The YEASTS program was supported in part by Institut de Veille Sanitaire/Santé Publique France, and Institut Pasteur. This work was partially supported by grants from the Uruguayan Agency for Innovation and Research (ANII_FSS_2009_1721, ANII_POS_2011_1_3472) and French Embassy in Uruguay/Amsud Pasteur. The funders had no role in study design, data collection, analysis or interpretation of data., Institut Pasteur [Paris] (IP), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut national de recherches archéologiques préventives (Inrap), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Service de parasitologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Mycologie moléculaire, Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie et Mycologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Hôpital Saint-Louis, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)
Subjects: 0301 basic medicine, Candida parapsilosis, Genotype, Genotyping Techniques, Veterinary (miscellaneous), [SDV]Life Sciences [q-bio], 030106 microbiology, Population, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Population structure, Applied Microbiology and Biotechnology, Microbiology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, Polymorphism (computer science), Humans, education, Mycological Typing Techniques, Microsatellites genotyping, Genotyping, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Genetics, Candida parapsilosis Microsatellites genotyping Azoles resistance Candidemia Population structure, education.field_of_study, Genetic diversity, Molecular Epidemiology, biology, Outbreak, Genetic Variation, Candidemia, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Microsatellite, Uruguay, Azoles resistance, France, Agronomy and Crop Science, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Microsatellite Repeats
Abstract: International audience; Candida parapsilosis is a human commensal yeast, frequently involved in infection worldwide and especially in neonates. It is the second species responsible for bloodstream infections in Uruguay and the third species in France. We were interested in knowing whether the population structure of isolates responsible for candidemia in France and in Uruguay was different. Genotyping methods based on microsatellite length polymorphism (MLP) have been described and are especially used for investigation of local outbreaks. We therefore determined the genotypes of 159 C. parapsilosis isolates recovered from 122 patients (84 French patients from 43 hospitals and 38 Uruguayan patients from 10 hospitals) using three microsatellites markers previously described. Our results confirmed that C. parapsilosis population has a high genetic diversity, clonal inheritance and that majority of patients were infected by a single isolate. But we described recurrent infections due to related or unrelated genotypes resulting from isolates harboring loss or gain of heterozygosity. We also described three cases of coinfections due to unrelated genotypes. We did not uncover geographic specificity but observed two linked genotypes that seem to be associated with voriconazole resistance. Finally, among eight isolates involved in grouped cases, the genotypes were similar in six cases supporting the hypothesis of inter-patient transmission. These results confirmed the usefulness of performing MLP genotyping analysis for grouped cases of C. parapsilosis isolates in order to reinforce preventive hygiene measures.
Published: 2018

13. Impact of echinocandin on prognosis of proven invasive candidiasis in ICU: a post-hoc causal inference model using the AMARCAND2 study

Author: Olivier Lortholary, Demory, Gouin, Tellier, Saliba, Cabaret, Karoubi, Diconne, Houissa, Carpentier, Hraiech, Mateu, Bretonnière, Cousson, Zogheib, Cinotti, Montcriol, Gally, Gette, Quinart, Lamhaut, Bonadona, Argaud, Jean-Pierre Gangneux, Angel, Thevenot, Ruiz, Van Grunderbeek, Chabanne, Ammenouche, Merle, Kherchache, Mira, Constantin, Guelon, Schmitt, Lepape, Brocas, Luyt, Elie Azoulay, Jung, Megarbane, Dubost, Grossmith, Gaudard, Hssain Aait, Kaidomar, Mootien, Perrigault, Badetti, Lemaire, Brua, Roquilly, Sejourne, Blasco, Allaouchiche, Bruder, Quintard, Seguin, Brunin, Lesieur, Wiramus, Lambiotte, Mahul, Vincent, Cerf, Delpierre, Tonnelier, Didier Guillemot, Bastien, Cheval, Dumenil, Mahe, Jean-Paul Mira, Plantefeve, Geffe, Guerin-Robardey, Navellou, Bollaert, Charles, Hervé Dupont, Lepoivre, Durand, D. du Cheyron, Forel, Jean-François Timsit, Gergaud, Lebreton, Baudin, Pierre-François Perrigault, Launoy, Hayl-Slayman, Baldesi, Foucher-Lezla, Ichai, Jean-Michel Constantin, Olivier Leroy, Girault, Goubaux, Sébastien Bailly, Barthet, Bellec, Duroy, Lefrant, Petitpas, Hilbert, Leroy, Guervilly, Samba, Adda, Philippe Montravers, Ragonnet, Fratea, Cohen, Ouattara, Grenot, Cartier, 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), Hôpital Chatiliez, Medical ICU, 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), Service d'anesthésie - réanimation chirurgicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Service d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Amiens-Picardie, Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-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 National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Service de médecine d'urgence [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], Hôpital Bichat - Claude Bernard, This work was supported by a grant from MSD France. The analysis was conducted independently by the AmarCAND2 Scientific Committee., Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département anesthésie et réanimation, CHU Clermont-Ferrand-Hôpital d'Estaing, Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses ( B2PHI ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], and Jonchère, Laurent
Subjects: 0301 basic medicine, Microbiology (medical), Azoles, Male, medicine.medical_specialty, Antifungal Agents, Echinocandin, 030106 microbiology, 03 medical and health sciences, Echinocandins, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Internal medicine, medicine, polycyclic compounds, Humans, Candidiasis, Invasive, 030212 general & internal medicine, Prospective Studies, Aged, Candida, Septic shock, business.industry, Confounding, Candidiasis, [ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Invasive candidiasis, Middle Aged, medicine.disease, Prognosis, bacterial infections and mycoses, 3. Good health, Surgery, Intensive Care Units, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Causal inference, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Cohort, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Female, business, Fluconazole, medicine.drug
Abstract: International audience; Objective: guidelines recommend first-line systemic antifungal therapy (SAT) with echinocandins in invasive candidiasis (IC), especially in critically ill patients. This study aimed at assessing the impact of echinocandins compared to azoles as initial SAT on the 28-day prognosis in adult ICU patients.Methods: From the prospective multicenter AmarCAND2 cohort (835 patients), we selected those with documented IC and treated with echinocandins (ECH) or azoles (AZO). The average causal effect of echinocandins on 28-day mortality was assessed using an inverse probability of treatment weight (IPTW) estimator.Results: 397 patients were selected, treated with echinocandins (242 patients, 61%) or azoles (155 patients, 39%); septic shock: 179 patients (45%). The median SAPSII was higher in the ECH group (48 [35; 62] vs. 43 [31; 58], p = 0.01). Crude mortality was 34% (ECH group) vs. 25% (AZO group). After adjustment on baseline confounders, no significant association emerged between initial SAT with echinocandins and 28-day mortality (HR: 0.95; 95% CI: [0.60; 1.49]; p = 0.82). However, echinocandin tended to benefit patients with septic shock (HR: 0.46 [0.19; 1.07]; p = 0.07).Conclusion: Patients who received echinocandins were more severely ill. Echinocandin use was associated with a non-significant 7% decrease of 28-day mortality and a trend to a beneficial effect for patient with septic shock.
Published: 2017

14. Antifungal therapy for patients with proven or suspected Candida peritonitis: Amarcand2, a prospective cohort study in French intensive care units

Author: Alexandre Ouattara, Lionel Lamhaut, Olivier Leroy, F. Thevenot, B. Goubaux, Franck Petitpas, Elie Azoulay, Cédric Bretonnière, P. Geffe, Jean-Marie Forel, Joel Cousson, G. Brunin, F. Bellec, Yves Cohen, A. Kherchache, C. Sejourne, R. Grenot, Bruno Mégarbane, A.L. Foucher-Lezla, Philippe Karoubi, M.C. Barthet, E. Duroy, Jean-Michel Constantin, S. Brua, F. Lebreton, Philippe Mateu, Anne Charlotte Tellier, Jean-Paul Mira, Didier Guillemot, T. Lepoivre, D. Guelon, Didier Demory, A.M. Guerin-Robardey, Elie Zogheib, D. Hayl-Slayman, Bernard Allaouchiche, Gilles Blasco, Pierre-François Perrigault, Bruno Levy, D. du Cheyron, Alain Lepape, J. F. Timsit, Nicolas Bruder, Michel Durand, N. Van Grunderbeek, Jean-Pierre Gangneux, H. Houissa, J.F. Vincent, E. Diconne, O. Lortholary, B Ragonnet, Christophe Lemaire, E. Brocas, Olivier Baldesi, E. Delpierre, Sébastien Bailly, J. Ruiz, Philippe Montravers, Hervé Dupont, Anne-Sylvie Dumenil, Olivier Lesieur, Agnès Bonadona, P. Cabaret, Philippe Gaudard, Ambroise Montcriol, P. Ichai, Z. Schmitt, C. Bensoussan, P. Gouin, Laurent Argaud, C. Dubost, Florent Baudin, Sami Hraiech, Christophe Guervilly, Pierre-Emmanuel Charles, Fabien Lambiotte, S. Gette, N. Ammenouche, M. Adda, Jean-Marie Tonnelier, D. Samba, Russel Chabanne, Pierre-Joachim Mahe, B. Page, P. Mahul, Dorothée Carpentier, Philippe Seguin, C. Badetti, J. Gally, Jean-Charles Cartier, Christophe Girault, S. Fratea, G. Angel, Olivier Bastien, Raphaël Cinotti, Charles-Edouard Luyt, Soizic Gergaud, Boris Jung, G. Grossmith, F. Saliba, Antoine Roquilly, C. Cheval, J.Y. Lefrant, A. Launoy, A. Aait Hssain, Gilles Hilbert, Sandrine Wiramus, Pierre-Edouard Bollaert, Hervé Quintard, Gaëtan Plantefève, Jean-Christophe Navellou, M. Kaidomar, A. Quinart, Charles Cerf, J.C. Merle, Y. Mootien, Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Université Paris Diderot - Paris 7 (UPD7)-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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Université Paris Diderot - Paris 7 (UPD7), Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Hôpital Chatiliez, Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses (B2PHI), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Clermont-Ferrand, CHU Amiens-Picardie, Service d'anesthésie - réanimation chirurgicale, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université Paris Diderot - Paris 7 ( UPD7 ), CHU Cochin [AP-HP], Université Paris Descartes - Paris 5 ( UPD5 ), Centre d'infectiologie Necker-Pasteur, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Biostatistique, Biomathématique, Pharmacoépidémiologie et Maladies Infectieuses ( B2PHI ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut Pasteur [Paris], and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: 0301 basic medicine, Comorbidity, Severity of Illness Index, 0302 clinical medicine, Critically ill patients, Risk Factors, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Peritonitis score, Odds Ratio, Prospective Studies, 030212 general & internal medicine, Simplified Acute Physiology Score, Prospective cohort study, Candida, biology, Candidiasis, General Medicine, Middle Aged, 3. Good health, Invasive candidiasis, Intensive Care Units, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, SAPS II, France, medicine.drug, Microbiology (medical), medicine.medical_specialty, Echinocandin, 030106 microbiology, Peritonitis, Empiric antifungal therapy, 03 medical and health sciences, Candida score, Internal medicine, Intensive care, medicine, Humans, Targeted antifungal therapy, Antifungal agents, Aged, Candida glabrata, business.industry, biology.organism_classification, medicine.disease, Surgery, Candida peritonitis, ROC Curve, business, Fluconazole
Abstract: International audience; OBJECTIVE:The clinical characteristics and prognosis of patients treated for Candida peritonitis (CP) were compared according to the type of systemic antifungal therapy (SAT), empiric (EAF) or targeted (TAF) therapies, and the final diagnosis of infection.METHODS:Patients in intensive care units (ICU) treated for CP were selected among the AmarCAND2 cohort, to compare patients receiving EAF for unconfirmed suspicion of CP (EAF/nonCP), to those with suspected secondarily confirmed CP (EAF/CP), or with primarily proven CP receiving TAF.RESULTS:In all, 279 patients were evaluated (43.4% EAF/nonCP, 29.7% EAF/CP and 25.8% TAF patients). At SAT initiation, the severity of illness was similar among EAF/nonCP and EAF/CP patients, lower among TAF patients (median Simplified Acute Physiology Score II (SAPS II) 49 and 51 versus 35, respectively; p 0.001). Candida albicans was involved in 67%, Candida glabrata in 15.6%. All strains were susceptible to echinocandin; 84% to fluconazole. Echinocandin was administered to 51.2% EAF/nonCP, 49% EAF/CP and 40% TAF patients. At day 28, 72%, 76% and 75% of EAF/nonCP, EAF/CP and TAF patients, respectively, were alive. An increased mortality was observed in patients with a Sequential Organ Failure Assessment (SOFA) score
Published: 2017

15. ESCMID and ECMM Joint Clinical Guidelines for the Diagnosis and Management of Mucormycosis 2013

Author: Arunaloke Chakrabarti, Emmanuel Roilides, Anuradha Chowdhary, Tomáš Freiberger, Maiken Cavling Arendrup, Josep Guarro, Murat Akova, O. Lortholary, Andrew J. Ullmann, Elizabeth M. Johnson, Joseph Meletiadis, Cornelia Lass-Flörl, Andreas H. Groll, S. de Hoog, S. Arikan-Akdagli, Jacques F. Meis, Anna Skiada, Manuel Cuenca-Estrella, Paul E. Verweij, Teun Boekhout, Jesús Guinea, Fanny Lanternier, Malcolm Richardson, Patricia Muñoz, Anna Maria Tortorano, Oliver A. Cornely, William W. Hope, Shallu Kathuria, Michaela Lackner, George Petrikkos, A.D. van Diepeningen, Livio Pagano, Eric Dannaoui, Katrien Lagrou, Evolutionary Biology (IBED, FNWI), University of Cologne, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, 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), Université Paris Descartes - Paris 5 (UPD5), Leuven University Hospital, Institute of Post Graduate Medical Education & Research [Calcutta] (IPGMER), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), National and Kapodistrian University of Athens (NKUA), CBS-KNAW Fungal Biodiversity Centre, Shanghai Institute of Medical Mycology, Changzheng Hospital, Second Military Medical University, University of Delhi, Instituto de Salud Carlos III [Madrid] (ISC), Masaryk University [Brno] (MUNI), Universitat Rovira i Virgili, and Centre National de la Recherche Scientifique (CNRS)
Subjects: Microbiology (medical), Posaconazole, medicine.medical_specialty, Antifungal Agents, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Aspergillosis, Amphotericin B, Amphotericin B deoxycholate, Internal medicine, Diagnosis, medicine, Humans, Mucormycosis, Intensive care medicine, treatment, business.industry, fungal infection, Deferasirox, mycosis, zygomycosis, General Medicine, medicine.disease, Clinical trial, Transplantation, Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], prophylaxis, business, guideline, medicine.drug
Abstract: These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4 × 200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.
Published: 2014

16. Multifocal cutaneous phaeohyphomycosis caused by Paraconiothyrium cyclothyrioides in an immunocompromised patient

Author: Malaure, Célie, Hoang, Stella, Bagny, Kelly, Tauziède-Espariat, Arnault, Garcia-Hermoso, Dea, Kamus, Laure, Traversier, Nicolas, Miltgen, Guillaume, Garrigos, Thomas, Laboratoire de microbiologie et virologie [CHU La Réunion], Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service des maladies infectieuses [CHU La Réunion], Service de dermatologie [CHU La Réunion], GHU Paris Psychiatrie et Neurosciences, 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), Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de La Réunion (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IRD-Centre National de la Recherche Scientifique (CNRS), and Centre Régional en Antibiothérapie (CRATb)
Subjects: [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience
Published: 2023

17. Copy Number Variation of Mitochondrial DNA Genes in Pneumocystis jirovecii According to the Fungal Load in BAL Specimens

Author: Alexandre Alanio, Nicolas Guigue, Marion Benazra, Maud Gits-Muselli, Samia Hamane, María José Buitrago, Stéphane Bretagne, Aude Sturny-Leclère, Clara Valero, Instituto de Salud Carlos III [Madrid] (ISC), 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), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], This work was supported by research project PI14CIII/00045 from the Spanish Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III. CV is supported by research fellowships from the Fondo de Investigaciones Sanitarias of the Spanish Ministry of Economy and Competitiveness (FI12/00095)., Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Microbiology (medical), Mitochondrial DNA, Nuclear gene, [SDV]Life Sciences [q-bio], 030106 microbiology, DNA quantification, lcsh:QR1-502, DHPS, Mitochondrion, Biology, Microbiology, lcsh:Microbiology, PcP, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pneumocystis jirovecii, Copy-number variation, Gene, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Original Research, carriage, Genetics, copy number variation, Ribosomal RNA, biology.organism_classification, Molecular biology, 3. Good health, mitochondria, real-time PCR
Abstract: Pneumocystis jirovecii is an unculturable fungus and the causative agent of Pneumocystis pneumonia, a life-threatening opportunistic infection. Although molecular diagnosis is often based on the detection of mtLSU rRNA mitochondrial gene, the number of copies of mitochondrial genes had not been investigated. We developed and optimized six real-time PCR assays in order to determine the copy number of four mitochondrial genes (mtSSU rRNA, mtLSU rRNA, NAD1, and CYTB) in comparison to nuclear genome (DHPS and HSP70) and tested 84 bronchoalveolar fluids of patients at different stages of the infection. Unexpectedly, we found that copy number of mitochondrial genes varied from gene to gene with mtSSU rRNA gene being more represented (37 copies) than NAD1 (23 copies), mtLSU rRNA (15 copies) and CYTB (6 copies) genes compared to nuclear genome. Hierarchical clustering analysis (HCA) allowed us to define five major clusters, significantly associated with fungal load (p = 0.029), in which copy number of mitochondrial genes was significantly different among them. More importantly, copy number of mtLSU rRNA, NAD1, and CYTB but not mtSSU rRNA differed according to P. jirovecii physiological state with a decreased number of copies when the fungal load is low. This suggests the existence of a mixture of various subspecies of mtDNA that can harbor different amplification rates. Overall, we revealed here an unexpected variability of P. jirovecii mtDNA copy number that fluctuates according to P. jirovecii's physiological state, except for mtSSU that is the most stable and the most present mitochondrial gene. This work was supported by research project PI14CIII/00045 from the Spanish Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III. CV is supported by research fellowships from the Fondo de Investigaciones Sanitarias of the Spanish Ministry of Economy and Competitiveness (FI12/00095). Sí
Published: 2016
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18. Early diagnosis and monitoring of mucormycosis by detection of circulating DNA in serum: retrospective analysis of 44 cases collected through the French Surveillance Network of Invasive Fungal Infections (RESSIF)

Author: L. Millon, R. Herbrecht, F. Grenouillet, F. Morio, A. Alanio, V. Letscher-Bru, S. Cassaing, T. Chouaki, C. Kauffmann-Lacroix, P. Poirier, D. Toubas, O. Augereau, S. Rocchi, D. Garcia-Hermoso, S. Bretagne, H. Dupont, J.P. Marolleau, A. Totet, C. Damiani, A. Berceanu, F. Larosa, J. Bonhomme, C. Chabrot, B. Bouteille, D. Boutoille, T. Gastinne, P. Peterlin, M. Gari Toussaint, D. Poisson, D. Briet, J. Buret, M. Legrand, B. Denis, E. Raffoux, A. Bergeron, A. Veinstein, C. Godet, Y. N'guyen, S. Diallo, M. Sabou, J. Denis, M.P. Ledoux, C. Recher, J. Ruiz, G. Desoubeaux, E. Bailly, E. Chachaty, F. Dromer, O. Lortholary, K. Sitbon, D. Hoinard, 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), Service d’Oncologie et d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, IICiMed - EA 1155, Université de Nantes (UN)-UFR Sciences et Techniques [Université de Nantes], Université de Nantes (UN)-UFR des Sciences Pharmaceutiques [Université de Nantes], Université de Nantes (UN), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris], Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Saint Louis [APHP], Université Paris Diderot - Paris 7 (UPD7), Les Hôpitaux Universitaires de Strasbourg (HUS), Service de Parasitologie-Mycologie [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Picardie Jules Verne (UPJV), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Centre National de la Recherche Scientifique (CNRS)-Université d'Auvergne - Clermont-Ferrand I (UdA), Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional d'Orléans (CHR), Immunologie cellulaire et moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de parasitologie et de mycologie médicales, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Istituto di Fisica dello Spazio Interplanetario (INAF), Consiglio Nazionale delle Ricerche [Roma] (CNR), Service d'hématologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hématologie Clinique [CHU Hôtel-Dieu, Nantes], Hôtel-Dieu de Nantes, Service d'Hématologie Clinique [Nantes] (Unité d'Investigation Clinique), Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Association de dépistage des cancers, Mutualité française, Pathologie et virologie moléculaire (PVM), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de pneumologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de physique des interfaces et des couches minces [Palaiseau] (LPICM), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Centre d'Etudes et d'Expertise sur les Risques, l'Environnement, la Mobilité et l'Aménagement - Direction Méditerranée (Cerema Direction Méditerranée), Centre d'Etudes et d'Expertise sur les Risques, l'Environnement, la Mobilité et l'Aménagement (Cerema), UMR1037, Cancer Research Center of Toulouse, Université de Tours, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), service de parasito-mycologie CHU Besancon, service de parasitologie mycologie CHU Jean Minjoz BESANCON, Hôpital Jean Minjoz-Hôpital Jean Minjoz, Université de Nantes ( UN ) - UFR Sciences et Techniques-UFR des Sciences Pharmaceutiques, Centre hospitalier universitaire de Nantes ( CHU Nantes ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Université Paris Diderot - Paris 7 ( UPD7 ), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ), Institut de Parasitologie et de Pathologie Tropicale, Université Paul Sabatier - Toulouse 3 ( UPS ) -CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], Université de Picardie Jules Verne ( UPJV ), CHU Amiens-Picardie, CHU de Poitiers, CHU Gabriel Montpied ( CHU ), CHU Clermont-Ferrand, Matrice extracellulaire et dynamique cellulaire - UMR 7369 ( MEDyC ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Reims Champagne-Ardenne ( URCA ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ), Centre Hospitalier Universitaire de Reims ( CHU de Reims ), Centre Hospitalier Régional d'Orléans ( CHR ), This work was supported by a grant from French Ministry of Health (Projet Hospitalier de Recherche Clinique, national-ModiMucor 2014-A00580-47). LM has received support for travel to meetings from Pfizer, MSD and Gilead. RH received honorariafrom Astellas, Basilea, Gilead, MSD, Pfizer and Schering-Plough and a research grant from Pfizer. SB received project funding from Renishaw Diagnostics, was sponsored by Pfizer and MSD to attend international meetings, and provided consultancy for Gilead., French Mycosis Study Group, 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), Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Cibles et Médicaments des Infections et de l'Immunité (IICiMed), Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), 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), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), CHU Gabriel Montpied [Clermont-Ferrand], Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Régional d'Orléans (CHRO), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Cibles et médicaments de l'infection, de l'immunité et du cancer (IICiMed), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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], Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and CHU Gabriel Montpied (CHU)
Subjects: 0301 basic medicine, Male, Pathology, [SDV]Life Sciences [q-bio], Comorbidity, Quantitative PCR, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Diagnosis, Sampling (medicine), 030212 general & internal medicine, DNA, Fungal, Fungemia, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, 80 and over, biology, General Medicine, Middle Aged, 3. Good health, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Real-time polymerase chain reaction, Population Surveillance, Mucorales, Female, France, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, Internal medicine, medicine, Humans, Mucormycosis, Survival rate, Survival analysis, Aged, Retrospective Studies, [ SDV ] Life Sciences [q-bio], Retrospective cohort study, medicine.disease, biology.organism_classification, Survival Analysis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, monitoring, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; The main objective of this study was to assess the diagnostic performance of a set of three Mucorales quantitative PCR assays in a retrospective multicentre study. Mucormycosis cases were recorded thanks to the French prospective surveillance programme (RESSIF network). The day of sampling of the first histological or mycological positive specimen was defined as day 0 (D0). Detection of circulating DNA was performed on frozen serum samples collected from D-30 to D30, using quantitative PCR assays targeting Rhizomucor, Lichtheimia, Mucor/Rhizopus. Forty-four patients diagnosed with probable (n = 19) or proven (n = 25) mucormycosis were included. Thirty-six of the 44 patients (81%) had at least one PCR-positive serum. The first PCR-positive sample was observed 9 days (range 0-28 days) before diagnosis was made using mycological criteria and at least 2 days (range 0-24 days) before imaging. The identifications provided with the quantitative PCR assays were all concordant with culture and/or PCR-based identification of the causal species. Survival rate at D84 was significantly higher for patients with an initially positive PCR that became negative after treatment initiation than for patients whose PCR remained positive (48% and 4%, respectively; p \textless10(-6)). The median time for complete negativity of PCR was 7 days (range 3-19 days) after initiation of l-AmB treatment. Despite some limitations due to the retrospective design of the study, we showed that Mucorales quantitative PCR could not only confirm the mucormycosis diagnosis when other mycological arguments were present but could also anticipate this diagnosis. Quantification of DNA loads may also be a useful adjunct to treatment monitoring.
Published: 2016

19. ECIL guidelines for preventing Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients

Author: Maertens, Johan, Cesaro, Simone, Maschmeyer, Georg, Einsele, Hermann, Donnelly, J. Peter, Alanio, Alexandre, Hauser, Philippe M., Lagrou, Katrien, Melchers, Willem J. G., Helweg-Larsen, Jannik, Matos, Olga, Bretagne, Stã©phane, Cordonnier, Catherine, Agrawal, Samir, Kibbler, Christopher, Pagliuca, SIMONE ANTONIO, Ward, Katherine, Akova, Murat, Herbrecht, Raoul, Mallet, Vincent, Ribaud, Patricia, Aljurf, Mahmoud, Averbuch, Dina, Engelhard, Dan, Berg, Thomas, Cornely, Oliver, Penack, Olaf, van Boemmel, Florian, von Lilienfeld-Toal, Marie, Blennow, Ola, Ljungman, Per, Bruggemann, Roger, Donnelly, Peter, Kullberg, Bart-Jan, Melchers, Willem, Calandra, Thierry, Hirsch, Hans, Marchetti, Oscar, Orasch, Christina, Tissot, Frederic, Castagnola, Elio, Girmenia, Corrado, Mikulska, Malgorzata, Pagano, Livio, Viscoli, Claudio, De La Camara, Rafael, Duarte, Rafael, Munoz, Patricia, Drgona, Lubos, Hargreaves, Ruth, Hubacek, Petr, Kouba, Michal, Racil, Zdenek, Klyasova, Galina, Pettrikos, George, Roilides, Emmanuel, Skiada, Anna, Rizzi-Puechal, Valã©rie, Sinko, Janos, Slavin, Monica, Styczynski, Jan, Tweddle, Lorraine, Wood, Craig, Department of Hematology, University Hospital Gasthuisberg, G.B. Rossi Hospital, Verona University, Medizinische Klinik, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Radboud university [Nijmegen], 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), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Lausanne University Hospital, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Rigshospitalet [Copenhagen], Copenhagen University Hospital, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), The ECIL-5 meeting was supported by unrestricted educational grants from Astellas Pharma, Gilead Sciences, Merck, and Pfizer., University Hospital Gasthuisberg [Leuven], Università degli studi di Verona = University of Verona (UNIVR), Radboud University [Nijmegen], Julius-Maximilians-Universität Würzburg (JMU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Microbiology (medical), Antifungal Agents, [SDV]Life Sciences [q-bio], 030106 microbiology, Pneumocitis jirovecii, Chemoprevention, Trimethoprim, Immunocompromised Host, 03 medical and health sciences, 0302 clinical medicine, Trimethoprim, Sulfamethoxazole Drug Combination, Humans, Pharmacology (medical), Pharmacology, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Sulfamethoxazole Drug Combination, Pneumocystis, Hematologic Neoplasms, Pneumonia, Pneumocystis, Stem Cell Transplantation, Transplant Recipients, Infectious Diseases, immunocomrpomised host, pneumonia, Pneumocitis jirovecii, Pneumonia, 3. Good health, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 030220 oncology & carcinogenesis, immunocomrpomised host, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Contains fulltext : 172373.pdf (Publisher’s version ) (Closed access) The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2-3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults ( A-II: ) and children ( A-I: ) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen ( B-II: ). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.
Published: 2016

20. [Sinonasal fungal infections are not exclusively due to mucorales and Aspergillus!]

Author: Arnault, Tauziède-Espariat, Michel, Wassef, Homa, Adle-Biassette, Alexandre, Alanio, Stéphane, Bretagne, Fanny, Lanternier, Mohammed, Boui, Olivier, Bouchaud, Pierre, Vironneau, Romain, Kania, Grégory, Jouvion, Fabrice, Chrétien, Marion, Classe, Service d'anatomie et cytologie pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], 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), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Hôpital Mohamed V, Rabat, Maroc, Service des maladies infectieuses et tropicales, Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Service d'oto-rhino-laryngologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), PRES Sorbonne Paris Cité, Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Neuropathologie, Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Parasitologie-Mycologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne-Université Paris 13 ( UP13 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Institut Pasteur [Paris] (IP), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Avicenne-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris 13 (UP13), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière
Subjects: Adult, Antifungal Agents, Invasive, [SDV]Life Sciences [q-bio], Mastoiditis, Alternariosis, Diagnosis, Differential, Fatal Outcome, Postoperative Complications, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, Humans, Aspergillosis, Mucormycosis, Sinusitis, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Retrospective Studies, Rhinitis, [ SDV ] Life Sciences [q-bio], Alternaria, Combined Modality Therapy, Shock, Septic, Phaeohyphomycosis, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Early Diagnosis, Debridement, Liposomes, Mucormycose, Female, Aspergillose
Abstract: International audience; Rhino-sinusal infections are serious diseases and possibly lethal. When they are invasive, we easily discuss apergilloses and mucormycoses. The confirmation of the diagnosis of mucormycosis need an extensive surgery for precise histopathological and mycological evaluation. The pathologist may be faced to other rare mycoses such as phaeohyphomycoses, which present different morphological features than mucormycoses and Aspergillus. Once the diagnosis is established, an appropriate antifungal treatment is quickly started. The aim of our work is to report two observations of phaeohyphomycoses, to describe their histopathological features, to discuss complementary diagnostic methods and to present the main differential diagnoses.
Published: 2016

21. New therapeutic strategies for invasive aspergillosis in the era of azole resistance: how should the prevalence of azole resistance be defined?

Author: Alanio, Alexandre, Denis, Blandine, Hamane, Samia, Raffoux, Emmanuel, Peffault de la Tour, Régis, Touratier, Sophie, Bergeron, Anne, Bretagne, Stéphane, Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), Mycologie moléculaire, Université Paris Diderot - Paris 7 (UPD7), Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-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), Service d'hématologie biologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d'Hématologie Greffe, Hospital Saint Louis, Pharmacie, Hôpital Saint-Louis, Service de pneumologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Azoles, Invasive Pulmonary Aspergillosis, Antifungal Agents, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Drug Resistance, Fungal, Aspergillus fumigatus, Incidence, [SDV]Life Sciences [q-bio], Prevalence, Humans, Microbial Sensitivity Tests, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience; Given reports showing a high prevalence of azole resistance in Aspergillus fumigatus, alternatives to azole therapy are discussed when a threshold of 10% of azole-resistant environmental isolates is reached. This raises the issue of calculation of this threshold, either on the prevalence of azole-resistant isolates as a whole or on the prevalence of azole-resistant cases in populations at risk of invasive aspergillosis (IA). For isolate evaluation, there are high disparities in routine microbiological procedures for the isolation of A. fumigatus and azole resistance detection. There are also huge differences between the microbiological work-up for diagnosing IA. Some centres rely on galactomannan detection alone without actively trying to culture appropriate samples, which affects reliability of the figures on the prevalence of resistance and thus the threshold of resistance. Moreover, reports from the laboratory could mix up figures from completely different patient populations: frequent azole-resistant isolates from pneumology patients and rare azole-resistant isolates from haematology patients. Therefore, to sum isolates from different specimens and different wards can lead to erroneous calculations for the restricted populations at risk of developing IA. In conclusion, assessing the incidence of azole resistance in A. fumigatus should be based on harmonized consensual microbiological methods and reports should be restricted to IA episodes in identified populations at risk of IA when the issue is to define an operational threshold for modifying recommendations.
Published: 2016

22. Prospective Evaluation of Serum β-Glucan Testing in Patients With Probable or Proven Fungal Diseases

Author: Fanny Lanternier, Anne-Laure Roupie, Christophe d'Enfert, Bénédicte Neven, Felipe Suarez, Anne Scemla, Marie-Elisabeth Bougnoux, Aurélie Dupuis, Denis Caillot, Cécile Schrimpf, Etienne Paubelle, Pierre Frange, Frédéric Dalle, Cécile Angebault, Olivier Lortholary, Aurélie Agathine, Université Paris Descartes - Paris 5 (UPD5), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'infectiologie Necker-Pasteur [CHU Necker], Laboratoire de parasitologie mycologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Réseau CENTAURE, Service Néphrologie et transplantation rénale Adultes [CHU Necker], Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Clinique (CHU de Dijon), Biologie et Pathogénicité fongiques, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris], This work was supported by the Association pour la Promotion de l′Enseignement et de la Recherche en Mycologie., Université Paris Descartes - Paris 5 ( UPD5 ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Biologie et Pathogénicité fongiques (BPF), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP), and Bougnoux, Marie-Elisabeth
Subjects: 0301 basic medicine, Antifungal, medicine.medical_specialty, Systemic mycosis, medicine.drug_class, 030106 microbiology, invasive fungal diseases, Aspergillosis, Gastroenterology, Prospective evaluation, Major Articles, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, In patient, 030212 general & internal medicine, Candida albicans, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, (1-3)-beta-D-glucan, diagnostic tool, kinetics, biology, (1-3)-β-d-glucan, business.industry, Odds ratio, Invasive candidiasis, medicine.disease, biology.organism_classification, 3. Good health, Infectious Diseases, Oncology, Immunology, business
Abstract: We evaluated the positivity of (1-3)-β-D-glucan, a serum marker of invasive fungal diseases (IFD), at diagnosis and during treatment. (1-3)-β-D-Glucan may not be an early marker but could prove useful for diagnosis of chronic IFD., Background. Early diagnosis and treatment are crucial in invasive fungal diseases (IFD). Serum (1-3)-β-d-glucan (BG) is believed to be an early IFD marker, but its diagnostic performance has been ambiguous, with insufficient data regarding sensitivity at the time of IFD diagnosis (TOD) and according to outcome. Whether its clinical utility is equivalent for all types of IFD remains unknown. Methods. We included 143 patients with proven or probable IFD (49 invasive candidiasis, 45 invasive aspergillosis [IA], and 49 rare IFD) and analyzed serum BG (Fungitell) at TOD and during treatment. Results. (1-3)-β-d-glucan was undetectable at TOD in 36% and 48% of patients with candidemia and IA, respectively; there was no correlation between negative BG results at TOD and patients' characteristics, localization of infection, or prior antifungal use. Nevertheless, patients with candidemia due to Candida albicans were more likely to test positive for BG at TOD (odds ratio = 25.4, P = .01) than patients infected with other Candida species. In 70% of the patients with a follow-up, BG negativation occurred in >1 month for candidemia and >3 months for IA. A slower BG decrease in patients with candidemia was associated with deep-seated localizations (P = .04). Thirty-nine percent of patients with rare IFD had undetectable BG at TOD; nonetheless, all patients with chronic subcutaneous IFD tested positive at TOD. Conclusions. Undetectable serum BG does not rule out an early IFD, when the clinical suspicion is high. After IFD diagnostic, kinetics of serum BG are difficult to relate to clinical outcome.
Published: 2016

23. Treatment with adalimumab for severe immune reconstitution inflammatory syndrome in an HIV-infected patient presenting with cryptococcal meningitis

Author: Jean-Michel Molina, Alexandre Alanio, G. Gaube, A. Gueguen, C. Lascoux, N. De Castro, A.-M. Zagdanski, Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de radiologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
Subjects: 0301 basic medicine, Cyclopropanes, Cryptococcose méningée, Antifungal Agents, Delayed Diagnosis, [SDV]Life Sciences [q-bio], Human immunodeficiency virus (HIV), Anti-Inflammatory Agents, Meningitis, Cryptococcal, medicine.disease_cause, Ventriculoperitoneal Shunt, 0302 clinical medicine, Immune Reconstitution Inflammatory Syndrome, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Hiv infected, Antiretroviral Therapy, Highly Active, 030212 general & internal medicine, Cameroon, ComputingMilieux_MISCELLANEOUS, Combined Modality Therapy, 3. Good health, Stavudine, Infectious Diseases, Lamivudine, Alkynes, Drug Therapy, Combination, Female, Cryptococcal meningitis, medicine.drug, Adult, Anti-HIV Agents, SRI, 030106 microbiology, 03 medical and health sciences, Immune reconstitution inflammatory syndrome, Adalimumab, medicine, Humans, AIDS-Related Opportunistic Infections, business.industry, Tumor Necrosis Factor-alpha, VIH, HIV, IRIS, medicine.disease, Benzoxazines, Immunology, Prednisone, business
Abstract: International audience; no abstract
Published: 2016

24. Diversity of Pneumocystis jirovecii during Infection Revealed by Ultra-Deep Pyrosequencing

Author: Alexandre eAlanio, Maud eGits-Muselli, Severine eMercier-Delarue, Françoise eDromer, Stéphane eBretagne, 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), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), Laboratoire de Microbiologie, 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), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: 0301 basic medicine, Microbiology (medical), Mitochondrial DNA, [SDV]Life Sciences [q-bio], 030106 microbiology, lcsh:QR1-502, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Pneumocystis pneumonia, Microbiology, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, lcsh:Microbiology, 03 medical and health sciences, symbols.namesake, Genotype, ultra-deep pyrosequencing, medicine, Pneumocystis jirovecii, heteroplasmy, Original Research, Sanger sequencing, Ribosomal RNA, biology.organism_classification, medicine.disease, Virology, Heteroplasmy, recombination, 3. Good health, mixed infection, mitochondria, symbols, Pyrosequencing, Public Health
Abstract: International audience; Pneumocystis jirovecii is an uncultivable fungal pathogen responsible for Pneumocystis pneumonia (PCP) in immunocompromised patients, the physiopathology of which is only partially understood. The diversity of the Pneumocystis strains associated with acute infection has mainly been studied by Sanger sequencing techniques precluding any identification of rare genetic events (\textless 20% frequency). We used next-generation sequencing to detect minority variants causing infection, and analyzed the complexity of the genomes of infection-causing P. jirovecii. Ultra-deep pyrosequencing (UDPS) of PCR amplicons of two nuclear target region [internal transcribed spacer 2 (ITS2) and dihydrofolate reductase (DHFR)] and one mitochondrial DNA target region [the mitochondrial ribosomal RNA large subunit gene (mtLSU)] was performed on 31 samples from 25 patients. UDPS revealed that almost all patients (n = 23/25, 92%) were infected with mixtures of strains. An analysis of repeated samples from six patients showed that the proportion of each variant change significantly (by up to 30%) over time on treatment in three of these patients. A comparison of mitochondrial and nuclear UDPS data revealed heteroplasmy in P. jirovecii. The recognition site for the homing endonuclease I-SceI was recovered from the mtLSU gene, whereas its two conserved motifs of the enzyme were not. This suggests that heteroplasmy may result from recombination induced by unidentified homing endonucleases. This study sheds new light on the biology of P. jirovecii during infection. PCP results from infection not with a single microorganism, but with a complex mixture of different genotypes, the proportions of which change over time due to intricate selection and reinfection mechanisms that may differ between patients, treatments, and predisposing diseases.
Published: 2016

25. Ten-Year Experience of Cutaneous and/or Subcutaneous Infections Due to Coelomycetes in France

Author: Guégan, Sarah, Garcia-Hermoso, Dea, Sitbon, Karine, Ahmed, Sarah, Moguelet, Philippe, Dromer, Françoise, Lortholary, Olivier, Group, French Mycosis Study, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Saint-Antoine (UMRS893), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [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), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Mycologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], CBS-KNAW Fungal Biodiversity Centre, Institute of the Royal Netherlands Academy of Arts and Sciences, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), 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), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Anatomie et Cytologie Pathologiques, CHU Tenon [APHP], Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Guitard, Juliette, 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 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), Centraalbureau voor Schimmelcultures Fungal Biodiversity Centre (CBS-KNAW), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), Centre de référence des mastocytoses (CEREMAST), French Mycosis Study Group: N Ait-Ammar, J Dunand, B Levy, L Moulonguet, V Zarrouk, S Kubab, C Thépot, G Gendrey, M Beaubrun, A L Bienvenu, S Euvrard, N Desbois, J C Meniane, S Diallo, D Toubas, S Cassaing, J Guitard, C Chochillon, C Rioux, N Dupin, A Paugam, V Zeller, M E Bougnoux, C Charlier, A Fekkar, J Tourret, A Alanio, S Bretagne, S Gallien, E Raffoux, C Frances, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP]
Subjects: 0301 basic medicine, Posaconazole, Pathology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Coelomycetes, subcutaneous abscess, Eumycetoma, Major Articles, 03 medical and health sciences, Medicopsis romeroi, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Paraconiothyrium sp, Subcutaneous abscess, Abscess, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Voriconazole, Chromoblastomycosis, biology, [ SDV ] Life Sciences [q-bio], business.industry, 030108 mycology & parasitology, biology.organism_classification, medicine.disease, cutaneous phaeohyphomycosis, 3. Good health, coelomycetes, [SDV] Life Sciences [q-bio], Phaeohyphomycosis, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, Oncology, business, medicine.drug
Abstract: Background. Coelomycetes are rarely but increasingly reported in association with human infections involving mostly skin and subcutaneous tissues, both in immunocompetent and immunocompromised patients. Coelomycetes constitute a heterogeneous group of filamentous fungi with distinct morphological characteristics in culture, namely an ability to produce asexual spores within fruit bodies. Methods. We included all cases of proven primary cutaneous and/or subcutaneous infections due to coelomycetes received for identification at the French National Reference Center for Invasive Mycoses and Antifungals between 2005 and 2014. Eumycetoma, chromoblastomycosis, and disseminated infections were excluded. Results. Eighteen cases were analyzed. The median age was 60.5 years. In all cases, patients originated from tropical or subtropical areas. An underlying immunodepression was present in 89% of cases. Cutaneous and/or subcutaneous lesions, mainly nodules, abscesses, or infiltrated plaques, were observed in distal body areas. Isolates of different genera of coelomycetes were identified: Medicopsis (6), Paraconiothyrium (3), Gloniopsis (3), Diaporthe (3), Peyronellaea (2), Lasiodiplodia (1). Lesion treatment consisted of complete (10) or partial (2) surgical excision and/or the use of systemic antifungal therapy, namely voriconazole (5) and posaconazole (4). Literature review yielded 48 additional cases of cutaneous and/or subcutaneous infections due to coelomycetes. Conclusions. Infectious diseases physicians should suspect coelomycetes when observing cutaneous and/or subcutaneous infections in immunocompromised hosts from tropical areas; a sequence-based approach is crucial for strains identification but must be supported by consistent phenotypic features; surgical treatment should be favored for solitary, well limited lesions; new triazoles may be used in case of extensive lesions, especially in immunocompromised patients.
Published: 2016

26. ECIL guidelines for the diagnosis of Pneumocystis jirovecii pneumonia in patients with haematological malignancies and stem cell transplant recipients

Author: Alanio, Alexandre, Hauser, Philippe M., Lagrou, Katrien, Melchers, Willem J. G., Helweg Larsen, Jannik, Matos, Olga, Cesaro, Simone, Maschmeyer, Georg, Einsele, Hermann, Donnelly, J. Peter, Cordonnier, Catherine, Maertens, Johan, Bretagne, Stã©phane, Agrawal, Samir, Kibbler, Christopher, Pagliuca, Antonio, Ward, Katherine, Akova, Murat, Herbrecht, Raoul, Mallet, Vincent, Ribaud, Patricia, Aljurf, Mahmoud, Averbuch, Dina, Engelhard, Dan, Berg, Thomas, Cornely, Oliver, Penack, Olaf, van Boemmel, Florian, von Lilienfeld Toal, Marie, Blennow, Ola, Ljungman, Per, Bruggemann, Roger, Donnelly, Peter, Kullberg, Bart Jan, Melchers, Willem, Calandra, Thierry, Hirsch, Hans, Marchetti, Oscar, Orasch, Christina, Tissot, Frederic, Castagnola, Elio, Girmenia, Corrado, Mikulska, MALGORZATA KAROLINA, Pagano, Livio, Viscoli, Claudio, De La Camara, Rafael, Duarte, Rafael, Munoz, Patricia, Drgona, Lubos, Hargreaves, Ruth, Hubacek, Petr, Kouba, Michal, Racil, Zdenek, Klyasova, Galina, Pettrikos, George, Roilides, Emmanuel, Skiada, Anna, Rizzi Puechal, Valã©rie, Sinko, Janos, Slavin, Monica, Styczynski, Jan, Tweddle, Lorraine, Wood, Craig, Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), Mycologie moléculaire, Université de Lausanne = University of Lausanne (UNIL), Université Catholique de Louvain = Catholic University of Louvain (UCL), Radboud University [Nijmegen], Rigshospitalet [Copenhagen], Copenhagen University Hospital, Universidade Nova de Lisboa = NOVA University Lisbon (NOVA), Università degli studi di Verona = University of Verona (UNIVR), Medizinische Klinik, Hämatologie und Onkologie, Klinikum Ernst von Bergmann, Julius Maximilians University Wurzburg, Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Hematology, University Hospital Gasthuisberg [Leuven], The ECIL-5 meeting was supported by unrestricted educational grants from Astellas Pharma, Gilead Sciences, Merck, and Pfizer, Université de Lausanne (UNIL), Radboud university [Nijmegen], G.B. Rossi Hospital, Verona University, University Hospital Gasthuisberg, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Julius-Maximilians-Universität Würzburg (JMU)
Subjects: 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Dapsone, Pneumocystis carinii, 03 medical and health sciences, Immunocompromised Host, 0302 clinical medicine, Diagnostic Tests, Internal medicine, medicine, Pneumocistis jirovecii, Humans, Routine, Pharmacology (medical), 030212 general & internal medicine, Intensive care medicine, Pharmacology, Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], business.industry, Diagnostic Tests, Routine, Pneumocystis, Pneumonia, Pneumocystis, Pneumonia, medicine.disease, Trimethoprim, Transplant Recipients, 3. Good health, Fludarabine, Regimen, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Hematologic Neoplasms, Alemtuzumab, Rituximab, business, Inflammatory diseases Radboud Institute for Molecular Life Sciences [Radboudumc 5], [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Pentamidine, medicine.drug, immunocompromised host, pneumonia, Pneumocistis jirovecii, Stem Cell Transplantation
Abstract: Item does not contain fulltext The Fifth European Conference on Infections in Leukaemia (ECIL-5) convened a meeting to establish evidence-based recommendations for using tests to diagnose Pneumocystis jirovecii pneumonia (PCP) in adult patients with haematological malignancies. Immunofluorescence assays are recommended as the most sensitive microscopic method (recommendation A-II: ). Real-time PCR is recommended for the routine diagnosis of PCP ( A-II: ). Bronchoalveolar lavage (BAL) fluid is recommended as the best specimen as it yields good negative predictive value ( A-II: ). Non-invasive specimens can be suitable alternatives ( B-II: ), acknowledging that PCP cannot be ruled out in case of a negative PCR result ( A-II: ). Detecting beta-d-glucan in serum can contribute to the diagnosis but not the follow-up of PCP ( A-II: ). A negative serum beta-d-glucan result can exclude PCP in a patient at risk ( A-II: ), whereas a positive test result may indicate other fungal infections. Genotyping using multilocus sequence markers can be used to investigate suspected outbreaks ( A-II: ). The routine detection of dihydropteroate synthase mutations in cases of treatment failure is not recommended ( B-II: ) since these mutations do not affect response to high-dose co-trimoxazole. The clinical utility of these diagnostic tests for the early management of PCP should be further assessed in prospective, randomized interventional studies.
Published: 2016

27. Nouvelles strategies pour le diagnostic microbiologique des mycoses viscerales

Author: Alexandre, Alanio, Stéphane, Bretagne, 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), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: Antigens, Fungal, Antifungal Agents, Spectrometry, [SDV]Life Sciences [q-bio], Candidiasis, Mass, Severity of Illness Index, Sensitivity and Specificity, Fungal, Mycoses, Molecular Diagnostic Techniques, Predictive Value of Tests, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Humans, Matrix-Assisted Laser Desorption-Ionization, Antigens, Biomarkers, Latex Fixation Tests, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology
Abstract: International audience; The recent improvements of the diagnosis of invasive mycoses have included the shortening of the species identification time for a rapid adaptation of the antifungal treatment, and the anticipation of the diagnosis thanks to biomarkers. Species identification is now achieved using MALDI-TOF 24 hours earlier than with the previous phenotypic tests. The aim is now to identify directly on positive blood bottle either using MALDI-TOF or molecular methods. The biomarkers are dominated by antigens (mannan, galactomanan, glucan) with available commercial kits. These antigens are mainly used as screening tests in patients at risk of invasive mycoses. Their main limitation is their weak specificity rather than their sensitivity. For circulating DNA, the quantitative real-time PCR format and the publication of recommendations for validation of diagnostic assays suggest they should be implemented soon in a diagnostic strategy.
Published: 2015

28. [Cryptococcus where they are not expected: Five case reports of extra-cerebral and extra-pulmonary cryptococcosis]

Author: Cazorla, Arnault, Alanio, Alexandre, Bretagne, Stéphane, Polivka, Marc, Shaar-Chneker, Caroline, Kaci, Rachid, Brouland, Jean-Philippe, Chretien, Fabrice, Jouvion, Grégory, Service de pathologie, Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Mycologie moléculaire, Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Laboratoire de Neuropathologie, Centre Hospitalier Sainte Anne, Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), AP-HP Hôpital Lariboisière [Paris], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Parasitologie-Mycologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Descartes - Paris 5 ( UPD5 ), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Adult, Male, Sacrum, Discitis, Cryptococcal, Biopsy, [SDV]Life Sciences [q-bio], Liver Abscess, Extrapulmonaire, Meningitis, Cryptococcal, Hepatitis B, Chronic, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, Dermatomycoses, Humans, Meningitis, Chronic, Extracérébral, Lymphatic Diseases, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Retrospective Studies, [ SDV ] Life Sciences [q-bio], AIDS-Related Opportunistic Infections, Immunohistochimie, Cryptococcosis, Hepatitis B, Immunohistochemistry, Extra-cerebral, Cryptococcus, Organ Specificity, Extra-pulmonary, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Cryptococcosis is a serious infection, possibly lethal, of worldwide distribution. It mainly affects immunosuppressed patients resulting with pulmonary and/or meningeal involvements or disseminated infections. Due to the rarity of visceral and osseous infections, and to the absence of specific clinical symptoms, this diagnosis is often deferred. Resulting of diagnostic errors, samples are often directed to the department of pathology and more rarely to the department of mycology. Histopathological examination appears crucial, highlighting encapsulated yeasts with alcian blue staining. Once the diagnosis is performed, an appropriate antifungal therapy must be quickly introduced because these infections are associated with a high mortality rate. The aim of our work was to report five extra-cerebral and extra-pulmonary cryptococcosis cases, to describe their histopathological features, to evoke diagnostic techniques and to discuss the differential diagnoses.
Published: 2015

29. Epidemiological trends in invasive aspergillosis in France: the SAIF network (2005–2007)

Author: Stéphane Bretagne, B. Lebeau, F. de Monbrison, Olivier Lortholary, Karine Sitbon, Françoise Dromer, Jean-Pierre Gangneux, Bruno Coignard, Y. Le Strat, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Signalisation et Réponses aux Agents Infectieux et Chimiques (SeRAIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Parasitologie-Mycologie [Rennes], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Laboratoire de parasitologie-mycologie, CHU Grenoble, Laboratoire de Parasitologie-Mycologie, Centre Hospitalo-Universitaire de Lyon, Département des maladies infectieuses, Institut de Veille Sanitaire (INVS), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Biologie moléculaire et immunologie parasitaires et fongiques (BIPAR), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Veille Sanitaire, Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Université de Rennes (UR), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Laboratoire de santé animale, sites de Maisons-Alfort et de Normandie, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Signalisation et Réponses aux Agents Infectieux et Chimiques ( SeRAIC ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140, Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Biologie moléculaire et immunologie parasitaires et fongiques ( BIPAR ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -AFSSA-Ecole Nationale Vétérinaire d'Alfort-Institut National de la Recherche Agronomique ( INRA ), CHU Necker - Enfants Malades [AP-HP], Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140, and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, Epidemiology, MESH : Prospective Studies, MESH : Aged, Aspergillosis, Mannans, 0302 clinical medicine, MESH: Immunocompromised Host, Prospective Studies, MESH: Incidence, Aged, 80 and over, Invasive Pulmonary Aspergillosis, 0303 health sciences, MESH: Middle Aged, Incidence, General Medicine, MESH : Incidence, 3. Good health, Aspergillus, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Young Adult, Drug Therapy, Combination, Microbiology (medical), MESH: Invasive Pulmonary Aspergillosis, medicine.medical_specialty, MESH : Young Adult, 03 medical and health sciences, Galactomannan, Pharmacotherapy, MESH: Mannans, MESH : Adolescent, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, Aged, MESH: Adolescent, MESH: Humans, MESH : Seasons, 030306 microbiology, MESH : Humans, MESH: Adult, MESH: Antifungal Agents, medicine.disease, chemistry, galactomannan, Immunology, MESH: Female, Antifungal Agents, chemistry.chemical_compound, MESH: Aged, 80 and over, Risk Factors, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Risk Factors, MESH : Female, 030212 general & internal medicine, Prospective cohort study, MESH: Aged, Incidence (epidemiology), MESH : Aspergillus, MESH : Immunocompromised Host, Middle Aged, MESH : Adult, MESH: Hospitals, MESH : Risk Factors, Hospitals, MESH : Hospitals, Infectious Diseases, MESH: Aspergillus, outcome, Female, France, Seasons, medicine.drug, Adult, Adolescent, MESH : Male, MESH : Antifungal Agents, Immunocompromised Host, Young Adult, Internal medicine, voriconazole, medicine, MESH : France, Voriconazole, invasive aspergillosis, business.industry, MESH : Drug Therapy, Combination, Galactose, MESH: Male, MESH: Prospective Studies, MESH: France, Transplantation, MESH: Drug Therapy, Combination, MESH : Invasive Pulmonary Aspergillosis, Caspofungin, business, MESH : Mannans, MESH: Seasons
Abstract: International audience; A prospective (2005-2007) hospital-based multicentre surveillance of EORTC/MSG-proven or probable invasive aspergillosis (IA) cases whatever the underlying diseases was implemented in 12 French academic hospitals. Admissions per hospital and transplantation procedures were obtained. Cox regression models were used to determine risk factors associated with the 12-week overall mortality. With 424 case-patients included, the median incidence/hospital was 0.271/10(3) admissions (range 0.072-0.910) without significant alteration of incidence and seasonality over time. Among the 393 adults (62% men, 56 years (16-84 years)), 15% had proven IA, 78% haematological conditions, and 92.9% had lung involvement. Acute leukaemia (34.6%) and allogeneic stem cell transplantation (21.4%) were major host factors, together with chronic lymphoproliferative disorders (21.6%), which emerged as a new high-risk group. The other risk host factors consisted of solid organ transplantation (8.7%), solid tumours (4.3%), systemic inflammatory diseases (4.6%) and chronic respiratory diseases (2.3%). Serum galactomannan tests were more often positive (≥69%) for acute leukaemia and allogeneic stem cell transplantation than for the others (
Published: 2011

30. Prior Caspofungin Exposure in Patients with Hematological Malignancies Is a Risk Factor for Subsequent Fungemia Due to Decreased Susceptibility in Candida spp.: a Case-Control Study in Paris, France

Author: Karine Boukris-Sitbon, Olivier Lortholary, Marie Desnos-Ollivier, Françoise Dromer, Didier Guillemot, Elodie Blanchard, Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), 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)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Thérapeutique Recombinante Expérimentale ( TIMC-IMAG-THEREX ), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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 Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-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)
Subjects: Male, Antifungal Agents, Multivariate analysis, MESH : Aged, Drug resistance, Echinocandins, chemistry.chemical_compound, 0302 clinical medicine, Caspofungin, Risk Factors, MESH: Risk Factors, polycyclic compounds, MESH : Female, Pharmacology (medical), 030212 general & internal medicine, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Fungemia, Candida, MESH: Aged, 0303 health sciences, MESH: Middle Aged, Middle Aged, MESH : Risk Factors, MESH: Case-Control Studies, 3. Good health, Infectious Diseases, Hematologic Neoplasms, Female, France, MESH : Hematologic Neoplasms, MESH : Case-Control Studies, medicine.medical_specialty, MESH : Male, MESH : Antifungal Agents, Clinical Therapeutics, Biology, MESH: Drug Resistance, Fungal, Lipopeptides, 03 medical and health sciences, Drug Resistance, Fungal, MESH: Fungemia, MESH: Candida, Internal medicine, medicine, Humans, MESH : Middle Aged, Risk factor, MESH : France, Aged, MESH : Echinocandins, Pharmacology, MESH: Humans, 030306 microbiology, MESH: Echinocandins, MESH : Humans, Case-control study, MESH : Drug Resistance, Fungal, Odds ratio, bacterial infections and mycoses, MESH: Antifungal Agents, medicine.disease, MESH: Male, Confidence interval, MESH: France, MESH : Fungemia, chemistry, Case-Control Studies, Immunology, MESH: Female, MESH : Candida, MESH: Hematologic Neoplasms
Abstract: Infections due to caspofungin-resistant Candida isolates in patients exposed to caspofungin therapy are increasing. We report here a nested case-control study which aimed at identifying factors associated with bloodstream infections caused by Candida spp. having reduced susceptibility to caspofungin (CRSC) in adults suffering from hematological malignancies. In univariate and multivariate analyses, infections with CRSC were associated with caspofungin exposure in the previous 30 days (odds ratio [OR] = 5.25; 95% confidence interval [95% CI], 1.68–16.35) and with an age of ≤65 years (OR = 3.27; 95% CI, 1.26–8.50).
Published: 2011

31. The current state of clinical mycology in Africa: a European Confederation of Medical Mycology and International Society for Human and Animal Mycology survey

Author: Cândida Driemeyer, Diego R Falci, Rita O Oladele, Felix Bongomin, Bright K Ocansey, Nelesh P Govender, Martin Hoenigl, Jean Pierre Gangneux, Cornelia Lass-Flörl, Oliver A Cornely, Alexandre Alanio, Jesus Guinea, C Orla Morrissey, Riina Rautemaa-Richardson, Arunaloke Chakrabarti, Jacques F Meis, Caroline Bruns, Jannik Stemler, Alessandro C Pasqualotto, Federal University of Health Sciences of Porto Alegre = Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Hospital de Clínicas de Porto Alegre (HCPA), University of Lagos, Gulu University, Partenaires INRAE, University of Manchester [Manchester], University of the Witwatersrand [Johannesburg] (WITS), University of California [San Diego] (UC San Diego), University of California (UC), Medical University of Graz, 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 Pontchaillou [Rennes], Leopold Franzens Universität Innsbruck - University of Innsbruck, German Center for Infection Research - Partner Site Bonn-Cologne (DZIF), Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Monash university, CSIR-Institute of Microbial Technology [Chandigarh] (IMTech), Council of Scientific and Industrial Research [India] (CSIR), and Radboud University Medical Center [Nijmegen]
Subjects: MESH: Fungi, Microbiology (medical), Antifungal Agents, MESH: Humans, [SDV]Life Sciences [q-bio], Fungi, Nigeria, Mycology, MESH: Antifungal Agents, Microbiology, Infectious Diseases, Mycoses, Virology, Animals, Humans, MESH: Animals, MESH: Nigeria
Abstract: International audience; Africa, although not unique in this context, is a favourable environment for fungal infections, given the high burden of risk factors. An online survey was developed asking about laboratory infrastructure and antifungal drug availability. We received 40 responses (24.4% response rate) of 164 researchers contacted from 21 African countries. Only five institutions (12.5%) of 40 located in Cameroon, Kenya, Nigeria, Sudan, and Uganda potentially fulfilled the minimum laboratory requirements for European Confederation of Medical Mycology Excellence Centre blue status. Difficulties included low access to susceptibility testing for both yeasts and moulds (available in only 30% of institutions) and Aspergillus spp antigen detection (available in only 47.5% of institutions as an in-house or outsourced test), as well as access to mould-active antifungal drugs such as amphotericin B deoxycholate (available for 52.5% of institutions), itraconazole (52.5%), voriconazole (35.0%), and posaconazole (5.0%). United and targeted efforts are crucial to face the growing challenges in clinical mycology.
Published: 2022

32. Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data

Author: Elie Azoulay, Sébastien Bailly, Jean-François Timsit, Olivier Lortholary, Olivier Leroy, Jean-Pierre Gangneux, Pierre-François Perrigault, Didier Guillemot, Philippe Montravers, Jean-Paul Mira, Jean-Michel Constantin, Hervé Dupont, Université Joseph Fourier - Grenoble 1 (UJF), 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), Hôpital Chatiliez, Service d'anesthésie - réanimation chirurgicale [CHU Bichat], Université Paris Diderot - Paris 7 (UPD7)-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 d'Anésthésie Réanimation [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Amiens-Picardie, Pharmacoépidémiologie et maladies infectieuses (PhEMI), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation polyvalente, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Parasitologie-Mycologie [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Bichat - Claude Bernard, 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)-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Département anesthésie et réanimation, CHU Clermont-Ferrand-Hôpital d'Estaing, Centre hospitalier universitaire d'Amiens (CHU Amiens-Picardie), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Joseph Fourier - Grenoble 1 ( UJF ), Infection, Antimicrobiens, Modélisation, Evolution ( IAME ), 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 ), Service d'anesthésie - réanimation chirurgicale, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Centre hospitalier universitaire d'Amiens ( CHU Amiens-Picardie ), Pharmacoépidémiologie et maladies infectieuses ( PhEMI ), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Male, medicine.medical_specialty, Antifungal Agents, Critical Illness, [SDV]Life Sciences [q-bio], Observation, Comorbidity, Critical Care and Intensive Care Medicine, Severity of Illness Index, Time-to-Treatment, law.invention, Echinocandins, law, Anesthesiology, Internal medicine, Severity of illness, Humans, Multicenter Studies as Topic, Medicine, Candidiasis, Invasive, Hospital Mortality, Prospective Studies, Prospective cohort study, Intensive care medicine, Fluconazole, Survival analysis, Aged, [ SDV ] Life Sciences [q-bio], business.industry, Middle Aged, medicine.disease, Survival Analysis, Intensive care unit, 3. Good health, Intensive Care Units, Logistic Models, Outcome and Process Assessment, Health Care, Disease Progression, Female, France, business, De-escalation, medicine.drug
Abstract: International audience; PURPOSE: Systemic antifungal therapy (SAT) of invasive candidiasis needs to be initiated immediately upon clinical suspicion. Controversies exist about adequate time and potential harm of antifungal de-escalation (DE) in documented and suspected candidiasis in ICU patients. Our objective was to investigate whether de-escalation within 5 days of antifungal initiation is associated with an increase of the 28-day mortality in SAT-treated non-neutropenic adult ICU patients. METHODS: From the 835 non-neutropenic adults recruited in the multicenter prospective observational AmarCAND2 study, we selected the patients receiving systemic antifungal therapy for a documented or suspected invasive candidiasis in the ICU and who were still alive 5 days after SAT initiation. They were included into two groups according to the occurrence of observed SAT de-escalation before day 6. The average causal SAT de-escalation effect on 28-day mortality was evaluated by using a double robust estimation. RESULTS: Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22 %), including 48 (34 %) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de-escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95 % CI 0.76-1.66). CONCLUSION: In non-neutropenic critically ill adult patients with documented or suspected invasive candidiasis, SAT de-escalation within 5 days was not related to increased day-28 mortality but it was associated with decreased SAT consumption. These results suggest for the first time that SAT de-escalation may be safe in these patients
Published: 2015

33. Prospective pilot study of high-dose (10 mg/kg/day) liposomal amphotericin B (L-AMB) for the initial treatment of mucormycosis

Author: Benoit Guery, Pierre BUFFET, Stéphane Bretagne, Frédéric GRENOUILLET, Benjamin Wyplosz, Tristan Ferry, André Paugam, Yvon STERKERS, Sophie Cassaing, Philippe Moreau, Anne-Lise Bienvenu, Raoul Herbrecht, Anne Thiebaut-Bertrand, Mathilde Hunault, Cedric Arvieux, Jean-Pierre Gangneux, Boualem Sendid, Olivia Freynet, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Radiologie et imagerie médicale [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut de génétique et microbiologie [Orsay] (IGM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Mycologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Service d’Oncologie et d’Hématologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, Space Science Institute [Boulder] (SSI), Service greffe de moelle osseuse, Université Paris Diderot - Paris 7 (UPD7)-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), Centre d'infectiologie Necker-Pasteur [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], This work was supported by a grant from Gilead Sciences, but the sponsor took no part in the scientific evaluation. L-AMB was kindly provided by Gilead Sciences., We thank Assistance Publique-Hôpitaux de Paris, promoter of the study. We thank URC Paris Descartes Necker (Beatrice Barbier) for the implementation, monitoring and data management of the study. We also thank Eric Dannaoui and Michel Huerre for their help in isolate collection and pathological slide reviews and Susan DeWolf for her helpful comments prior to submission. We thank Muriel Vray, Michel Tod, Vincent Jullien, Agnes Lefort and Caroline Charlier-Woerther for their participation in the safety committee., Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Unité de recherche clinique / Centre d'investigation clinique [CHU Necker], Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Hôpital de Hautepierre [Strasbourg], and AP-HP - Hôpital Bichat - Claude Bernard [Paris]
Subjects: Male, Antifungal Agents, [SDV]Life Sciences [q-bio], Pilot Projects, MESH: Mucormycosis/surgery, Gastroenterology, chemistry.chemical_compound, Amphotericin B, MESH: Child, Pharmacology (medical), Prospective Studies, Child, Prospective cohort study, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, MESH: Treatment Outcome, Response rate (survey), MESH: Aged, MESH: Middle Aged, Incidence (epidemiology), Middle Aged, MESH: Infant, 3. Good health, Treatment Outcome, Infectious Diseases, MESH: Young Adult, Child, Preschool, Female, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, Adolescent, MESH: Amphotericin B/administration & dosage, MESH: Mucormycosis/drug therapy, Young Adult, Internal medicine, medicine, Humans, Mucormycosis, MESH: Debridement, Aged, MESH: Antifungal Agents/administration & dosage, Pharmacology, MESH: Adolescent, Creatinine, MESH: Humans, business.industry, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, MESH: Pilot Projects, MESH: Male, MESH: Prospective Studies, Surgery, Clinical trial, Regimen, Debridement, chemistry, business, MESH: Female
Abstract: International audience; Background: Mucormycosis incidence is increasing and is associated with a high rate of mortality. Although lipid-based formulations of amphotericin B are the recommended first-line treatment, only one prospective trial in a limited number of patients has been performed to evaluate this regimen. Methods: Patients with proven or probable mucormycosis were included between June 2007 and March 2011. Patients were scheduled to receive 10 mg/kg/day liposomal amphotericin B (L-AMB) monotherapy for 1 month and surgery was performed when appropriate. The primary outcome was response rate at week 4 or at the end of treatment (EOT) if before week 4, evaluated by an independent committee. ClinicalTrials.gov Identifier: NCT00467883. Results: Forty patients were enrolled. Response was analysed in 33 patients at week 4. Most patients had a haem-atological malignancy as their primary underlying disease (53%). Seventy-one percent of patients underwent therapeutic surgery. The response rate at week 4 or at EOT was 36%, with 18% partial responses and 18% complete responses. The response rate at week 12 was 45%, with 13% partial responses and 32% complete responses. Overall mortality was 38% at week 12 and 53% at week 24. Serum creatinine doubled in 16 (40%) patients and returned to normal levels within 12 weeks in 10/16 (63%). Conclusions: High-dose LAMB for mucormycosis, in combination with surgery in 71% of cases, was associated with an overall response rate of 36% at week 4 and 45% at week 12 and creatinine level doubling in 40% of patients (transient in 63%). These results may serve as the basis for future clinical trials.
Published: 2015

34. High diversity of non-sporulating moulds in respiratory specimens of immunocompromised patients: should all the species be reported when diagnosing invasive aspergillosis?

Author: Martine Olivi, Odile Cabaret, Stéphane Bretagne, Catherine Cordonnier, Dea Garcia-Hermoso, Jean-Marc Costa, Françoise Foulet, Alexandre Alanio, Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), Université Paris Diderot - Paris 7 (UPD7), Mycologie moléculaire, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de parasitologie mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe hospitalier Albert Chenevier – Henri Mondor, Laboratoire CERBA, Laboratoire CERBA [Saint Ouen l'Aumône], Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Spores, Male, [SDV]Life Sciences [q-bio], Aspergillosis, Aspergillus fumigatus, Genus, Respiratory system, DNA, Fungal, Child, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Invasive Pulmonary Aspergillosis, 0303 health sciences, immunocompromised patient, biology, non-sporulating mould, General Medicine, Biodiversity, Spores, Fungal, Middle Aged, 3. Good health, Infectious Diseases, Phenotype, Fungal, Child, Preschool, Hematologic Neoplasms, Penicillium, Female, Sequence Analysis, Adult, Adolescent, Virulence, Dermatology, Microbiology, 03 medical and health sciences, Young Adult, Immunocompromised Host, medicine, Humans, In patient, Internal transcribed spacer, Preschool, Respiratory specimens, 030304 developmental biology, Aged, invasive aspergillosis, 030306 microbiology, Infant, Sequence Analysis, DNA, DNA, medicine.disease, biology.organism_classification, respiratory tract diseases, fungi
Abstract: International audience; Non-sporulating moulds (NSMs) isolated from respiratory specimens are usually discarded without further testing although they may have pathogenic effects in immunocompromised patients. The objective of this study was to determine the identity and frequency of NSMs in patients with haematological malignancies. We analysed the mycological results of 251 consecutive respiratory samples from 104 haematology patients. Yeast and sporulating moulds were identified at the genus/species level according to their phenotypic features. NSMs were identified by internal transcribed spacer (ITS) sequencing. We detected 179 positive samples, of which 10.1% (18/179) were mixtures of moulds and 26.3% (47/179) were mixtures of moulds and yeast. We identified 142 moulds belonging to 11 different genera/species or groups, with Aspergillus fumigatus (n = 50), Penicillium spp. (n = 31) and NSM (n = 24) being the most frequently isolated species. Twenty-two NSMs were successfully sequenced: 18 were basidiomycetes and six were ascomycetes, corresponding to 16 different genera/species. NSMs were isolated with A. fumigatus in the same sample or in a subsequent sample in five patients with probable invasive aspergillosis. The conclusion is that the respiratory specimens of immunocompromised patients frequently contain very diverse mould species that may increase the virulence of pathogenic species. Reporting all mould species isolated when diagnosing invasive fungal infection could test this hypothesis.
Published: 2015

35. Dual Invasive Infection with Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides in a Renal Transplant Recipient: Case Report and Comprehensive Review of the Literature of Phaeoacremonium Phaeohyphomycosis

Author: Dea Garcia-Hermoso, Sébastien Gallien, Stéphane Bretagne, Alexandre Alanio, Bénédicte Levy, Marie-Noëlle Peraldi, Giovanna Melica, Denis Glotz, Marie-Alice Colombier, B. Denis, Service de maladies infectieuses et tropicales [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), 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) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Service de Néphrologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 (UPD7)-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), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], 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)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: Microbiology (medical), Male, medicine.medical_specialty, Antifungal Agents, [SDV]Life Sciences [q-bio], Mycology, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Chronic granulomatous disease, Fatal Outcome, Ascomycota, Amphotericin B, medicine, Phaeoacremonium, Humans, 030212 general & internal medicine, Kidney transplantation, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, Voriconazole, 0303 health sciences, 030306 microbiology, business.industry, Coinfection, medicine.disease, Dermatology, Kidney Transplantation, Transplant Recipients, 3. Good health, Surgery, Phaeohyphomycosis, Debridement, Mycoses, Drainage, business, medicine.drug
Abstract: Despite increasing reports of human infection, data about the optimal care of Phaeoacremonium infections are missing. We report a case of an infection due to Phaeoacremonium parasiticum and Paraconiothyrium cyclothyrioides , initially localized to skin and soft tissue, in a kidney transplant patient. Despite surgical drainage and excision of the lesion and combination antifungal therapy with voriconazole and liposomal amphotericin B, a disseminated infection involving the lungs and brain developed and led to death. We performed a systematic literature review to assess the general features and outcome of human infections due to Phaeoacremonium species. Thirty-six articles were selected, and 42 patients, including ours, were reviewed. Thirty-one patients (74%) were immunocompromised because of organ or bone marrow transplantation ( n = 17), diabetes or glucose intolerance ( n = 10), rheumatoid arthritis or Still's disease ( n = 4), chronic hematological diseases ( n = 3), or chronic granulomatous disease ( n = 3). Ten patients (24%) reported initial cutaneous trauma. Skin and soft tissue infections represented 57% of infections ( n = 24), and disseminated infections, all occurring in immunocompromised patients, represented 14% of infections ( n = 6). The main antifungal drugs used were azoles ( n = 41) and amphotericin B ( n = 16). Surgical excision or drainage was performed in 64% of cases ( n = 27). The cure rate was 67% ( n = 28). There were 10% cases of treatment failure or partial response ( n = 4), 19% relapses ( n = 8), and 7% losses to follow-up ( n = 3). The death rate was 19% ( n = 8). Management of Phaeoacremonium infections is complex because of slow laboratory identification and limited clinical data, and treatment relies on a combination of surgery and systemic antifungal therapy.
Published: 2015

36. Cryptococcosis Serotypes Impact Outcome and Provide Evidence of Cryptococcus neoformans Speciation

Author: Stéphane Bretagne, Luc De Saint-Martin, André Paugam, Bernard Bouteille, Pierre Lozeron, Laurence Baril, Sophie Cassaing, Cedric Arvieux, Jean-Pierre Gangneux, Sweta M. Patel, Philippe Poirier, Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Department of Molecular Genetics and Microbiology, Duke University Medical Center, The financial contribution of Institut Pasteur (through the 'programmede recherche clinique'), Institut de Veille Sanitaire (through theNational Reference Center for Invasive Mycoses and Antifungals) and ofEnsemble contre le Sida-SIDACTION (through a grant to Françoise Dromer)is gratefully acknowledged. The funders had no role in study design,data collection and analysis, decision to publish, or preparation of themanuscript., The French Cryptococcosis Study Group, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris] (IP)
Subjects: Serotype, Antifungal Agents, Genotype, Population, Flucytosine, Biology, Serogroup, Microbiology, Virology, medicine, Humans, education, Cerebrospinal Fluid, Cryptococcus neoformans, education.field_of_study, Coinfection, Meningoencephalitis, Cryptococcosis, medicine.disease, biology.organism_classification, QR1-502, 3. Good health, Treatment Outcome, Multilocus sequence typing, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, medicine.drug, Research Article
Abstract: Cryptococcus neoformans is a human opportunistic fungal pathogen causing severe disseminated meningoencephalitis, mostly in patients with cellular immune defects. This species is divided into three serotypes: A, D, and the AD hybrid. Our objectives were to compare population structures of serotype A and D clinical isolates and to assess whether infections with AD hybrids differ from infections with the other serotypes. For this purpose, we analyzed 483 isolates and the corresponding clinical data from 234 patients enrolled during the CryptoA/D study or the nationwide survey on cryptococcosis in France. Isolates were characterized in terms of ploidy, serotype, mating type, and genotype, utilizing flow cytometry, serotype- and mating type-specific PCR amplifications, and multilocus sequence typing (MLST) methods. Our results suggest that C. neoformans serotypes A and D have different routes of multiplication (primarily clonal expansion versus recombination events for serotype A and serotype D, respectively) and important genomic differences. Cryptococcosis includes a high proportion of proven or probable infections (21.5%) due to a mixture of genotypes, serotypes, and/or ploidies. Multivariate analysis showed that parameters independently associated with failure to achieve cerebrospinal fluid (CSF) sterilization by week 2 were a high serum antigen titer, the lack of flucytosine during induction therapy, and the occurrence of mixed infection, while infections caused by AD hybrids were more likely to be associated with CSF sterilization. Our study provides additional evidence for the possible speciation of C. neoformans var. neoformans and grubii and highlights the importance of careful characterization of causative isolates., IMPORTANCE Cryptococcus neoformans is an environmental fungus causing severe disease, estimated to be responsible for 600,000 deaths per year worldwide. This species is divided into serotypes A and D and an AD hybrid, and these could be considered two different species and an interspecies hybrid. The objectives of our study were to compare population structures of serotype A and serotype D and to assess whether infections with AD hybrids differ from infections with serotype A or D isolates in terms of clinical presentation and outcome. For this purpose, we used clinical data and strains from patients diagnosed with cryptococcosis in France. Our results suggest that, according to the serotype, isolates have different routes of multiplication and high genomic differences, confirming the possible speciation of serotypes A and D. Furthermore, we observed a better prognosis for infections caused by AD hybrid than those caused by serotype A or D, at least for those diagnosed in France.
Published: 2015

37. Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry

Author: Benoit Guery, Pierre BUFFET, Stéphane Bretagne, Frédéric GRENOUILLET, Benjamin Wyplosz, Tristan Ferry, André Paugam, Sophie Cassaing, Florent Morio, Maud GITS-MUSELLI, Anne Thiebaut-Bertrand, Mathilde Hunault, Cedric Arvieux, Jean-Pierre Gangneux, Anne Bergeron, Stéphane Ranque, Boualem Sendid, Olivia Freynet, 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), Université Paris Diderot - Paris 7 (UPD7), Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Laboratoire de microbiologie, Hopital Saint-Louis [AP-HP] (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), Service de pneumologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service d’anesthésie-réanimation [AP-HP Hôpital Saint-Louis], AP-HP Hôpital Saint-Louis, Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Minatec, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Marqueurs cardiovasculaires en situation de stress (MASCOT (UMR_S_942 / U942)), Université Paris 13 (UP13)-Université Paris-Sud - Paris 11 (UP11)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], 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), Laboratoire de Parasitologie-Mycologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Université Paris Diderot - Paris 7 ( UPD7 ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire ( CNRMA ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Microbiological Techniques, Time Factors, [SDV]Life Sciences [q-bio], Culture, Polymerase Chain Reaction, law.invention, law, Pathology, Prospective Studies, Pathology, Molecular, DNA, Fungal, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Polymerase chain reaction, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, Electrospray Ionization, General Medicine, Infectious Diseases, Real-time polymerase chain reaction, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, PCR, Fungal, Mucorales identification, Mucorales, Sequence Analysis, Microbiology (medical), Spectrometry, Mass, Electrospray Ionization, Electrospray ionization, electrospray-ionization mass spectrometry, Mass spectrometry, Real-Time Polymerase Chain Reaction, Microbiology, medicine, Humans, Mucormycosis, Internal transcribed spacer, [ SDV ] Life Sciences [q-bio], Spectrometry, Molecular, Sequence Analysis, DNA, DNA, Ribosomal RNA, Mass, biology.organism_classification, medicine.disease, Molecular biology, species level
Abstract: International audience; Molecular methods are crucial for mucormycosis diagnosis because cultures are frequently negative, even if microscopy suggests the presence of hyphae in tissues. We assessed PCR/electrospray-ionization mass spectrometry (PCR/ESI-MS) for Mucorales identification in 19 unfixed tissue samples from 13 patients with proven or probable mucormycosis and compared the results with culture, quantitative real-time PCR, 16S-23S rRNA gene internal transcribed spacer region (ITS PCR) and 18S PCR sequencing. Concordance with culture identification to both genus and species levels was higher for PCR/ESI-MS than for the other techniques. Thus, PCR/ESI-MS is suitable for Mucorales identification, within 6 hours, for tissue samples for which microscopy results suggest the presence of hyphae.
Published: 2015

38. Correlation Between Pneumocystis jirovecii Mitochondrial Genotypes and High and Low Fungal Loads Assessed by Single Nucleotide Primer Extension Assay and Quantitative Real-Time PCR

Author: Stéphane Bretagne, Ana Berceanu, Jean-Marc Costa, Alexandre Alanio, Anne-Pauline Bellanger, Odile Cabaret, Laurence Millon, Françoise Foulet, Catherine Cordonnier, Martine Olivi, 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), Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire CERBA, Laboratoire CERBA [Saint Ouen l'Aumône], Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Parasitologie Mycologie, Hôpitaux Universitaires Henri-Mondor, 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), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), Laboratoire de Parasitologie-Mycologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Institut de Recherches sur les lois Fondamentales de l'Univers ( IRFU ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Geography, MESH : Echinococcus multilocularis, Pneumocystis carinii, Primer extension, MESH: Risk Factors, Genotype, MESH: Animals, MESH: Residence Characteristics, MESH: Incidence, MESH: Disease Outbreaks, DNA, Fungal, Sanger sequencing, biology, Pneumonia, Pneumocystis, MESH : Geography, MESH: Echinococcosis, Hepatic, Middle Aged, MESH: Climate, MESH : Risk Factors, MESH: Case-Control Studies, MESH : Incidence, 3. Good health, MESH : Residence Characteristics, symbols, Female, Bronchoalveolar Lavage Fluid, Adult, MESH : Case-Control Studies, MESH: Population Density, Molecular Sequence Data, Locus (genetics), Real-Time Polymerase Chain Reaction, Microbiology, DNA, Mitochondrial, MESH: Multivariate Analysis, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, symbols.namesake, Pneumocystis jirovecii, Humans, MESH : Disease Outbreaks, MESH : Population Density, Allele, MESH : France, Genotyping, Alleles, DNA Primers, MESH : Foxes, MESH: Echinococcus multilocularis, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Foxes, MESH: Humans, MESH : Seasons, MESH : Humans, MESH : Multivariate Analysis, MESH : Climate, Ribosomal RNA, biology.organism_classification, Molecular biology, MESH: France, RNA, Ribosomal, Genome, Mitochondrial, MESH : Animals, MESH : Echinococcosis, Hepatic, MESH: Seasons
Abstract: International audience; We designed a single nucleotide primer extension (SNaPshot) assay for Pneumocystis jirovecii genotyping, targeting mt85 SNP of the mitochondrial large subunit ribosomal RNA locus, to improve minority allele detection. We then analyzed 133 consecutive bronchoalveolar lavage (BAL) fluids tested positive for P. jirovecii DNA by quantitative real-time PCR, obtained from two hospitals in different locations (Hospital 1 [n = 95] and Hospital 2 [n = 38]). We detected three different alleles, either singly (mt85C: 39.1%; mt85T: 24.1%; mt85A: 9.8%) or together (27%), and an association between P. jirovecii mt85 genotype and the patient's place of hospitalization (p = 0.011). The lowest fungal loads (median = 0.82 × 10(3) copies/μl; range: 15-11 × 10(3) ) were associated with mt85A and the highest (median = 1.4 × 10(6) copies/μl; range: 17 × 10(3) -1.3 × 10(7) ) with mt85CTA (p = 0.010). The ratios of the various alleles differed between the 36 mixed-genotype samples. In tests of serial BALs (median: 20 d; range 4-525) from six patients with mixed genotypes, allele ratio changes were observed five times and genotype replacement once. Therefore, allele ratio changes seem more frequent than genotype replacement when using a SNaPshot assay more sensitive for detecting minority alleles than Sanger sequencing. Moreover, because microscopy detects only high fungal loads, the selection of microscopy-positive samples may miss genotypes associated with low loads.
Published: 2015

39. Muscle diffusion of liposomal amphotericin B and posaconazole in critically ill burn patients receiving continuous hemodialysis

Author: B. Denis, Matthieu Legrand, Mourad Benyamina, Quentin Ressaire, Alexandre Mebazaa, Véronique Maurel, M. Chaouat, Christophe Padoin, Axelle Ferry, Sabri Soussi, Alexandre Alanio, Maurice Mimoun, Service d’anesthésie-réanimation [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de toxicologie - Hôpital Avicenne, Hôpital Avicenne [AP-HP], Service de Chirurgie Plastique et Reconstruction, 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), Université Paris Diderot - Paris 7 (UPD7), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Mycologie moléculaire, Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], The work was supported by a grant from la Fondation des ‘‘Gueules Cassées’’, AP-HP Hôpital Saint-Louis, AP-HP Groupe Hospitalier Avicenne, 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), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Posaconazole, Antifungal Agents, Critical Illness, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, 030226 pharmacology & pharmacy, Diffusion, 03 medical and health sciences, 0302 clinical medicine, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Renal Dialysis, Amphotericin B, medicine, Mucormycosis, Humans, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, 030306 microbiology, business.industry, Critically ill, Muscles, Triazoles, 3. Good health, Continuous hemodialysis, Anesthesia, Critical illness, Liposomes, Liposomal amphotericin, business, Burns, medicine.drug
Abstract: International audience; no abstract
Published: 2015

40. New Short Tandem Repeat-Based Molecular Typing Method for Pneumocystis jirovecii Reveals Intrahospital Transmission between Patients from Different Wards

Author: Alexandre Alanio, Emmanuel Raffoux, Sandrine Valade, Véronique Delcey, Maud Gits-Muselli, Jean Menotti, Nathalie De Castro, Samia Hamane, Anne Bergeron, Jean-Michel Molina, Stéphane Bretagne, Nicolas Guigue, Marie-Noëlle Peraldi, 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), Service de transplantation rénale, Université Paris Diderot - Paris 7 (UPD7), Service des Maladies Infectieuses et Tropicales [CHU Saint Louis], Service de Médecine Interne, Hôpital Lariboisière-Fernand-Widal [APHP], Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Service d'hématologie biologique, 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), Service de pneumologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service de réanimation médicale, Institut Pasteur [Paris], Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Hôpital Lariboisière, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Opportunistic infection, [SDV]Life Sciences [q-bio], Pneumocystis pneumonia, Pneumocystis carinii, Genotype, 80 and over, Child, DNA, Fungal, Pneumocystis jirovecii, Aged, 80 and over, 0303 health sciences, Multidisciplinary, Genome, biology, Pneumonia, Pneumocystis, Middle Aged, 3. Good health, Phylogeography, Fungal, Child, Preschool, Medicine, Microsatellite, Genome, Fungal, Research Article, Adult, Adolescent, Science, Opportunistic Infections, 03 medical and health sciences, Tandem repeat, medicine, Humans, Allele, Preschool, Genotyping, 030304 developmental biology, Aged, 030306 microbiology, Pneumocystis, Sputum, Infant, DNA, Pneumonia, biology.organism_classification, medicine.disease, Virology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Microsatellite Repeats
Abstract: International audience; Pneumocystis pneumonia is a severe opportunistic infection in immunocompromised patients caused by the unusual fungus Pneumocystis jirovecii. Transmission is airborne, with both immunocompromised and immunocompetent individuals acting as a reservoir for the fungus. Numerous reports of outbreaks in renal transplant units demonstrate the need for valid genotyping methods to detect transmission of a given genotype. Here, we developed a short tandem repeat (STR)-based molecular typing method for P. jirovecii. We analyzed the P. jirovecii genome and selected six genomic STR markers located on different contigs of the genome. We then tested these markers in 106 P. jirovecii PCR-positive respiratory samples collected between October 2010 and November 2013 from 91 patients with various underlying medical conditions. Unique (one allele per marker) and multiple (more than one allele per marker) genotypes were observed in 34 (32%) and 72 (68%) samples, respectively. A genotype could be assigned to 55 samples (54 patients) and 61 different genotypes were identified in total with a discriminatory power of 0.992. Analysis of the allelic distribution of the six markers and minimum spanning tree analysis of the 61 genotypes identified a specific genotype (Gt21) in our hospital, which may have been transmitted between 10 patients including six renal transplant recipients. Our STR-based molecular typing method is a quick, cheap and reliable approach to genotype Pneumocystis jirovecii in hospital settings and is sensitive enough to detect minor genotypes, thus enabling the study of the transmission and pathophysiology of Pneumocystis pneumonia.
Published: 2015

41. Importance of operational factors in the reproducibility of Aspergillus galactomannan enzyme immune assay

Author: Alexandre Alanio, Stéphane Bretagne, Marc Tabouret, Samia Hamane, Nicolas Guigue, Samuel Lardeux, 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), Bio-Rad., Mycologie moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris], and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, medicine.medical_specialty, Antigens, Fungal, [SDV]Life Sciences [q-bio], Coefficient of variation, lcsh:Medicine, Enzyme-Linked Immunosorbent Assay, Aspergillosis, Gastroenterology, Aspergillus fumigatus, Mannans, 03 medical and health sciences, Galactomannan, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, medicine, Humans, False Positive Reactions, 030212 general & internal medicine, Antigens, lcsh:Science, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 0303 health sciences, Reproducibility, Aspergillus, Multidisciplinary, biology, Adult patients, 030306 microbiology, lcsh:R, Galactose, Reproducibility of Results, Aspergillus Ag, biology.organism_classification, medicine.disease, 3. Good health, Fungal, chemistry, Immunology, lcsh:Q, Research Article
Abstract: International audience; BACKGROUND: The Platelia Aspergillus Ag assay (Bio-Rad) is designed for detecting Aspergillus galactomannan (GM) and is widely used for diagnosing invasive aspergillosis but is hampered by variable occurrences of unreproducible positive results. Frequency and origin of these unreproducible results have not been formally studied. METHODS: Different technicians simultaneously performed four tests on 550 consecutive sera from adult patients (Test#1-Test#2 for extraction#1 and Test#3-Test#4 for extraction#2). The samples were classified as confirmed negative [all tests with GM optical density index (GM-ODI) \textless0.5], confirmed positive (all tests with GM-ODI ≥0.5), extraction unreproducible positive (Test#1 and Test#2 ODIs ≥0.5, and Test#3 and Test#4 GM-ODIs \textless0.5, or conversely), and ELISA unreproducible positive (only one test with GM-ODI ≥0.5). The samples with positive and negative GM-ODIs within the assay coefficient of variation values were classified as non-conclusive. Four similar additional tests were performed after ≤72h storage at 4 °C and a new GM test after 8 months at -20 °C. RESULTS: Five-hundred-twenty sera (94.5%) were confirmed negative, 15 (2.7%) confirmed positive, 4 (0.7%) extraction unreproducible positive, 6 (1.1%) ELISA unreproducible positive, and 5 (0.9%) non-conclusive. Upon retesting, the unreproducible positive results turned negative except for one which turned non-conclusive. The confirmed positive and non-conclusive had similar GM-ODIs (p\textgreater0.4) upon retesting after storage ≤72h at 4 °C (n = 20) or eight months at -20 °C (n = 17). CONCLUSIONS: Operational unreproducible positives represent 33% of the GM-positive results and a second sample evaluation appears mandatory to avoid useless investigations or treatments. When operational artifacts are excluded, GM remains stable at standard storage conditions.
Published: 2015

42. Utility of adding Pneumocystis jirovecii DNA detection in nasopharyngeal aspirates in immunocompromised adult patients with febrile pneumonia

Author: Olivier Peyrony, Alexandre Alanio, Samia Hamane, Nathalie De Castro, Stéphane Bretagne, Nicolas Guigue, Jérôme LeGoff, Jean Menotti, 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), Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Mycologie moléculaire, Service de maladies infectieuses et tropicales [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-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), Service des urgences, Hopital Saint-Louis [AP-HP] (AP-HP), Laboratoire de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), 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), AP-HP Hôpital Saint-Louis, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Male, [SDV]Life Sciences [q-bio], Pneumocystis pneumonia, Pneumocystis carinii, 0302 clinical medicine, Nasopharynx, Pneumocystosis, 80 and over, 030212 general & internal medicine, Fever of unknown origin, DNA, Fungal, Pneumocystis jirovecii, Aged, 80 and over, 0303 health sciences, biology, medicine.diagnostic_test, nasopharyngeal aspirates, General Medicine, Middle Aged, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, Fungal, Molecular Diagnostic Techniques, Female, Original Article, influenza, Adult, Adolescent, Lymphoproliferative disorders, Real-Time Polymerase Chain Reaction, DNA, Ribosomal, Fever of Unknown Origin, 03 medical and health sciences, Young Adult, stomatognathic system, medicine, Humans, quantitative real-time PCR, Aged, Ribosomal, 030306 microbiology, DNA, Pneumonia, medicine.disease, biology.organism_classification, Virology, Bronchoalveolar lavage, RNA, Ribosomal, Immunology, RNA, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Detection of viral and bacterial DNA in nasopharyngeal aspirates (NPAs) is now a routine practice in emergency cases of febrile pneumonia. We investigated whether Pneumocystis jirovecii DNA could also be detected in these cases by conducting retrospective screening of 324 consecutive NPAs from 324 adult patients (198 or 61% were immunocompromised) admitted with suspected pulmonary infections during the 2012 influenza epidemic season, using a real-time quantitative polymerase chain reaction (PCR) assay (PjqPCR), which targets the P. jirovecii mitochondrial large subunit ribosomal RNA gene. These NPAs had already been tested for 22 respiratory pathogens (18 viruses and 4 bacteria), but we found that 16 NPAs (4.9%) were PjqPCR-positive, making P. jirovecii the fourth most prevalent of the 23 microorganisms in the screen. Eleven of the 16 PjqPCR-positive patients were immunocompromised, and five had underlying pulmonary conditions. Nine NPAs were also positive for another respiratory pathogen. Six had PjqPCR-positive induced sputa less than 3 days after the NPA procedure, and five were diagnosed with pneumocystis pneumonia (four with chronic lymphoproliferative disorders and one AIDS patient). In all six available pairs quantification of P. jirovecii DNA showed fewer copies in NPA than in induced sputum and three PjqPCR-negative NPAs corresponded to PjqPCR-positive bronchoalveolar lavage fluids, underscoring the fact that a negative PjqPCR screen does not exclude a diagnosis of pneumocystosis. Including P. jirovecii DNA detection to the panel of microorganisms included in screening tests used for febrile pneumonia may encourage additional investigations or support use of anti-pneumocystis pneumonia prophylaxis in immunocompromised patients.
Published: 2015

43. Azole resistance of Aspergillus fumigatus in immunocompromised patients with invasive aspergillosis

Author: Régis Peffault de Latour, Alexandre Alanio, Blandine Denis, Emmanuel Raffoux, Anne Bergeron, Sandy Amorim, Jean Menotti, Sophie Touratier, Samia Hamane, Stéphane Bretagne, Centre National de Référence des Mycoses invasives et antifongiques - Mycologie moléculaire (CNRMA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), 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), Mycologie moléculaire, Service d'hématologie biologique, 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), and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Azoles, 0301 basic medicine, Posaconazole, Letter, Antifungal Agents, Epidemiology, [SDV]Life Sciences [q-bio], Drug Resistance, lcsh:Medicine, Disease, Drug resistance, Aspergillosis, Aspergillus fumigatus, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, 3. Good health, immunocompromised, Aspergillus, Fungal, Infectious Diseases, Population Surveillance, France, medicine.symptom, medicine.drug, Microbiology (medical), medicine.medical_specialty, Itraconazole, 030106 microbiology, Azole resistance, lcsh:Infectious and parasitic diseases, Microbiology, 03 medical and health sciences, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Drug Resistance, Fungal, medicine, Humans, lcsh:RC109-216, antimicrobial resistance, Letters to the Editor, Azole Resistance of Aspergillus fumigatus in Immunocompromised Patients with Invasive Aspergillosis, Etest, Voriconazole, invasive aspergillosis, business.industry, the Netherlands, lcsh:R, medicine.disease, biology.organism_classification, Spore, Sputum, fungi, business
Abstract: To the Editor: First-line antifungal therapy for invasive aspergillosis (IA) is voriconazole, which is challenged by the emergence of azole resistance (1). A recent article reported a 3.2% prevalence of Aspergillus fumigatus isolates that are resistant to azole from 3,788 isolates screened in Europe (2). Of the 1,911 patients from whom the isolates were collected, IA developed in 10 (3 proven, 1 probable, 6 possible). Prevalence of azole-resistant A. fumigatus disease among patient populations at risk of IA was unavailable. As described (3), we screened every A. fumigatus isolate recovered from respiratory specimens from patients with probable or proven IA in our hospital in Paris, France, during January 2012–December 2014. Every isolate recovered from 2% malt extract agar plates or Sabouraud dextrose agar slants (Bio-Rad, Marnes-la-Coquette, France) was incubated at 30°C and tested as individual isolates or multiple ones from a single sample by using itraconazole, voriconazole, and posaconazole Etest strips (bioMerieux, Marcy l’Etoile, France). Resistance was assessed for MICs >2.0 µg/µL for voriconazole and itraconazole and >0.25 µg/µL for posaconazole by using European Committee on Antimicrobial Susceptibility Testing clinical breakpoints for fungi (http://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/AFST/Antifungal_breakpoints_v_7.0.pdf). Every 4 months, a local multidisciplinary medical team classified each IA case by using the 2008 criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (4). For 148 patients (127 with hematologic malignancies and 21 with other conditions), the team recorded 152 episodes: 9 proven and 143 probable IA episodes. Possible IA was not analyzed because of a lack of microbiologic criteria. For 51 probable IA episodes, galactomannan positivity in blood or bronchoalveolar lavage fluid samples was the only microbiologic criterion used for classification. Cultures of respiratory samples (i.e., bronchoalveolar lavage fluid, tracheal aspirate, and sputum) or biopsies were positive for 99 episodes: 68 with A. fumigatus isolates and 31 with other Aspergillus spp. isolates. Among the 68 A. fumigatus isolates, 1 (1.5%) associated with probable IA was resistant to azoles (5). The isolate harbored the TR34/L98H mutation (5), leading to a rate of IA caused by azole-resistant A. fumigatus of 0.7% (1/152) for total episodes recorded and 1% (1/99) for culture-positive episodes only. Nineteen (36%) of 53 culture-negative patients and 35 (37%) of 95 culture-positive patients died. Azole resistance of A. fumigatus warrants specific surveillance in hospitals treating immunocompromised patients. Prevalence of resistant isolates can differ by hospital location and underlying disease (e.g., immunodeficiency vs. chronic lung diseases). When focusing on patients with probable or proven IA, we did not observe an emergence of azole-resistant A. fumigatus isolates during 2006–2009 (3) and 2012–2014 in France. Consequently, our center does not question the use of voriconazole as first-line treatment or of posaconazole as prophylaxis.
Published: 2016

44. Decreasing incidence of cryptococcal meningitis in West Africa in the era of highly active antiretroviral therapy

Author: Athanase Millogo, Olivier Lortholary, Stéphane Bretagne, Sanata Bamba, Robert T. Guiguemdé, Adrien Sawadogo, Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Institut Pasteur [Paris], Centre d'infectiologie Necker-Pasteur [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP]
Subjects: Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, Opportunistic infection, Immunology, HIV Infections, Meningitis, Cryptococcal, Hospitals, University, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), Antiretroviral Therapy, Highly Active, Burkina Faso, parasitic diseases, Epidemiology, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Immunology and Allergy, 030212 general & internal medicine, Sida, health care economics and organizations, Mycosis, 0303 health sciences, AIDS-Related Opportunistic Infections, biology, 030306 microbiology, business.industry, Incidence, Incidence (epidemiology), Middle Aged, medicine.disease, biology.organism_classification, 3. Good health, Infectious Diseases, Cryptococcosis, [SDV.IMM]Life Sciences [q-bio]/Immunology, population characteristics, Female, business, Meningitis, geographic locations
Abstract: International audience; Cryptococcosis remains a major opportunistic infection in AIDS in sub-Saharan Africa, but few data exist from its western part. We report data from Bobo Dioulasso University Hospital, Bobo-Dioulasso, Burkina Faso, with a steady decline from 14 to two cases per year from 2002 to 2010 which contrasts with the increase (from 147 to 3940) of patients on antiretroviral therapy (ART). Better ART availability decreases the incidence of cryptococcosis in Burkina Faso.
Published: 2012

45. An overview of using fungal DNA for the diagnosis of invasive mycoses

Author: P. Lewis White, Alexandre Alanio, Lottie Brown, Mario Cruciani, Ferry Hagen, Rebecca Gorton, Michaela Lackner, Laurence Millon, C. Oliver Morton, Riina Rautemaa-Richardson, Rosemary A. Barnes, J Peter Donnelly, Juergen Loffler, Public Health Wales [Cardiff, Royaume uni], 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), Centre National de Référence Mycoses Invasives et Antifongiques - National Reference Center Invasive Mycoses & Antifungals (CNRMA), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Manchester University NHS Foundation Trust (MFT), Fungal PCR Initiative (FPCRI), University Medical Center [Utrecht], National Health Laboratory Services, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), 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), Western Sydney University, Cardiff University, and University Hospital Wuerzburg / Universitätsklinikum Würzburg
Subjects: MESH: Fungi, mucorales PCR, MESH: Molecular Diagnostic Techniques, Polymerase Chain Reaction, Pathology and Forensic Medicine, Genetics, Humans, candida PCR, Fungi/genetics, DNA, Fungal, Molecular Biology, aspergillus PCR, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Fungal/genetics, PCP PCR, Fungi, MESH: Polymerase Chain Reaction, DNA, fungal PCR, MESH: DNA, Fungal, Molecular Diagnostic Techniques, Molecular Medicine, Invasive fungal disease, Invasive Fungal Infections/diagnosis, Invasive Fungal Infections, MESH: Invasive Fungal Infections
Abstract: Introduction: Fungal PCR has undergone considerable standardization and together with the availability of commercial assays, external quality assessment schemes and extensive performance validation data, is ready for widespread use for the screening and diagnosis of invasive fungal disease (IFD).Areas Covered: Drawing on the experience and knowledge of the leads of the various working parties of the Fungal PCR initiative, this review will address general considerations concerning the use of molecular tests for the diagnosis of IFD, before focussing specifically on the technical and clinical aspects of molecular testing for the main causes of IFD and recent technological developments.Expert Opinion: For infections caused by Aspergillus, Candida and Pneumocystis jirovecii, PCR testing is recommended, combination with serological testing will likely enhance the diagnosis of these diseases. For other IFD (e.g. Mucormycosis) molecular diagnostics, represent the only non-classical mycological approach towards diagnoses and continued performance validation and standardization has improved confidence in such testing. The emergence of antifungal resistance can be diagnosed, in part, through molecular testing. Next-generation sequencing has the potential to significantly improve our understanding of fungal phylogeny, epidemiology, pathogenesis, mycobiome/microbiome and interactions with the host, while identifying novel and existing mechanisms of antifungal resistance and novel diagnostic/therapeutic targets.
Published: 2022

46. Solid-state NMR molecular snapshots of Aspergillus fumigatus cell wall architecture during a conidial morphotype transition

Author: Gaëlle Lamon, Alons Lends, Isabel Valsecchi, Sarah Sze Wah Wong, Vincent Duprès, Frank Lafont, James Tolchard, Christine Schmitt, Adeline Mallet, Axelle Grélard, Estelle Morvan, Erick J. Dufourc, Birgit Habenstein, J. Iñaki Guijarro, Vishukumar Aimanianda, Antoine Loquet, Chimie et Biologie des Membranes et des Nanoobjets (CBMN), Université de Bordeaux (UB)-École Nationale d'Ingénieurs des Travaux Agricoles - Bordeaux (ENITAB)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Européen de Chimie et Biologie (IECB), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Plateforme Technologique de RMN Biologique et HDX-MS - Biological NMR and HDX-MS Technological Platform, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Mycologie moléculaire - Molecular Mycology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Plate-forme de bioimagerie ultrastructurale - Ultrastructural BioImaging Core Facility, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), We are grateful for the support for equipment from the French Government Programme Investissements d’Avenir France BioImaging (FBI, Agence Nationale de la Recherche, N° ANR-10-INSB-04-01) and the French Government Investissement d’Avenir programme, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases' (ANR-10-LABX-62-IBEID). We thank the ANR grants ANR-16-CE11-0020-02 to I.G., A.L., and V.A., ANR-21-CE17-0032-01 to V.A.), as well as the Swiss National Science Foundation (for early postdoc mobility project P2EZP2_184258 to A. Lends. This work has benefited from the Biophysical and Structural Chemistry Platform at Institut Européen de Chimie et Biologie IECB, Centre National de la Recherche Scientifique CNRS Unité d'Appui et de Recherche UAR 3033, INSERM US001, and the CNRS (IR‐RMN FR3050 and Infranalytics FR2054). We also acknowledge the access to the confocal microscope of the Ultrastructural BioImaging core facility of the Institut Pasteur, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-16-CE11-0020,FUNHYDRO,Amyloïdes fonctionnels formés par les hydrophobines du pathogène fongique Aspergillus fumigatus(2016), and ANR-21-CE17-0032,FUNPOLYVAC,Explorer les polysaccharides fongiques de la paroi cellulaire pour les immunothérapies(2021)
Subjects: Multidisciplinary, germination, Aspergillus fumigatus, cell wall dynamics, [SDV]Life Sciences [q-bio], solid-state NMR, conidium
Abstract: While establishing an invasive infection, the dormant conidia of Aspergillus fumigatus transit through swollen and germinating stages, to form hyphae. During this morphotype transition, the conidial cell wall undergoes dynamic remodeling, which poses challenges to the host immune system and antifungal drugs. However, such cell wall reorganization during conidial germination has not been studied so far. Here, we explored the molecular rearrangement of Aspergillus fumigatus cell wall polysaccharides during different stages of germination. We took advantage of magic-angle spinning NMR to investigate the cell wall polysaccharides, without employing any destructive method for sample preparation. The breaking of dormancy was associated with a significant change in the molar ratio between the major polysaccharides β-1,3-glucan and α-1,3-glucan, while chitin remained equally abundant. The use of various polarization transfers allowed the detection of rigid and mobile polysaccharides; the appearance of mobile galactosaminogalactan was a molecular hallmark of germinating conidia. We also report for the first time highly abundant triglyceride lipids in the mobile matrix of conidial cell walls. Water to polysaccharides polarization transfers revealed an increased surface exposure of glucans during germination, while chitin remained embedded deeper in the cell wall, suggesting a molecular compensation mechanism to keep the cell wall rigidity. We complement the NMR analysis with confocal and atomic force microscopies to explore the role of melanin and RodA hydrophobin on the dormant conidial surface. Exemplified here using Aspergillus fumigatus as a model, our approach provides a powerful tool to decipher the molecular remodeling of fungal cell walls during their morphotype switching.
Published: 2023

47. 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

48. Posttraumatic mucormycosis: a nationwide study in France and review of the literature

Author: Emmanuel GYAN, Norbert IFRAH, Stéphane Bretagne, Frédéric GRENOUILLET, Marcio Junior, Sophie Cassaing, Jean-Francois Viel, Bruno MARCHOU, Raoul Herbrecht, Daniel Ajzenberg, Catherine Quantin, Cedric Arvieux, Mikael Hivelin, Stéphane Ranque, Boualem Sendid, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris], Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Chirurgie plastique, reconstructrice et esthétique [Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5), Service de parasitologie et de mycologie médicales [Amiens], Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Matrice extracellulaire et dynamique cellulaire - UMR 7369 (MEDyC), SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Reims (CHU Reims), Pathogénie des infections systémiques (UMR_S 570), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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)-Université Paris Descartes - Paris 5 (UPD5), Laboratoire de parasitologie et de mycologie médicales [CHU Amiens], CHU Amiens-Picardie, Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP), Université de Reims Champagne-Ardenne (URCA)-SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université de Picardie Jules Verne ( UPJV ) -CHU Amiens-Picardie, Matrice extracellulaire et dynamique cellulaire - UMR 7369 ( MEDyC ), Centre National de la Recherche Scientifique ( CNRS ) -Université de Reims Champagne-Ardenne ( URCA ) -SFR CAP Santé (Champagne-Ardenne Picardie Santé), Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ) -Université de Reims Champagne-Ardenne ( URCA ) -Université de Picardie Jules Verne ( UPJV ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Pathogénie des infections systémiques ( UMR_S 570 ), and Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Aged, Poison control, MESH: Aged, 80 and over, MESH : Child, MESH: Child, MESH : Female, Young adult, MESH: Aged, MESH: Middle Aged, biology, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, MESH : Adult, MESH : Wounds and Injuries, 3. Good health, MESH : Mucorales, MESH: Young Adult, Cohort, Coinfection, MESH: Mucorales, Antifungal, medicine.medical_specialty, medicine.drug_class, MESH : Male, MESH : Young Adult, MESH : Adolescent, Internal medicine, Injury prevention, medicine, MESH : Middle Aged, MESH : Mucormycosis, MESH : France, MESH : Aged, 80 and over, MESH: Mucormycosis, MESH: Adolescent, MESH: Humans, business.industry, MESH : Humans, Mucormycosis, MESH: Adult, Saksenaea vasiformis, medicine.disease, biology.organism_classification, MESH: Male, Surgery, MESH: France, MESH: Wounds and Injuries, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; Data on clinical, mycologic characteristics, and outcome of posttraumatic mucormycosis are scarce and often limited to case reports. From the French nationwide "RetroZygo" study, we compared posttraumatic mucormycosis cases with other forms of mucormycosis. We also reviewed reports of posttraumatic mucormycosis in the English-language literature from 1993 to 2013. We included all proven or probable cases for which underlying condition, route of infection, surgical and antifungal treatments, and outcome were detailed. From our cohort, posttraumatic mucormycosis (n = 16) differed significantly from other forms (n = 85) by rarity of underlying disease (31.2% vs 81%, p
Published: 2014

49. Last Generation Triazoles for Imported Eumycetoma in Eleven Consecutive Adults

Author: Cédric Arvieux, Marie-Elisabeth Bougnoux, Karima Amazzough, Samuel Pineau, Yoann Crabol, Valérie Zeller, Stéphane Barete, Marc Lecuit, Olivier Lortholary, C. Maunoury, Fanny Lanternier, Sylvain Poirée, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie et imagerie médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Parasitologie-Mycologie, Service de Microbiologie [Hôpital Necker-Enfants-Malades, Paris], Assistance Publique - Hôpitaux de Paris, Médecine nucléaire [CHU HEGP], 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Médecine interne [Diaconesses Croix Saint-Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Service de maladies infectieuses et tropicales [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), 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 National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), HAL UPMC, Gestionnaire, Service de dermatologie et allergologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Unité de Parasitologie-Mycologie, Service de Microbiologie, Hôpital Necker-Enfants-Malades, Médecine nucléaire [CHU Pompidou], Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Dermatologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Maladies infectieuses et réanimation médicale [CHU Rennes], Université de Nantes ( UN ) -Hôtel-Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Biologie des Infections, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Institut Pasteur [Paris], Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des maladies infectieuses et réanimation médicale [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Imagine - Institut des maladies génétiques (IHU), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - AP-HP Hôpital Necker - Enfants Malades [Paris], Centre d’Infectiologie Necker Pasteur, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker - Enfants Malades - Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Tenon [APHP], Service des maladies infectieuses et réanimation médicale, Université de Rennes 1 (UR1) - Hôpital Pontchaillou, Université de Nantes (UN) - Hôtel-Dieu - CHU Nantes, Institut Pasteur [Paris] - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Mycoses invasives et antifongiques-Mycologie moléculaire (CNRMA), and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, Posaconazole, Pathology, Antifungal Agents, beta-Glucans, Madurella, 0302 clinical medicine, Fusarium, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Exophiala, Medicine and Health Sciences, Child, Skin, 0303 health sciences, medicine.diagnostic_test, biology, lcsh:Public aspects of medicine, Fungal Diseases, Magnetic Resonance Imaging, 3. Good health, [SDV] Life Sciences [q-bio], [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Treatment Outcome, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Proteoglycans, Radiology, medicine.drug, Research Article, Adult, medicine.medical_specialty, lcsh:Arctic medicine. Tropical medicine, [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Adolescent, lcsh:RC955-962, 030231 tropical medicine, Eumycetoma, 03 medical and health sciences, Young Adult, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Fluorodeoxyglucose F18, medicine, Subcutaneous Mycoses, Humans, Retrospective Studies, Fluorodeoxyglucose, Voriconazole, 030306 microbiology, business.industry, Soft Tissue Infections, [ SDV.SP.MED ] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Madurella mycetomatis, Public Health, Environmental and Occupational Health, Magnetic resonance imaging, Exophiala jeanselmei, lcsh:RA1-1270, Triazoles, medicine.disease, biology.organism_classification, Mycetoma, Positron-Emission Tomography, business
Abstract: Background Optimal management of eumycetoma, a severely debilitating chronic progressive fungal infection of skin, disseminating to bone and viscera, remains challenging. Especially, optimal antifungal treatment and duration are ill defined. Methodology/Principal Findings We conducted a monocentric retrospective study of 11 imported cases of eumycetoma treated by voriconazole or posaconazole for at least 6 months. Response to treatment was assessed through evolution of clinical and magnetic resonance imaging (MRI). (1→3) ß-D-glucan (BG) and positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) results were also assessed. Identified species were Fusarium solani complex (n = 3); Madurella mycetomatis, (n = 3), and Exophiala jeanselmei, (n = 1). Moreover, two coelomycetes and one phaeohyphomycetes strains without species identification were retrieved. Serum BG and PET/CT were abnormal in 7/8 and 6/6 patients tested, respectively. Patients received last generation azoles for a mean duration of 25.9±18 months. Complete response (major clinical and MRI improvement) was observed in 5/11 patients, partial response (minor MRI improvement or stable MRI findings) in 5 and failure (MRI evidence of disease progression) in one, with a 73±39 [6–132] months mean follow-up. Relapse occurred in 2 patients after treatment discontinuation. Optimal outcome was associated with fungal species, initiation of last generation triazole therapy (, Author Summary Eumycetoma is a severe chronic progressive fungal infection of skin and ultimately bone or viscera that affect mainly people with low economic status. Optimal treatment of this condition relies on medical and often surgical therapy and remains challenging because of lack of gold standard therapy and high rate of relapse after treatment discontinuation. In this retrospective study we assessed whether modern triazoles (voriconazole and posaconazole) suited to eumycetoma treatment and if tailored treatment duration, based on serial evaluation of a serum biomarker of fungal infection (Serum (1→3) ß-D-Glucan, (BD)), magnetic resonance imaging (MRI) or positron emission tomography using [18F] fluorodeoxyglucose (PET/CT) would be useful. We found that modern triazoles were efficient treatments of eumycetoma, allowing complete or partial response in 10/11 of patients, without significant side effects. Moreover, patients with treatment discontinuation based on normalization of BD, MRI or PET/CT seemed to have better long-term outcome than those with clinical cure but still abnormal BD or imaging results.
Published: 2014

50. Worrisome trends in incidence and mortality of candidemia in intensive care units (Paris area, 2002-2010)

Author: Arnaud Fontanet, Charlotte Renaudat, Françoise Dromer, Olivier Lortholary, Yoann Madec, Michel Wolff, Stéphane Bretagne, Karine Sitbon, Lise Denoeud-Ndam, Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire ( CNRMA ), Institut Pasteur [Paris], Centre d'infectiologie Necker-Pasteur [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Epidémiologie des Maladies Emergentes, Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Institut Pasteur [Paris]-Pasteur-Cnam risques infectieux et émergents ( PACRI ), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Reanimation Médicale et Infectieuse [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat-Claude Bernard, Conservatoire National des Arts et Métiers - Paris ( CNAM Paris ), Conservatoire National des Arts et Métiers [CNAM] ( CNAM ), Laboratoire de Parasitologie-Mycologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], The YEASTS program was supported in part by Institut de Veille Sanitaire and Institut Pasteur, Centre National de Référence Mycologie et Antifongiques-Mycologie Moléculaire (CNRMA), Institut Pasteur [Paris] (IP), 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), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie des Maladies Emergentes - Emerging Diseases Epidemiology, Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM)
Subjects: Male, Pediatrics, Antifungal Agents, Time Factors, Original, Epidemiology, [SDV]Life Sciences [q-bio], Critical Care and Intensive Care Medicine, law.invention, Echinocandins, chemistry.chemical_compound, 0302 clinical medicine, Hematological malignancy, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, 80 and over, 030212 general & internal medicine, Prospective Studies, Fluconazole, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Candida, Aged, 80 and over, 0303 health sciences, education.field_of_study, Mortality rate, Incidence (epidemiology), Incidence, Middle Aged, Intensive care unit, 3. Good health, Intensive Care Units, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Non-albicans species, medicine.drug, Adult, medicine.medical_specialty, Paris, Population, Risk Assessment, 03 medical and health sciences, Intensive care, medicine, Humans, education, Aged, [ SDV ] Life Sciences [q-bio], 030306 microbiology, business.industry, Candidemia, Odds ratio, bacterial infections and mycoses, chemistry, Caspofungin, business
Abstract: International audience; PURPOSE: To analyze trends in incidence and mortality of candidemia in intensive care units (ICUs) vs. non-ICU hospitalized patients and to determine risk factors for infection by specific species and for death. METHODS: Active hospital-based surveillance program of incident episodes of candidemia due to common species in 24 tertiary care hospitals in the Paris area, France between October 2002 and September 2010. RESULTS: Among 2,507 adult cases included, 2,571 Candida isolates were collected and species were C. albicans (56 %), C. glabrata (18.6 %), C. parapsilosis (11.5 %), C. tropicalis (9.3 %), C. krusei (2.9 %), and C. kefyr (1.8 %). Candidemia occurred in ICU in 1,206 patients (48.1 %). When comparing ICU vs. non-ICU patients, the former had significantly more frequent surgery during the past 30 days, were more often preexposed to fluconazole and treated with echinocandin, and were less frequently infected with C. parapsilosis. Risk factors and age remained unchanged during the study period. A significant increased incidence in the overall population and ICU was found. The odds of being infected with a given species in ICU was influenced by risk factors and preexposure to fluconazole and caspofungin. Echinocandins initial therapy increased over time in ICU (4.6 % first year of study, to 48.5 % last year of study, p \textless 0.0001). ICU patients had a higher day-30 death rate than non-ICU patients (odds ratio [OR] 2.12; 95 % confidence interval [CI] 1.66-2.72; p \textless 0.0001). The day-30 and early (\textlessday 8) death rates increased over time in ICU (from 41.5 % the first to 56.9 % the last year of study (p = 0.001) and 28.7-38.8 % (p = 0.0292), respectively). Independent risk factors for day-30 death in ICU were age, arterial catheter, Candida species, preexposure to caspofungin, and lack of antifungal therapy at the time of blood cultures results (p \textless 0.05). CONCLUSIONS: The availability of new antifungals and the publication of numerous guidelines did not prevent an increase of candidemia and death in ICU patients in the Paris area.
Published: 2014

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