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1. A global chromoblastomycosis strategy and development of the global chromoblastomycosis working group.

Author

Dallas J Smith, Flávio Queiroz-Telles, Fahafahantsoa Rapelanoro Rabenja, Roderick Hay, Alexandro Bonifaz, Marlous L Grijsen, Romain Blaizot, Fernando Messina, Yinggai Song, Shawn R Lockhart, Alexander Jordan, Alyson M Cavanaugh, Anastasia P Litvintseva, Tom Chiller, Marco Schito, Sybren de Hoog, Vania Aparecida Vicente, Muriel Cornet, Daniel Argaw Dagne, Lala S Ramarozatovo, Conceição de Maria Pedrozo E Silva de Azevedo, and Daniel Wagner C L Santos

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Chromoblastomycosis, an implantation mycosis, is a neglected tropical disease that causes decreased quality of life, stigma, and disability. The global burden of disease is unknown and data on disease epidemiology and outcomes are severely limited by a lack of access to needed diagnostic tools and therapeutics. The World Health Organization outlined targets for chromoblastomycosis in the Road Map for Neglected Tropical Diseases 2021-2030, but little progress has been made in initiating and implementing an effective control program globally. This lack of guiding policy and progress led to the recent formation of a Global Chromoblastomycosis Working Group which has developed a global chromoblastomycosis strategy. We describe this strategy, which outlines specific steps needed to improve technical progress, strategy and service delivery, and enablers. Clinicians, researchers, public and government officials, patients, and policy makers can align their time, expertise, and resources to improve the lives of communities affected by chromoblastomycosis through this strategy.

Published
2024
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2. Inulin prebiotic reinforces host cancer immunosurveillance via ɣδ T cell activation

Author

Emilie Boucher, Caroline Plazy, Mathias L. Richard, Antonia Suau, Irène Mangin, Muriel Cornet, Delphine Aldebert, Bertrand Toussaint, and Dalil Hannani

Subjects
ɣδ T cells, immunosurveillance, microbiota, prebiotic, inulin, Immunologic diseases. Allergy, RC581-607
Abstract

The gut microbiota is now recognized as a key parameter affecting the host’s anti-cancer immunosurveillance and ability to respond to immunotherapy. Therefore, optimal modulation for preventive and therapeutic purposes is very appealing. Diet is one of the most potent modulators of microbiota, and thus nutritional intervention could be exploited to improve host anti-cancer immunity. Here, we show that an inulin-enriched diet, a prebiotic known to promote immunostimulatory bacteria, triggers an enhanced Th1-polarized CD4+ and CD8+ αβ T cell-mediated anti-tumor response and attenuates tumor growth in three preclinical tumor-bearing mouse models. We highlighted that the inulin-mediated anti-tumor effect relies on the activation of both intestinal and tumor-infiltrating ɣδ T cells that are indispensable for αβ T cell activation and subsequent tumor growth control, in a microbiota-dependent manner. Overall, our data identified these cells as a critical immune subset, mandatory for inulin-mediated anti-tumor immunity in vivo, further supporting and rationalizing the use of such prebiotic approaches, as well as the development of immunotherapies targeting ɣδ T cells in cancer prevention and immunotherapy.

Published
2023
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3. Clinical aspects of previously treated chromoblastomycosis: A case series from Madagascar

Author

Fandresena Arilala Sendrasoa, Naina Harinjara Razanakoto, Mendrika Fifaliana Rakotoarisaona, Malalaniaina Andrianarison, Onivola Raharolahy, Tahinamandranto Rasamoelina, Irina Mamisoa Ranaivo, Moril Sata, Volatantely Ratovonjanahary, Danièle Maubon, Mala Rakoto Andrianarivelo, Muriel Cornet, Lala Soavina Ramarozatovo, and Fahafahantsoa Rapelanoro Rabenja

Subjects
Chromoblastomycosis, Cicatricial lesion, Madagascar, Infectious and parasitic diseases, RC109-216
Abstract

Objective: To describe the clinical aspects of chromoblastomycosis (CBM) presented by patients who had received incomplete antifungal treatment before consultation. Methods: A prospective study of patients with clinically suspected CBM was performed between 2013 and 2018 in the Department of Dermatology at the University Hospital Antananarivo, and during consultation campaigns. Results: Patients develop CBM over a period of more than 10 years, and many will have already received antifungals prescribed by general practitioners before consulting with a dermatologist. Such treatment obviously modifies the clinical presentation. From the 63 CBM patients in this large study, we describe 12 patients who received oral antifungals (terbinafine, griseofulvine, itraconazole, fluconazole) before consultation.The most frequent clinical aspect presented by these patients was cicatricial lesions, which are characteristically smooth and non-elevated, and enlarge by peripheral extension, with atrophic scarring at the center. Conclusion: Our study is the first to show that cicatricial lesions are a clinical aspect presented by CBM patients who received antifungals before presentation.

Published
2020
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4. Mucormycosis in intensive care unit: surgery is a major prognostic factor in patients with hematological malignancy

Author

Johanna Claustre, Romaric Larcher, Thomas Jouve, Anne-Sophie Truche, Saad Nseir, Julien Cadiet, Yoann Zerbib, Alexandre Lautrette, Jean-Michel Constantin, Pierre-Emmanuel Charles, Cedric Daubin, Remi Coudroy, Jean Dellamonica, Laurent Argaud, Pierre Phelouzat, Damien Contou, Juliette Pocquet, Guillaume Voiriot, Jean-Christophe Navellou, Pierre Lavagne, Michel Durand, Muriel Cornet, Carole Schwebel, and Nicolas Terzi

Subjects
Mucormycosis, Hematological malignancy, Intensive care unit, Surgery, Prognostic factors, Medical emergencies. Critical care. Intensive care. First aid, RC86-88.9
Abstract

Abstract Background Mucormycosis is an invasive fungal infection, with an increasing incidence especially in patients with hematological malignancies. Its prognosis is poor because of its high invasive power and its intrinsic low susceptibility to antifungal agents. We aimed to describe the epidemiology of mucormycosis in intensive care units (ICU) and evaluate the outcomes. We performed a retrospective multi-center study in 16 French ICUs between 2008 and 2017. We compared the patients who survived in ICU and the patients who did not to identify factors associated with ICU survival. Then, we focused on the subgroup of patients with hematological malignancies. Results Mucormycosis was diagnosed in 74 patients during the study period. Among them, 60 patients (81%) were immunocompromised: 41 had hematological malignancies, 9 were solid organ transplant recipients, 31 received long-term steroids, 11 had diabetes, 24 had malnutrition. Only 21 patients survived to ICU stay (28.4%) with a median survival of 22 days (Q1–Q3 = 9–106) and a survival rate at day 28 and day 90, respectively, of 35.1% and 26.4%. Survivors were significantly younger (p = 0.001), with less frequently hematological malignancies (p = 0.02), and less malnutrition (p = 0.05). Median survival in patients with hematological malignancies (n = 41) was 15 days (Q1–Q3 = 5–23.5 days). In this subgroup, curative surgery was a major factor associated with survival in multivariate analysis (odds ratio = 0.71, [0.45–0.97], p

Published
2020
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5. Endemic Chromoblastomycosis Caused Predominantly by Fonsecaea nubica, Madagascar

Author

Tahinamandranto Rasamoelina, Danièle Maubon, Malalaniaina Andrianarison, Irina Ranaivo, Fandresena Sendrasoa, Njary Rakotozandrindrainy, Fetra A. Rakotomalala, Sébastien Bailly, Benja Rakotonirina, Abel Andriantsimahavandy, Fahafahantsoa Rakato Rabenja, Mala R. Andrianarivelo, Muriel Cornet, and Lala S. Ramarozatovo

Subjects
chromoblastomycosis, dermatomycosis, fungi, fungal infections, epidemiology, prevalence, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Chromoblastomycosis is an implantation fungal infection. Twenty years ago, Madagascar was recognized as the leading focus of this disease. We recruited patients in Madagascar who had chronic subcutaneous lesions suggestive of dermatomycosis during March 2013–June 2017. Chromoblastomycosis was diagnosed in 50 (33.8%) of 148 patients. The highest prevalence was in northeastern (1.47 cases/100,000 persons) and southern (0.8 cases/100,000 persons) Madagascar. Patients with chromoblastomycosis were older (47.9 years) than those without (37.5 years) (p = 0.0005). Chromoblastomycosis was 3 times more likely to consist of leg lesions (p = 0.003). Molecular analysis identified Fonsecaea nubica in 23 cases and Cladophialophora carrionii in 7 cases. Of 27 patients who underwent follow-up testing, none were completely cured. We highlight the persistence of a high level of chromoblastomycosis endemicity, which was even greater at some locations than 20 years ago. We used molecular tools to identify the Fonsecaea sp. strains isolated from patients as F. nubica.

Published
2020
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6. Can We Improve Antifungal Susceptibility Testing?

Author

Charlotte Durand, Danièle Maubon, Muriel Cornet, Yan Wang, Delphine Aldebert, and Cécile Garnaud

Subjects
Antifungals susceptibility testing, MALDI-TOF, flow cytometry, molecular biology, computed imaging, Microbiology, QR1-502
Abstract

Systemic antifungal agents are increasingly used for prevention or treatment of invasive fungal infections, whose prognosis remains poor. At the same time, emergence of resistant or even multi-resistant strains is of concern as the antifungal arsenal is limited. Antifungal susceptibility testing (AFST) is therefore of key importance for patient management and antifungal stewardship. Current AFST methods, including reference and commercial types, are based on growth inhibition in the presence of an antifungal, in liquid or solid media. They usually enable Minimal Inhibitory Concentrations (MIC) to be determined with direct clinical application. However, they are limited by a high turnaround time (TAT). Several innovative methods are currently under development to improve AFST. Techniques based on MALDI-TOF are promising with short TAT, but still need extensive clinical validation. Flow cytometry and computed imaging techniques detecting cellular responses to antifungal stress other than growth inhibition are also of interest. Finally, molecular detection of mutations associated with antifungal resistance is an intriguing alternative to standard AFST, already used in routine microbiology labs for detection of azole resistance in Aspergillus and even directly from samples. It is still restricted to known mutations. The development of Next Generation Sequencing (NGS) and whole-genome approaches may overcome this limitation in the near future. While promising approaches are under development, they are not perfect and the ideal AFST technique (user-friendly, reproducible, low-cost, fast and accurate) still needs to be set up routinely in clinical laboratories.

Published
2021
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7. Evaluation of a Prototype of a Novel Galactomannan Sandwich Assay Using the VIDAS® Technology for the Diagnosis of Invasive Aspergillosis

Author

Salomé Gallet, Cécile Garnaud, Céline Dragonetti, Sophie Rivoiron, Odile Cognet, Yuping Guo, Mylène Lesénéchal, Danièle Maubon, and Muriel Cornet

Subjects
diagnosis, invasive aspergillosis, galactomannan, single-sample test, VIDAS®, Microbiology, QR1-502
Abstract

ObjectivesTo evaluate the analytical and clinical performance of a prototype of a VIDAS® Galactomannan (GM) unitary test (bioMérieux, Marcy l’Etoile, France) and compare to that of the Platelia™ Aspergillus Ag assay (Bio-Rad, CA, USA).MethodsRepeatability, reproducibility, and freeze-thaw stability of VIDAS®GM were evaluated. Sera from patients at risk of IA were concurrently tested with both the VIDAS®GM and Platelia™ Aspergillus Ag assays. Correlations between the two assays were assessed by Passing Bablok (PB) regression and performance by ROC analysis.ResultsThe correlations between the VIDAS®GM indexes after one and two cycles of freezing/thawing were r=1.00 and r=0.989, respectively. The coefficients of variation for negative, low-positive, and positive sera were 13%, 6%, and 5% for repeatability and 14.4%, 7.2%, and 5.5% for reproducibility. Overall, 126 sera were tested with both assays (44 fresh and 82 frozen). The correlation between VIDAS®GM and Platelia™ Aspergillus Ag was r=0.798. The areas under the curve of the ROC analyses were 0.892 and 0.894, for VIDAS®GM and Platelia™ Aspergillus Ag, respectively.ConclusionsThis new VIDAS®GM prototype assay showed adequate analytical and clinical performance and a good correlation with that of Platelia™ Aspergillus Ag with 126 sera, although these results need to be confirmed in a larger prospective and multicentric study. As for the other VIDAS® assays, VIDAS®GM is a single-sample automated test using a solid reagent strip and receptacle. It is easy to use and suitable for rapid on-demand test results.

Published
2021
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8. Sporotrichosis in the Highlands of Madagascar, 2013–2017

Author

Tahinamandranto Rasamoelina, Danièle Maubon, Onivola Raharolahy, Harinjara Razanakoto, Njary Rakotozandrindrainy, Fetra Angelot Rakotomalala, Sébastien Bailly, Fandresena Sendrasoa, Irina Ranaivo, Malalaniaina Andrianarison, Benja Rakotonirina, Abel Andriantsimahavandy, Fahafahantsoa Rapelanoro Rabenja, Mala Rakoto Andrianarivelo, Lala Soavina Ramarozatovo, and Muriel Cornet

Subjects
Sporotrichosis, epidemiology, prevalence, molecular diagnosis, clinical presentation, outcome, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Sporotrichosis is a saprozoonotic fungal infection found mostly in tropical and subtropical areas. Few case reports in Madagascar have been published. To document sporotrichosis epidemiology in Madagascar, we conducted a cross-sectional study. During March 2013–June 2017, we recruited from select hospitals in Madagascar patients with chronic cutaneous lesions suggestive of dermatomycosis. Sporotrichosis was diagnosed for 63 (42.5%) of 148 patients. All but 1 patient came from the central highlands, where the prevalence was 0.21 cases/100,000 inhabitants. Frequency was high (64.7%) among patients

Published
2019
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9. Pythiosis: Case report leading to new features in clinical and diagnostic management of this fungal-like infection

Author

Diane Bernheim, Damien Dupont, Florent Aptel, Celine Dard, Christophe Chiquet, Anne Cécile Normand, Renaud Piarroux, Muriel Cornet, and Danièle Maubon

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

A 21-year-old man developed infectious keratitis after swimming in Spain whilst wearing contact lenses. Mycelial growth from a corneal sample suggested keratomycosis, but a drastic worsening of the patient’s condition was observed on antifungal drugs. On day 38, panfungal PCR identified Pythium insidiosum, which is an aquatic organism belonging to the oomycete family. Based on the recent literature, this patient was promptly prescribed a systemic and local antibiotic regimen and cure was ultimately achieved. In order to facilitate P. insidiosum identification in future cases, we have generated the first matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) reference spectrum for P. insidiosum. It is planned to deposit this MALDI-TOF MS reference spectrum on an open-access platform and this should allow immediate identification of the pathogen. Finally, this case report also demonstrates that P. insidiosum is emerging outside tropical and subtropical areas. Clinicians and microbiologists should have better knowledge to accurately manage and diagnose this sight-threatening infection. Keywords: Pythiosis, Pythium insidiosum, Keratitis, Panfungal PCR, MALDI-TOF mass spectrometry

Published
2019
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10. Molecular Diagnosis of Two Major Implantation Mycoses: Chromoblastomycosis and Sporotrichosis

Author

Danièle Maubon, Cécile Garnaud, Lala Soavina Ramarozatovo, Rapelanoro Rabenja Fahafahantsoa, Muriel Cornet, and Tahinamandranto Rasamoelina

Subjects
chromoblastomycosis, sporotrichosis, molecular, sequencing, PCR, MALDI-TOF MS, Biology (General), QH301-705.5
Abstract

Chromoblastomycosis and sporotrichosis are the two main implantation mycoses that are now recognized as fungal neglected tropical diseases (NTDs). Their laboratory diagnosis mainly relies on direct microscopy, histopathology, and identification of the fungus by culture. However, to be appropriately used, these techniques require mycological expertise that is not widely available and may be absent in peripheral health care facilities in endemic areas. In addition, they lack sensitivity and specificity, and the culture for isolation and identification can have a long time-to-results period. Molecular methods, including matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), have been developed in well-equipped reference laboratories. They greatly improve the rapidity and accuracy of diagnosis; in particular, for species identification. Recently, PCR and sequencing have paved the way for more user-friendly point-of-care tests, such as those based on LAMP or RCA technologies, which can be used in basic healthcare settings and even in field consultations.

Published
2022
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11. Evaluation of Microbiological Performance and the Potential Clinical Impact of the ePlex® Blood Culture Identification Panels for the Rapid Diagnosis of Bacteremia and Fungemia

Author

Sabrina Bryant, Iyad Almahmoud, Isabelle Pierre, Julie Bardet, Saber Touati, Daniele Maubon, Muriel Cornet, Claire Richarme, Max Maurin, Patricia Pavese, and Yvan Caspar

Subjects
sepsis, bacteremia, fungemia, early diagnosis, multiplex polymerase chain reaction, Microbiology, QR1-502
Abstract

Molecular rapid diagnostic assays associated with antimicrobial stewardship have proven effective for the early adaptation of empiric therapy in bloodstream infections. The ePlex® BCID (GenMark Diagnostics) Panels allow identification of 56 bacteria and fungi and 10 resistance genes in 90 min directly from positive blood cultures. We prospectively evaluated 187 sepsis episodes at Grenoble University Hospital and retrospectively analyzed the cases to measure the potential clinical impact of the ePlex BCID results. Identification of all pathogens was obtained for 164/187 (88%) bloodstream infections with 100% detection of antimicrobial resistance genes (17 blaCTX-M, 1 vanA, and 17 mecA genes). Only 15/209 (7%) strains were not covered by the panels. Sensitivity for detection of micro-organisms targeted by the RUO BCID-GP, BCID-GN, and BCID-FP Panels was respectively 84/84 (100%), 103/107 (96%), and 14/14 (100%). Interestingly, accurate identification of all pathogens was achieved in 15/17 (88%) polymicrobial samples. Retrospective analysis of medical records showed that a modification of antimicrobial treatment would have been done in 45% of the patients. Treatment modifications would have been an optimization of empiric therapy, a de-escalation or an escalation in respectively 16, 17, and 11% of the patients. Moreover, 11% of the samples were classified as contaminants or not clinically relevant and would have led to early de-escalation or withdrawal of any antibiotic. Detection of resistance genes in addition to identification alone increased escalation rate from 4 to 11% of the patients. Absence of the ePlex result was considered a lost opportunity for therapy modification in 28% of patients.

Published
2020
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12. Epidemiological characteristics of cryptococcal meningoencephalitis associated with Cryptococcus neoformans var. grubii from HIV-infected patients in Madagascar: A cross-sectional study.

Author

Rivonirina Andry Rakotoarivelo, Mihaja Raberahona, Tahinamandranto Rasamoelina, Andriamihaja Rabezanahary, Fetra Angelot Rakotomalala, Tiana Razafinambinintsoa, Thomas Bénet, Philippe Vanhems, Mamy Jean de Dieu Randria, Luisa Romanò, Massimo Cogliati, Muriel Cornet, and Mala Rakoto Andrianarivelo

Subjects
Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270
Abstract

Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts ≤200/μl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10-12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9-20.3) for cryptococcal infection and 10.9% (95% CI 6.1-17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p

Published
2020
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13. Added Value of Next-Generation Sequencing for Multilocus Sequence Typing Analysis of a Pneumocystis jirovecii Pneumonia Outbreak

Author

Elena Charpentier, Cécile Garnaud, Claire Wintenberger, Sébastien Bailly, Jean-Benjamin Murat, John Rendu, Patricia Pavese, Thibault Drouet, Caroline Augier, Paolo Malvezzi, Anne Thiébaut-Bertrand, Marie-Reine Mallaret, Olivier Epaulard, Muriel Cornet, Sylvie Larrat, and Danièle Maubon

Subjects
Pneumocystis jirovecii, pneumocystosis, pneumonia, disease outbreaks, infectious diseases, high-throughput nucleotide sequencing, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Pneumocystis jirovecii is a major threat for immunocompromised patients, and clusters of pneumocystis pneumonia (PCP) have been increasingly described in transplant units during the past decade. Exploring an outbreak transmission network requires complementary spatiotemporal and strain-typing approaches. We analyzed a PCP outbreak and demonstrated the added value of next-generation sequencing (NGS) for the multilocus sequence typing (MLST) study of P. jirovecii strains. Thirty-two PCP patients were included. Among the 12 solid organ transplant patients, 5 shared a major and unique genotype that was also found as a minor strain in a sixth patient. A transmission map analysis strengthened the suspicion of nosocomial acquisition of this strain for the 6 patients. NGS-MLST enables accurate determination of subpopulation, which allowed excluding other patients from the transmission network. NGS-MLST genotyping approach was essential to deciphering this outbreak. This innovative approach brings new insights for future epidemiologic studies on this uncultivable opportunistic fungus.

Published
2017
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14. Selective BET bromodomain inhibition as an antifungal therapeutic strategy

Author

Flore Mietton, Elena Ferri, Morgane Champleboux, Ninon Zala, Danièle Maubon, Yingsheng Zhou, Mike Harbut, Didier Spittler, Cécile Garnaud, Marie Courçon, Murielle Chauvel, Christophe d’Enfert, Boris A. Kashemirov, Mitchell Hull, Muriel Cornet, Charles E. McKenna, Jérôme Govin, and Carlo Petosa

Subjects
Science
Abstract

BET proteins bind chromatin through their bromodomains (BDs) to regulate transcription and chromatin remodelling. Here, the authors show that the BET protein Bdf1 is essential for the fungal pathogenCandida albicans, and report compounds that inhibit the Bdf1 BDs with high selectivity over human BDs.

Published
2017
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15. Dermatophyte infection caused by Nannizzia gypsea: A rare case report from Madagascar

Author

Abel Hermann Soankasina, Njariharinjakamampionona Rakotozandrindrainy, Solohery Andrianteloasy, Norosoa Julie Zafindraibe, Tahinamandranto Rasamoelina, Christian Rafalimanana, Muriel Cornet, Lala Rasoamialy Razanakolona, Andry Rasamindrakotroka, and Mala Rakoto Andrianarivelo

Subjects
Medicine (General), R5-920, Biology (General), QH301-705.5
Abstract

We report a rare case of dermatophyte infection of the glabrous skin (Tinea corporis) caused by Nannizzia gypsea (formerly Microsporum gypseum). A 22-year-old Malagasy female who reported close contact reportedly with cats, presented a single round lesion with a peripheral, active, squamous and pruriginous inflammatory bead. Morphologic species identification was confirmed by sequencing the internal transcribed spacer (ITS) region of the genome. Specific treatment with oral loratadine and topical miconazole cream was effective. Keywords: Nannizzia gypsea, Dermatophyte infection, ITS region, Madagascar

Published
2018
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16. MALDI-TOF MS in a Medical Mycology Laboratory: On Stage and Backstage

Author

Marie-Gladys Robert, Muriel Cornet, Aurélie Hennebique, Tahinamandranto Rasamoelina, Yvan Caspar, Léa Pondérand, Marie Bidart, Harmonie Durand, Marvin Jacquet, Cécile Garnaud, and Danièle Maubon

Subjects
MALDI-TOF MS, medical mycology, diagnosis, microorganism identification, fungi, antifungal susceptibility testing, Biology (General), QH301-705.5
Abstract

The implementation of MALDI-TOF MS in medical microbiology laboratories has revolutionized practices and significantly reduced turnaround times of identification processes. However, although bacteriology quickly benefited from the contributions of this technique, adjustments were necessary to accommodate the specific characteristics of fungi. MALDI-TOF MS is now an indispensable tool in clinical mycology laboratories, both for the identification of yeasts and filamentous fungi, and other innovative uses are gradually emerging. Based on the practical experience of our medical mycology laboratory, this review will present the current uses of MALDI-TOF MS and the adaptations we implemented, to allow their practical execution in a daily routine. We will also introduce some less mainstream applications, like those for fungemia, or even still under development, as is the case for the determination of sensitivity to antifungal agents or typing methods.

Published
2021
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17. Clinical Impact of Antifungal Susceptibility, Biofilm Formation and Mannoside Expression of Candida Yeasts on the Outcome of Invasive Candidiasis in ICU: An Ancillary Study on the Prospective AmarCAND2 Cohort

Author

Jean-Pierre Gangneux, Muriel Cornet, Sébastien Bailly, Chantal Fradin, Céline Féger, Jean-François Timsit, Olivier Leroy, Boualem Sendid, and Marie-Elisabeth Bougnoux

Subjects
invasive candidiasis, Candida albicans, Candida glabrata, virulence, biofilm, in vitro sensitivity, Microbiology, QR1-502
Abstract

Background: The link between Candida phenotypical characteristics and invasive candidiasis (IC) prognosis is still partially unknown.Methods:Candida strains isolated during the AmarCAND2 study were centrally analyzed for species identification, antifungal susceptibility, biofilm formation, and expression of surface and glycoconjugate mannosides. Correlation between these phenotypical features and patient outcome was sought using a multivariable Cox survival model.Results:Candida albicans was predominant (65.4%, n = 285), with a mortality rate significantly lower than that in patients with non-albicans strains [HR 0.67 (0.46–1.00), p = 0.048]. The rate of fluconazole-resistant strains was low (C. albicans and Candida glabrata: 3.5 and 6.2%, respectively) as well as caspofungin-resistant ones (1 and 3.1%, respectively). Early biofilm formation was less frequent among C. albicans (45.4%) than among non-albicans (81.2%). While the strains of C. albicans showed variable levels of surface mannosides expression, strains isolated from candidemia exhibited a high expression of β-man, which was correlated with an increased mortality (p = 0.02).Conclusion:Candida albicans IC were associated with lower mortality, and with strains that exhibited less frequently early biofilm formation than non-albicans strains. A high expression of β-man was associated with increased IC mortality. Further studies are warranted to confirm this data and to evaluate other virulence factors in yeasts.

Published
2018
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18. Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings

Author

David W. Denning, Iain D. Page, Jeremiah Chakaya, Kauser Jabeen, Cecilia M. Jude, Muriel Cornet, Ana Alastruey-Izquierdo, Felix Bongomin, Paul Bowyer, Arunaloke Chakrabarti, Sara Gago, John Guto, Bruno Hochhegger, Martin Hoenigl, Muhammad Irfan, Nicholas Irurhe, Koichi Izumikawa, Bruce Kirenga, Veronica Manduku, Samihah Moazam, Rita O. Oladele, Malcolm D. Richardson, Juan Luis Rodriguez Tudela, Anna Rozaliyani, Helmut J.F. Salzer, Richard Sawyer, Nasilele F. Simukulwa, Alena Skrahina, Charlotte Sriruttan, Findra Setianingrum, Bayu A.P. Wilopo, Donald C. Cole, and Haileyesus Getahun

Subjects
Tuberculosis, Aspergillus, antibody, aspergilloma, imaging, developing countries, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

Published
2018
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19. The Diagnosis of Fungal Neglected Tropical Diseases (Fungal NTDs) and the Role of Investigation and Laboratory Tests: An Expert Consensus Report

Author

Roderick Hay, David W Denning, Alexandro Bonifaz, Flavio Queiroz-Telles, Karlyn Beer, Beatriz Bustamante, Arunaloke Chakrabarti, Maria de Guadalupe Chavez-Lopez, Tom Chiller, Muriel Cornet, Roberto Estrada, Guadalupe Estrada-Chavez, Ahmed Fahal, Beatriz L Gomez, Ruoyu Li, Yesholata Mahabeer, Anisa Mosam, Lala Soavina Ramarozatovo, Mala Rakoto Andrianarivelo, Fahafahantsoa Rapelanoro Rabenja, Wendy van de Sande, and Eduard E Zijlstra

Subjects
fungal NTDs, laboratory diagnosis, mycetoma, sporotrichosis, chromoblastomycosis, integrated approaches, Medicine
Abstract

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs.

Published
2019
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20. Borrelia crocidurae Meningoencephalitis, West Africa

Author

Sandrine Goutier, Elisabeth Ferquel, Claudine Pinel, Annick Bosseray, Bruno Hoen, Gérard Couetdic, Amina Bourahoui, Claire Lapostolle, Hervé Pelloux, Martine Garnier, Natacha Sertour, Isabelle Pelloux, Patricia Pavese, and Muriel Cornet

Subjects
Borrelia crocidurae, meningitis, encephalitis, molecular diagnosis, West Africa, Borrelia meningitis, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

Borrelia crocidurae–associated relapsing fever is endemic to West Africa and is considered benign. We report 4 patients with B. crocidurae–associated neurologic symptoms; 2 of their cases had been misdiagnosed. Frequency and severity of this disease could be underestimated; molecular methods and serodiagnostic tests for Lyme disease might be helpful in its detection.

Published
2013
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21. Histone deacetylases and their inhibition in Candida species

Author

Cecile Garnaud, Morgane Champleboux, Daniele Maubon, Muriel Cornet, and Jerome Govin

Subjects
Acetylation, Candida, Chromatin, HDAC inhibitors, HDAC, Microbiology, QR1-502
Abstract

Fungi are generally benign members of the human mucosal flora or live as saprophytes in the environment. However, they can become pathogenic, leading to invasive and life threatening infections in vulnerable patients. These invasive fungal infections are regarded as a major public health problem on a similar scale to tuberculosis or malaria. Current treatment for these infections is based on only four available drug classes. This limited therapeutic arsenal and the emergence of drug-resistant strains are a matter of concern due to the growing number of patients to be treated, and new therapeutic strategies are urgently needed. Adaptation of fungi to drug pressure involves transcriptional regulation, in which chromatin dynamics and histone modifications play a major role. Histone deacetylases (HDACs) remove acetyl groups from histones and actively participate in controlling stress responses. HDAC inhibition has been shown to limit fungal development, virulence, biofilm formation and dissemination in the infected host, while also improving the efficacy of existing antifungal drugs towards Candida spp. In this article, we review the functional roles of HDACs and the biological effects of HDAC inhibitors on Candida spp., highlighting the correlations between their pathogenic effects in vitro and in vivo. We focus on how HDAC inhibitors could be used to treat invasive candidiasis while also reviewing recent developments in their clinical evaluation.

Published
2016
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22. Direct molecular diagnosis of aspergillosis and CYP51A profiling from respiratory samples of French patients

Author

Yanan Zhao, Cécile Garnaud, Marie-Pierre Brenier-Pinchart, Anne Thiébaut-Bertrand, Christel Saint-Raymond, Boubou Camara, Rebecca Hamidfar-Roy, Odile Cognet, Danièle Maubon, Muriel Cornet, and David S Perlin

Subjects
Aspergillus fumigatus, Molecular diagnostics, Azole resistance, Respiratory samples, CYP51A, French patients, Microbiology, QR1-502
Abstract

Background: Microbiological diagnosis of aspergillosis and triazole resistance is limited by poor culture yield. To better estimate this shortcoming, we compared culture and molecular detection of A. fumigatus in respiratory samples from French patients at risk for aspergillosis. Methods: A total of 97 respiratory samples including bronchoalveolar lavages (BAL), bronchial aspirates (BA), tracheal aspirates, sputa, pleural fluids, and lung biopsy were collected from 33 patients having invasive aspergillosis (n=12), chronic pulmonary aspergillosis (n=3), allergic bronchopulmonary aspergillosis (n=7) or colonization (n=11) and 28 controls. Each specimen was evaluated by culture, pan-Aspergillus qPCR, and CYP51A PCR and sequencing. Results: One A. flavus and 19 A. fumigatus with one multiazole resistant strain (5.3%) were cultured from 20 samples. Culture positivity was 62.5%, 75%, 42.9%, and 15.8% in ABPA, CPA, IA and colonized patients, respectively. Aspergillus detection rate was significantly higher by pan-Aspergillus qPCR than by culture in IA (90.5% vs 42.9%; P

Published
2016
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23. Rapid Fatal Outcome of Cryptococcal Meningoencephalitis in a Non-HIV Immunocompromised Patient with a Low Fluconazole Susceptibility Isolate: A Case Report from Madagascar

Author

Mihaja Raberahona, Rivonirina A. Rakotoarivelo, Njary Randriamampionona, Angelot F. Rakotomalala, Tiana Razafinambinintsoa, Thomas Bénet, Philippe Vanhems, Mamy J. D. D. Randria, Muriel Cornet, and Mala Rakoto-Andrianarivelo

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Cryptococcal meningoencephalitis is considered rare in HIV-negative individuals. In Madagascar, the epidemiology of cryptococcosis has not yet been well described, neither in immunocompetent nor in immunocompromised patients. We report here the first Malagasy detailed case of cryptococcal meningoencephalitis in a non-HIV immunocompromised adult patient carrying a low fluconazole susceptibility isolate. We emphasize the importance of early and accurate diagnosis to meet the challenges of managing cryptococcosis in developing countries.

Published
2016
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24. Severe Leptospirosis in Hospitalized Patients, Guadeloupe

Author

Cécile Herrmann-Storck, Magalie Saint Louis, Tania Foucand, Isabelle Lamaury, Jacqueline Deloumeaux, Guy Baranton, Maurice Simonetti, Natacha Sertour, Muriel Nicolas, Jacques Salin, and Muriel Cornet

Subjects
Leptospirosis, prognostic factors, serovar, virulence, reservoir hosts, Guadeloupe, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We evaluated prognostic factors for leptospirosis in 168 consecutive hospitalized patients in Guadeloupe. Factors independently associated with severity included chronic hypertension or chronic alcoholism, late initiation of antibacterial therapy, abnormal chest auscultation results, icterus, oligoanuria, disorders of consciousness, elevated aspartate aminotransferase levels, hyperamylasemia, and Leptospira interrogans serovar Icterohemorrhagiae.

Published
2010
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25. Borrelia hispanica Relapsing Fever, Morocco

Author

M’hammed Sarih, Martine Garnier, Najma Boudebouch, Ali Bouattour, Abdelaziz Rihani, Mohammed Hassar, Lise Gern, Danièle Postic, and Muriel Cornet

Subjects
Relapsing fever, Borrelia hispanica, molecular diagnosis, bacteria, vector-borne infections, Morocco, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We found that 20.5% of patients with an unexplained fever in northwestern Morocco had tick-borne relapsing fever. Molecular detection specific for the 16S rRNA gene identified Borrelia hispanica. The noncoding intergenic spacer sequence domain showed high sensitivity and good resolution for this species.

Published
2009
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27. First isolation and direct evidence for the existence of large small-mammal reservoirs of Leptospira sp. in Madagascar.

Author

Soanandrasana Rahelinirina, Albertine Léon, Rudy A Harstskeerl, Natacha Sertour, Ahmed Ahmed, Claudine Raharimanana, Elisabeth Ferquel, Martine Garnier, Loïc Chartier, Jean-Marc Duplantier, Lila Rahalison, and Muriel Cornet

Subjects
Medicine, Science
Abstract

BACKGROUND: Leptospirosis has long been a major public health concern in the southwestern Indian Ocean. However, in Madagascar, only a few, old studies have provided indirect serological evidence of the disease in humans or animals. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a large animal study focusing on small-mammal populations. Five field trapping surveys were carried out at five sites, from April 2008 to August 2009. Captures consisted of Rattus norvegicus (35.8%), R. rattus (35.1%), Mus musculus (20.5%) and Suncus murinus (8.6%). We used microbiological culture, serodiagnosis tests (MAT) and real-time PCR to assess Leptospira infection. Leptospira carriage was detected by PCR in 91 (33.9%) of the 268 small mammals, by MAT in 17 of the 151 (11.3%) animals for which serum samples were available and by culture in 9 of the 268 animals (3.3%). Rates of infection based on positive PCR results were significantly higher in Moramanga (54%), Toliara (48%) and Mahajanga (47.4%) than in Antsiranana (8.5%) and Toamasina (14%) (p = 0.001). The prevalence of Leptospira carriage was significantly higher in R. norvegicus (48.9%), S. murinus (43.5%) and R. rattus (30.8%) than in M. musculus (9.1%) (p

Published
2010
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28. Clinical aspects of previously treated chromoblastomycosis: A case series from Madagascar

Author

Lala Soavina Ramarozatovo, M.F. Rakotoarisaona, Irina Mamisoa Ranaivo, Muriel Cornet, Mala Rakoto Andrianarivelo, N.H. Razanakoto, M. Andrianarison, Danièle Maubon, Fahafahantsoa Rapelanoro Rabenja, Volatantely Ratovonjanahary, Moril Sata, O. Raharolahy, Fandresena Arilala Sendrasoa, and Tahinamandranto Rasamoelina

Subjects
Adult, Male, 0301 basic medicine, Microbiology (medical), Antifungal, medicine.medical_specialty, Antifungal Agents, medicine.drug_class, Itraconazole, 030106 microbiology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Cicatricial lesion, medicine, Madagascar, Humans, lcsh:RC109-216, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Terbinafine, Aged, Chromoblastomycosis, business.industry, General Medicine, Middle Aged, University hospital, medicine.disease, Dermatology, Infectious Diseases, Female, Previously treated, business, Fluconazole, medicine.drug
Abstract

Objective To describe the clinical aspects of chromoblastomycosis (CBM) presented by patients who had received incomplete antifungal treatment before consultation. Methods A prospective study of patients with clinically suspected CBM was performed between 2013 and 2018 in the Department of Dermatology at the University Hospital Antananarivo, and during consultation campaigns. Results Patients develop CBM over a period of more than 10 years, and many will have already received antifungals prescribed by general practitioners before consulting with a dermatologist. Such treatment obviously modifies the clinical presentation. From the 63 CBM patients in this large study, we describe 12 patients who received oral antifungals (terbinafine, griseofulvine, itraconazole, fluconazole) before consultation. The most frequent clinical aspect presented by these patients was cicatricial lesions, which are characteristically smooth and non-elevated, and enlarge by peripheral extension, with atrophic scarring at the center. Conclusion Our study is the first to show that cicatricial lesions are a clinical aspect presented by CBM patients who received antifungals before presentation.

Published
2020

29. Endemic Chromoblastomycosis Caused Predominantly by Fonsecaea nubica, Madagascar1

Author

Njary Rakotozandrindrainy, Abel Andriantsimahavandy, Lala Soavina Ramarozatovo, Benja Rakotonirina, Fahafahantsoa Rakato Rabenja, Mala Rakoto Andrianarivelo, Fandresena Arilala Sendrasoa, Fetra Angelot Rakotomalala, Tahinamandranto Rasamoelina, Sébastien Bailly, Irina Mamisoa Ranaivo, M. Andrianarison, Muriel Cornet, and Danièle Maubon

Subjects
Microbiology (medical), medicine.medical_specialty, Fonsecaea, Chromoblastomycosis, biology, Epidemiology, business.industry, 030231 tropical medicine, Dermatomycosis, biology.organism_classification, medicine.disease, Dermatology, Molecular analysis, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Fonsecaea nubica, Medicine, 030212 general & internal medicine, business, Cladophialophora carrionii
Abstract

Chromoblastomycosis is an implantation fungal infection. Twenty years ago, Madagascar was recognized as the leading focus of this disease. We recruited patients in Madagascar who had chronic subcutaneous lesions suggestive of dermatomycosis during March 2013-June 2017. Chromoblastomycosis was diagnosed in 50 (33.8%) of 148 patients. The highest prevalence was in northeastern (1.47 cases/100,000 persons) and southern (0.8 cases/100,000 persons) Madagascar. Patients with chromoblastomycosis were older (47.9 years) than those without (37.5 years) (p = 0.0005). Chromoblastomycosis was 3 times more likely to consist of leg lesions (p = 0.003). Molecular analysis identified Fonsecaea nubica in 23 cases and Cladophialophora carrionii in 7 cases. Of 27 patients who underwent follow-up testing, none were completely cured. We highlight the persistence of a high level of chromoblastomycosis endemicity, which was even greater at some locations than 20 years ago. We used molecular tools to identify the Fonsecaea sp. strains isolated from patients as F. nubica.

Published
2020
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30. Fungal infections in mechanically ventilated patients with COVID-19 during the first wave: the French multicentre MYCOVID study

Author

Gilles Nevez, Brice Autier, Jean-Pierre Gangneux, Yves Cohen, Nadine François, Cécile Aubron, Emmanuel Canet, Sophie Brun, Alexandre Alanio, Philippe Seguin, Nicolas Terzi, Bruno Mégarbane, Jean-François Timsit, Romain Pelletier, Marie Soulié, Dorothée Quinio, Estelle Sabourin, Nicolas de Prost, Juliette Guitard, Frederique Boquel, Valérie Letscher-Bru, Jeff Morcet, Stephan Ehrmann, Guillaume Voiriot, Solène Le Gal, Florent Morio, Bruno Laviolle, Jean-Christophe Richard, Laurent Argaud, Estelle Cateau, Marion Blaize, Matthieu Lesouhaitier, Patrice Le Pape, Carole Schwebel, Florent Wallet, Jordan Leroy, Jean-Ralph Zahar, Ana Novara, Hélène Guegan, Béatrice Riu-Poulenc, Florence Robert-Gangneux, Jean Menotti, Eric Dannaoui, Sorya Belaz, Yves Le Tulzo, Muriel Cornet, Saad Nseir, Ferhat Meziani, Damien Dupont, Boualem Sendid, Antoine Monsel, Florian Reizine, Xavier Iriart, Francoise Botterel, Arnaud Fekkar, Charles-Edouard Luyt, Cécile Garnaud, Melek Manai, Lionel Lamhaut, Jean-Marc Tadié, Julien Mayaux, Sylvie Paulus, Florence Persat, Marie-Elisabeth Bougnoux, Christophe Hennequin, Christine Bonnal, Arnaud W. Thille, Antoine Berry, Sandrine Houze, Guillaume Desoubeaux, Centre Hospitalier Universitaire [Rennes], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Lille, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital Avicenne [AP-HP], Hôpitaux Universitaire Saint-Louis, Lariboisière, Fernand-Widal, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Necker - Enfants Malades [AP-HP], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 (CEPR), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Strasbourg, and CarMeN, laboratoire

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, Multivariate analysis, Coronavirus disease 2019 (COVID-19), medicine.medical_treatment, [SDV]Life Sciences [q-bio], Population, Intensive care, Internal medicine, medicine, Humans, education, Mechanical ventilation, education.field_of_study, Coinfection, SARS-CoV-2, business.industry, Mucormycosis, COVID-19, Articles, Odds ratio, medicine.disease, [SDV] Life Sciences [q-bio], Mycoses, business, Cohort study
Abstract

International audience; BACKGROUND: Patients with severe COVID-19 have emerged as a population at high risk of invasive fungal infections (IFIs). However, to our knowledge, the prevalence of IFIs has not yet been assessed in large populations of mechanically ventilated patients. We aimed to identify the prevalence, risk factors, and mortality associated with IFIs in mechanically ventilated patients with COVID-19 under intensive care. METHODS: We performed a national, multicentre, observational cohort study in 18 French intensive care units (ICUs). We retrospectively and prospectively enrolled adult patients (aged ≥18 years) with RT-PCR-confirmed SARS-CoV-2 infection and requiring mechanical ventilation for acute respiratory distress syndrome, with all demographic and clinical and biological follow-up data anonymised and collected from electronic case report forms. Patients were systematically screened for respiratory fungal microorganisms once or twice a week during the period of mechanical ventilation up to ICU discharge. The primary outcome was the prevalence of IFIs in all eligible participants with a minimum of three microbiological samples screened during ICU admission, with proven or probable (pr/pb) COVID-19-associated pulmonary aspergillosis (CAPA) classified according to the recent ECMM/ISHAM definitions. Secondary outcomes were risk factors of pr/pb CAPA, ICU mortality between the pr/pb CAPA and non-pr/pb CAPA groups, and associations of pr/pb CAPA and related variables with ICU mortality, identified by regression models. The MYCOVID study is registered with ClinicalTrials.gov, NCT04368221. FINDINGS: Between Feb 29 and July 9, 2020, we enrolled 565 mechanically ventilated patients with COVID-19. 509 patients with at least three screening samples were analysed (mean age 59·4 years [SD 12·5], 400 [79%] men). 128 (25%) patients had 138 episodes of pr/pb or possible IFIs. 76 (15%) patients fulfilled the criteria for pr/pb CAPA. According to multivariate analysis, age older than 62 years (odds ratio [OR] 2·34 [95% CI 1·39-3·92], p=0·0013), treatment with dexamethasone and anti-IL-6 (OR 2·71 [1·12-6·56], p=0·027), and long duration of mechanical ventilation (\textgreater14 days; OR 2·16 [1·14-4·09], p=0·019) were independently associated with pr/pb CAPA. 38 (7%) patients had one or more other pr/pb IFIs: 32 (6%) had candidaemia, six (1%) had invasive mucormycosis, and one (\textless1%) had invasive fusariosis. Multivariate analysis of associations with death, adjusted for candidaemia, for the 509 patients identified three significant factors: age older than 62 years (hazard ratio [HR] 1·71 [95% CI 1·26-2·32], p=0·0005), solid organ transplantation (HR 2·46 [1·53-3·95], p=0·0002), and pr/pb CAPA (HR 1·45 [95% CI 1·03-2·03], p=0·033). At time of ICU discharge, survival curves showed that overall ICU mortality was significantly higher in patients with pr/pb CAPA than in those without, at 61·8% (95% CI 50·0-72·8) versus 32·1% (27·7-36·7; p\textless0·0001). INTERPRETATION: This study shows the high prevalence of invasive pulmonary aspergillosis and candidaemia and high mortality associated with pr/pb CAPA in mechanically ventilated patients with COVID-19. These findings highlight the need for active surveillance of fungal pathogens in patients with severe COVID-19. FUNDING: Pfizer.

Published
2022
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31. Pythiosis: Case report leading to new features in clinical and diagnostic management of this fungal-like infection

Author

Anne Cécile Normand, Diane Bernheim, Danièle Maubon, Renaud Piarroux, Damien Dupont, Muriel Cornet, Christophe Chiquet, Céline Dard, Florent Aptel, CHU Grenoble, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Antibiotic regimen, Antifungal drugs, [SDV]Life Sciences [q-bio], 030106 microbiology, Infectious Keratitis, Pythium insidiosum, Aquatic organisms, Keratitis, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Pythiosis, 0302 clinical medicine, Medicine, lcsh:RC109-216, 030212 general & internal medicine, biology, business.industry, General Medicine, MALDI-TOF Mass Spectrometry, medicine.disease, biology.organism_classification, Dermatology, 3. Good health, Infectious Diseases, business
Abstract

A 21-year-old man developed infectious keratitis after swimming in Spain whilst wearing contact lenses. Mycelial growth from a corneal sample suggested keratomycosis, but a drastic worsening of the patient’s condition was observed on antifungal drugs. On day 38, panfungal PCR identified Pythium insidiosum, which is an aquatic organism belonging to the oomycete family. Based on the recent literature, this patient was promptly prescribed a systemic and local antibiotic regimen and cure was ultimately achieved. In order to facilitate P. insidiosum identification in future cases, we have generated the first matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) reference spectrum for P. insidiosum. It is planned to deposit this MALDI-TOF MS reference spectrum on an open-access platform and this should allow immediate identification of the pathogen. Finally, this case report also demonstrates that P. insidiosum is emerging outside tropical and subtropical areas. Clinicians and microbiologists should have better knowledge to accurately manage and diagnose this sight-threatening infection. Keywords: Pythiosis, Pythium insidiosum, Keratitis, Panfungal PCR, MALDI-TOF mass spectrometry

Published
2019
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32. Sporotrichosis in the Highlands of Madagascar, 2013–20171

Author

Danièle Maubon, Fandresena Arilala Sendrasoa, Njary Rakotozandrindrainy, O. Raharolahy, Tahinamandranto Rasamoelina, Fetra Angelot Rakotomalala, Benja Rakotonirina, Harinjara Razanakoto, Lala Soavina Ramarozatovo, Abel Andriantsimahavandy, Sébastien Bailly, Mala Rakoto Andrianarivelo, Fahafahantsoa Rapelanoro Rabenja, Irina Mamisoa Ranaivo, M. Andrianarison, and Muriel Cornet

Subjects
Male, Antifungal Agents, Cross-sectional study, clinical presentation, highlands, Dermatomycosis, Polymerase Chain Reaction, 0302 clinical medicine, Epidemiology, Sporothrix schenckii, 030212 general & internal medicine, Child, Aged, 80 and over, biology, Age Factors, Middle Aged, Sporotrichosis in the Highlands of Madagascar, 2013–2017, Infectious Diseases, Child, Preschool, outcome, epidemiology, Female, Itraconazole, geographic locations, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, prevalence, 03 medical and health sciences, Young Adult, parasitic diseases, molecular diagnosis, medicine, Madagascar, Humans, Central Highlands, Aged, Sporotrichosis, business.industry, Research, Sporothrix, biology.organism_classification, medicine.disease, Dermatology, zoonoses, Cross-Sectional Studies, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, fungi, business
Abstract

Sporotrichosis is a saprozoonotic fungal infection found mostly in tropical and subtropical areas. Few case reports in Madagascar have been published. To document sporotrichosis epidemiology in Madagascar, we conducted a cross-sectional study. During March 2013-June 2017, we recruited from select hospitals in Madagascar patients with chronic cutaneous lesions suggestive of dermatomycosis. Sporotrichosis was diagnosed for 63 (42.5%) of 148 patients. All but 1 patient came from the central highlands, where the prevalence was 0.21 cases/100,000 inhabitants. Frequency was high (64.7%) among patients

Published
2019

33. MALDI-TOF MS in a Medical Mycology Laboratory: On Stage and Backstage

Author

Yvan Caspar, Danièle Maubon, Muriel Cornet, Cécile Garnaud, Marvin Jacquet, Léa Pondérand, Tahinamandranto Rasamoelina, Marie Bidart, Aurélie Hennebique, Marie-Gladys Robert, Harmonie Durand, Centre Hospitalier Universitaire [Grenoble] (CHU), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Groupe Pathogenèse Bactérienne et Réponses Cellulaires / Bacterial Pathogenesis and Cellular Responses Group (IBS-PBRC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), 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), Translational microbial Evolution and Engineering (TIMC-TrEE), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Centre d’Infectiologie Charles-Mérieux, Université d’Antananarivo - Madagascar, Université d'Antananarivo, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)

Subjects
0301 basic medicine, Microbiology (medical), Antifungal, medicine.medical_specialty, Medical mycology, medicine.drug_class, Computer science, QH301-705.5, diagnosis, [SDV]Life Sciences [q-bio], 030106 microbiology, Review, Microbiology, 03 medical and health sciences, Virology, medicine, MALDI-TOF MS, Medical physics, Biology (General), Daily routine, Fungemia, antifungal susceptibility testing, medicine.disease, 3. Good health, 030104 developmental biology, microorganism identification, Typing methods, fungi, medical mycology
Abstract

International audience; The implementation of MALDI-TOF MS in medical microbiology laboratories has revolutionized practices and significantly reduced turnaround times of identification processes. However, although bacteriology quickly benefited from the contributions of this technique, adjustments were necessary to accommodate the specific characteristics of fungi. MALDI-TOF MS is now an indispensable tool in clinical mycology laboratories, both for the identification of yeasts and filamentous fungi, and other innovative uses are gradually emerging. Based on the practical experience of our medical mycology laboratory, this review will present the current uses of MALDI-TOF MS and the adaptations we implemented, to allow their practical execution in a daily routine. We will also introduce some less mainstream applications, like those for fungemia, or even still under development, as is the case for the determination of sensitivity to antifungal agents or typing methods.

Published
2021
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34. Evaluation of Microbiological Performance and the Potential Clinical Impact of the ePlex® Blood Culture Identification Panels for the Rapid Diagnosis of Bacteremia and Fungemia

Author

Isabelle Pierre, Sabrina Bryant, Iyad Almahmoud, Muriel Cornet, Yvan Caspar, Claire Richarme, Saber Touati, Danièle Maubon, Julie Bardet, Max Maurin, and Patricia Pavese

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, medicine.drug_class, 030106 microbiology, Immunology, Antibiotics, lcsh:QR1-502, Microbiology, lcsh:Microbiology, sepsis, Sepsis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Antimicrobial stewardship, Blood culture, 030212 general & internal medicine, bacteremia, Fungemia, fungemia, medicine.diagnostic_test, business.industry, medicine.disease, Antimicrobial, Infectious Diseases, Bacteremia, business, multiplex polymerase chain reaction, Empiric therapy, early diagnosis
Abstract

Molecular rapid diagnostic assays associated with antimicrobial stewardship have proven effective for the early adaptation of empiric therapy in bloodstream infections. The ePlex® BCID (GenMark Diagnostics) Panels allow identification of 56 bacteria and fungi and 10 resistance genes in 90 min directly from positive blood cultures. We prospectively evaluated 187 sepsis episodes at Grenoble University Hospital and retrospectively analyzed the cases to measure the potential clinical impact of the ePlex BCID results. Identification of all pathogens was obtained for 164/187 (88%) bloodstream infections with 100% detection of antimicrobial resistance genes (17 blaCTX-M, 1 vanA, and 17 mecA genes). Only 15/209 (7%) strains were not covered by the panels. Sensitivity for detection of micro-organisms targeted by the RUO BCID-GP, BCID-GN, and BCID-FP Panels was respectively 84/84 (100%), 103/107 (96%), and 14/14 (100%). Interestingly, accurate identification of all pathogens was achieved in 15/17 (88%) polymicrobial samples. Retrospective analysis of medical records showed that a modification of antimicrobial treatment would have been done in 45% of the patients. Treatment modifications would have been an optimization of empiric therapy, a de-escalation or an escalation in respectively 16, 17, and 11% of the patients. Moreover, 11% of the samples were classified as contaminants or not clinically relevant and would have led to early de-escalation or withdrawal of any antibiotic. Detection of resistance genes in addition to identification alone increased escalation rate from 4 to 11% of the patients. Absence of the ePlex result was considered a lost opportunity for therapy modification in 28% of patients.

Published
2020
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35. Mucormycosis in intensive care unit: surgery is a major prognostic factor in patients with hematological malignancy

Author

Romaric Larcher, Damien Contou, Johanna Claustre, Jean-Michel Constantin, Laurent Argaud, Alexandre Lautrette, Juliette Pocquet, Yoann Zerbib, Rémi Coudroy, Pierre Lavagne, Jean-Christophe Navellou, Guillaume Voiriot, Pierre-Emmanuel Charles, Jean Dellamonica, Thomas Jouve, Michel Durand, Pierre Phelouzat, Muriel Cornet, Saad Nseir, Cédric Daubin, Julien Cadiet, Carole Schwebel, Anne-Sophie Truche, Nicolas Terzi, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Service de soins intensifs, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réanimation Médicale, CHU Lille, Lille, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Picardie Jules Verne (UPJV), Unité de soins intensifs [Clermont Ferrand], CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Soins Intensifs [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Médecine Intensive et Réanimation [Lyon], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Pontchaillou [Rennes], Service de réanimation médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de réanimation médicale et infectieuse, 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), Réanimation Médicale CHRU Besançon, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Réanimation Médicale [Grenoble], CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire [Grenoble] (CHU), Médecine Intensive et Réanimation [Grenoble], CHU Grenoble, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Lille, CNRS, Centre de Recherche en Transplantation et Immunologie [U1064 Inserm - CRTI], CHU Montpellier, Centre Hospitalier Universitaire [Grenoble] [CHU], Service de néphrologie, dialyse, aphérèses et transplantation, Unité de Glycobiologie Structurale et Fonctionnelle (UGSF) - UMR 8576, Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Centre hospitalier universitaire de Nantes [CHU Nantes], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand [CHU Dijon], Service de réanimation médicale [CHU Caen], Centre hospitalier universitaire de Poitiers [CHU Poitiers], CHU Nice [Cimiez], CIC CHU Lyon (inserm), Service de réanimation cardio-vasculaire et thoracique, Laboratoire de parasitologie-mycologie, and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, [SDV]Life Sciences [q-bio], Prognostic factors, Critical Care and Intensive Care Medicine, law.invention, 03 medical and health sciences, 0302 clinical medicine, Hematological malignancy, law, Intensive care, Anesthesiology, Diabetes mellitus, Internal medicine, Epidemiology, medicine, Mucormycosis, Intensive care unit, 030212 general & internal medicine, Survival rate, 2. Zero hunger, 0303 health sciences, 030306 microbiology, business.industry, Research, Incidence (epidemiology), Surgery, lcsh:Medical emergencies. Critical care. Intensive care. First aid, lcsh:RC86-88.9, medicine.disease, 3. Good health, business
Abstract

Background Mucormycosis is an invasive fungal infection, with an increasing incidence especially in patients with hematological malignancies. Its prognosis is poor because of its high invasive power and its intrinsic low susceptibility to antifungal agents. We aimed to describe the epidemiology of mucormycosis in intensive care units (ICU) and evaluate the outcomes. We performed a retrospective multi-center study in 16 French ICUs between 2008 and 2017. We compared the patients who survived in ICU and the patients who did not to identify factors associated with ICU survival. Then, we focused on the subgroup of patients with hematological malignancies. Results Mucormycosis was diagnosed in 74 patients during the study period. Among them, 60 patients (81%) were immunocompromised: 41 had hematological malignancies, 9 were solid organ transplant recipients, 31 received long-term steroids, 11 had diabetes, 24 had malnutrition. Only 21 patients survived to ICU stay (28.4%) with a median survival of 22 days (Q1–Q3 = 9–106) and a survival rate at day 28 and day 90, respectively, of 35.1% and 26.4%. Survivors were significantly younger (p = 0.001), with less frequently hematological malignancies (p = 0.02), and less malnutrition (p = 0.05). Median survival in patients with hematological malignancies (n = 41) was 15 days (Q1–Q3 = 5–23.5 days). In this subgroup, curative surgery was a major factor associated with survival in multivariate analysis (odds ratio = 0.71, [0.45–0.97], p Conclusion Overall prognosis of mucormycosis in ICU remains poor, especially in patients with hematological malignancies. In this subgroup of patients, a therapeutic strategy including curative surgery was the main factor associated with survival.

Published
2020
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36. Evaluation of ID Fungi Plates Medium for Identification of Molds by MALDI Biotyper

Author

Danièle Maubon, Thomas Girard, Céline Dard, Tahinamandranto Rasamoelina, Odile Cognet, Muriel Cornet, Charlotte Romero, Marie Gladys Robert, and Cécile Garnaud

Subjects
Microbiology (medical), Antifungal, food.ingredient, Hypha, Diagnostic Tests, Routine, medicine.drug_class, Extraction (chemistry), Fungi, Mycology, Direct transfer, Biology, Culture Media, food, Ascomycota, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, medicine, Humans, Agar, Food science, Subculture (biology), Microscopic morphology, Candida, Fungal material
Abstract

MALDI-TOF mass spectrometry (MS) identification of pathogenic filamentous fungi is often impaired by difficulties in harvesting hyphae embedded in the medium and long extraction protocols. The ID Fungi Plate (IDFP) is a novel culture method developed to address such difficulties and improve the identification of filamentous fungi by MALDI-TOF MS. We cultured 64 strains and 11 clinical samples on IDFP, Sabouraud agar-chloramphenicol (SAB), and ChromID Candida agar (CAN2). We then compared the three media for growth, ease of harvest, amount of material picked, and MALDI-TOF identification scores after either rapid direct transfer (DT) or a long ethanol-acetonitrile (EA) extraction protocol. Antifungal susceptibility testing and microscopic morphology after subculture on SAB and IDFP were also compared for ten molds. Growth rates and morphological aspects were similar for the three media. With IDFP, harvesting of fungal material for the extraction procedure was rapid and easy in 92.4% of cases, whereas it was tedious on SAB or CAN2 in 65.2% and 80.3% of cases, respectively. The proportion of scores above 1.7 (defined as acceptable identification) were comparable for both extraction protocols using IDFP (P = 0.256). Moreover, rates of acceptable identification after DT performed on IDFP (93.9%) were significantly higher than those obtained after EA extraction with SAB (69.7%) or CAN2 (71.2%) (P =

Published
2020
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37. Epidemiological characteristics of cryptococcal meningoencephalitis associated with Cryptococcus neoformans var. grubii from HIV-infected patients in Madagascar: A cross-sectional study

Author

Mihaja Raberahona, Andriamihaja Rabezanahary, Rivonirina Andry Rakotoarivelo, Luisa Romanò, Tiana Razafinambinintsoa, Mamy Jean de Dieu Randria, Thomas Bénet, Tahinamandranto Rasamoelina, Massimo Cogliati, Fetra Angelot Rakotomalala, Philippe Vanhems, Mala Rakoto Andrianarivelo, Muriel Cornet, Université de Fianarantsoa, Hôpital Joseph Raseta Befelatanana, CHU d’Antananarivo, Université d'Antananarivo, Centre Hospitalier Universitaire Analakininina [Toamasina, Madagascar], Service d'Hygiène, Epidémiologie et Prévention [Hôpital Edouard Herriot - HCL], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire des pathogènes émergents -- Emerging Pathogens Laboratory (LPE-Fondation Mérieux), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano [Milano] (UNIMI), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), This work was funded by grants from the European & Developing Countries Clinical Trials Partnership EDCTP (MF.2013.40205.018) and Fondation Mérieux, Lyon., Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Milano = University of Milan (UNIMI), Bodescot, Myriam, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, RNA viruses, 0301 basic medicine, Physiology, RC955-962, Cryptococcus, HIV Infections, Meningitis, Cryptococcal, Pathology and Laboratory Medicine, Nervous System, Flucytosine, Geographical Locations, 0302 clinical medicine, Immunodeficiency Viruses, Infectious Diseases of the Nervous System, Meningoencephalitis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Amphotericin B, Arctic medicine. Tropical medicine, Medicine and Health Sciences, Amphotericin, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Cerebrospinal Fluid, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Fungal Pathogens, biology, Antimicrobials, Eukaryota, Drugs, Middle Aged, Body Fluids, 3. Good health, Infectious Diseases, Neurology, Medical Microbiology, Viral Pathogens, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Pathogens, Anatomy, Public aspects of medicine, RA1-1270, Research Article, medicine.drug, Adult, medicine.medical_specialty, Cryptococcus Neoformans, 030231 tropical medicine, Mycology, Opportunistic Infections, Microbiology, 03 medical and health sciences, Microbial Control, Internal medicine, Retroviruses, Madagascar, medicine, Humans, Microbial Pathogens, Pharmacology, Cryptococcus neoformans, Voriconazole, Antifungals, business.industry, Lentivirus, Organisms, Fungi, Public Health, Environmental and Occupational Health, Biology and Life Sciences, HIV, biology.organism_classification, medicine.disease, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Cross-Sectional Studies, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, People and Places, Africa, Cryptococcosis, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Fluconazole
Abstract

Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide. The main objective of this study was to describe the prevalence of CM and cryptococcal infection in HIV-infected patients in Madagascar. The secondary objectives were to assess the adjusted prevalence of CM according to clinical presentation and patient characteristics, to determine crude 90-day survival according to cryptococcal antigen (CrAg) status and CM, and to identify the genotypes of Cryptococcus clinical isolates. This cross-sectional study was carried out at two urban hospitals in Antananarivo (central highlands) and Toamasina (east coast) between November 2014 and December 2016. Consecutive HIV-infected adults presenting with CD4 cell counts ≤200/μl were enrolled. Lateral flow immunoassays of CrAg were performed on serum for all patients, and on cerebrospinal fluid for patients with CM symptoms. MALDI-ToF MS, ITS sequencing, and determinations of the molecular and mating types of the isolates were performed. Fluconazole is the only drug for CM treatment available in Madagascar. Patients were treated orally, with high doses (1200 mg/day) for 10–12 weeks and then with 200 mg/day. Minimum inhibitory concentrations were determined for amphotericin B, flucytosine, voriconazole and fluconazole in E-tests. Overall prevalence was 13.2% (95% CI 7.9–20.3) for cryptococcal infection and 10.9% (95% CI 6.1–17.5) for CM, among the 129 HIV-infected patients studied. The 90-day mortality rate was 58.8% (10/17) in CrAg-positive patients and 17.9% (20/112) in CrAg-negative patients (p, Author summary Cryptococcal meningoencephalitis (CM) remains the most prevalent invasive fungal infection worldwide, with an estimated mortality of 70% in sub-Saharan Africa. In this cross-sectional study, we investigated the prevalence, clinical features, case-management and outcome of CM in HIV-infected patients. We also molecularly characterized the Cryptococcus isolates from these patients. The study was conducted in the main hospitals of two geographically distant cities, one located at Antananarivo in the central highlands and the other at Toamasina on the east coast. The prevalence of cryptococcal infection was higher than previously reported global prevalence values, and most of the patients developed CM. Classical signs of meningoencephalitis, including headache, fever and neck pain, were observed, as reported in previous studies. Ninety-day mortality (58.8%) was higher in patients with Cryptococcus infections than in non-infected patients (17.9%). All patients diagnosed with infection were treated with high-dose fluconazole, the only treatment available in Madagascar, in accordance with WHO recommendations. Molecular analyses of isolates from both regions revealed high levels of genome diversity and suggested that further environmental and larger clinical studies would be worthwhile. In conclusion, the prevalence of cryptococcal diseases is high in Madagascar, which is currently faced with the challenges of prioritizing various diseases of public health concern, providing health centers with rapid diagnostic tools and facilitating access to more reliable molecules.

Published
2020
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38. Profile of GenMark’s ePlex® blood culture identification fungal pathogen panel

Author

Danièle Maubon, Muriel Cornet, Cécile Garnaud, Céline Dard, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de parasitologie-mycologie, and CHU Grenoble

Subjects
0301 basic medicine, medicine.medical_specialty, antifungal stewardship, diagnosis, 030106 microbiology, Context (language use), invasive fungal infection, blood culture, Pathology and Forensic Medicine, Sepsis, 03 medical and health sciences, Health care, Genetics, Humans, Medicine, Blood culture, Intensive care medicine, Molecular Biology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Fungemia, medicine.diagnostic_test, business.industry, candidemia, Fungi, Reproducibility of Results, molecular diagnostic, Fungal pathogen, medicine.disease, 3. Good health, PCR, Molecular Diagnostic Techniques, Mycoses, Molecular Medicine, Identification (biology), Reagent Kits, Diagnostic, Stewardship, business
Abstract

International audience; Fungemia presents high morbi-mortality and thus rapid microbiological diagnosis may contribute to appropriate patient management. In the last decade, kits based on molecular technologies have become available and health care institutes are increasingly facing critical investment choices. Although all these tools aim to achieve rapid fungal detection and species identification, they display different inherent characteristics. Areas covered: Considering technologies allowing detection and identification of fungal species in a sepsis context, the market proposes either tests on positive blood culture or tests on patient's whole blood. In this review, the authors describe and compare the ePlex® Blood Culture Identification Fungal Pathogen (BCID-FP) test, a fully automated one-step single-use cartridge assay that has been designed to detect identify frequent or rare but emerging, fungal species, from positive blood culture. A comparison with the competing kits is provided. Expert commentaries: The ePlex BCID-FP test provides a diversified and rather relevant panel. Its easy-to-use cartridges allow flexible use around the clock. Nevertheless, prospective clinical studies assessing the time-to-result benefit on antifungal stewardship and on hospital length of stay are not available yet. New tools aim to benefit clinicians and patients, but they should be accompanied by supervision of result interpretation and adaptation of antifungal stewardship.

Published
2017
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39. Integrating anatomo‐physiological changes and pharmacogenomics in anti‐infective therapy management: is it a major concern?

Author

Pierrick Bedouch, Hélène Pluchart, Elodie Gautier-Veyret, Sébastien Chanoine, Xavier Fonrose, Laura Beaumier, Marie-Pierre Brenier-Pinchart, Boubou Camara, and Muriel Cornet

Subjects
Adult, Azoles, medicine.medical_specialty, Anorexia Nervosa, Antifungal Agents, Administration, Oral, Context (language use), Case Reports, Polymorphism, Single Nucleotide, 030226 pharmacology & pharmacy, Anti-infective therapy, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Intensive care medicine, Pharmacology, business.industry, Chronic pulmonary aspergillosis, medicine.disease, Pharmacogenomic Testing, Cytochrome P-450 CYP2C19, Management strategy, Treatment Outcome, Intestinal Absorption, Anorexia nervosa (differential diagnoses), Pharmacogenomics, Female, Pulmonary Aspergillosis, business
Abstract

Success of anti‐infective therapy is a major challenge in some patients given anatomo‐physiological changes and genetic variations. In this case anecdote, we report the management strategy of a patient suffering from chronic pulmonary aspergillosis in a context of anorexia nervosa and genetic polymorphism. [Image: see text]

Published
2018
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40. Dermatophyte infection caused by Nannizzia gypsea : A rare case report from Madagascar

Author

Njariharinjakamampionona Rakotozandrindrainy, Tahinamandranto Rasamoelina, Norosoa Julie Zafindraibe, Christian Rafalimanana, Lala Rasoamialy Razanakolona, Abel Hermann Soankasina, Mala Rakoto Andrianarivelo, Solohery Andrianteloasy, Muriel Cornet, and Andry Rasamindrakotroka

Subjects
0301 basic medicine, medicine.medical_specialty, Nannizzia gypsea, 030106 microbiology, Case Report, Microsporum gypseum, medicine.disease_cause, Microbiology, Lesion, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Rare case, Madagascar, medicine, Internal transcribed spacer, lcsh:QH301-705.5, Dermatophyte infection, lcsh:R5-920, business.industry, ITS region, medicine.disease, Dermatology, Infectious Diseases, lcsh:Biology (General), Dermatophyte, Tinea capitis, Miconazole, medicine.symptom, lcsh:Medicine (General), business, medicine.drug
Abstract

We report a rare case of dermatophyte infection of the glabrous skin (Tinea corporis) caused by Nannizzia gypsea (formerly Microsporum gypseum). A 22-year-old Malagasy female who reported close contact reportedly with cats, presented a single round lesion with a peripheral, active, squamous and pruriginous inflammatory bead. Morphologic species identification was confirmed by sequencing the internal transcribed spacer (ITS) region of the genome. Specific treatment with oral loratadine and topical miconazole cream was effective. Keywords: Nannizzia gypsea, Dermatophyte infection, ITS region, Madagascar

Published
2018
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41. Self-nanoemulsifying drug delivery system to improve transcorneal permeability of voriconazole: in-vivo studies

Author

Zoarilala Rinah Razafindrakoto, Souad Sfar, Muriel Cornet, Raja Chaâbane-Banaoues, Karim Miladi, Bakoliarisoa Nivomalala Voahangy Rasoanirina, David Ramanitrahasimbola, and Mohamed Ali Lassoued

Subjects
Antifungal Agents, Cmax, Pharmaceutical Science, Biological Availability, Polysorbates, Administration, Ophthalmic, 02 engineering and technology, Microbial Sensitivity Tests, Pharmacology, Permeability, Nanocomposites, Polyethylene Glycols, 03 medical and health sciences, Minimum inhibitory concentration, chemistry.chemical_compound, Surface-Active Agents, 0302 clinical medicine, Drug Delivery Systems, Pharmacokinetics, In vivo, medicine, Animals, Isopropyl myristate, Hexoses, Voriconazole, Myristates, Chemistry, 021001 nanoscience & nanotechnology, Drug Liberation, Drug delivery, 030221 ophthalmology & optometry, Draize test, Emulsions, Rabbits, 0210 nano-technology, Eye Infections, Fungal, medicine.drug
Abstract

Objective This study investigates the effectiveness of self-nanoemulsifying drug delivery system (SNEDDS) in improving voriconazole transcorneal permeability. Methods Voriconazole-SNEDDS was prepared with isopropyl myristate, PEG 400, Tween 80® and Span 80® and was subjected for physicochemical characterization after reconstitution with NaCl 0.9% (1/9; v/v). In-vitro antifungal activity was assessed and compared with the marketed formulation. In-vivo studies, namely ocular irritation test via modified Draize test and pharmacokinetic study, were investigated using rabbit as animal model. Key findings Voriconazole-SNEDDS presented a droplet size of 21.353 ± 0.065 nm, a polydispersity index of 0.123 ± 0.003, a pH of 7.205 ± 0.006 and an osmolarity of 342.667 ± 2.517 mOsmol/l after reconstitution with NaCl 0.9%. Voriconazole-SNEDDS minimum inhibitory concentration (MIC90) was similar to the one of marketed formulation for Candida species while it was significantly lower (P < 0.001) for Aspergillus fumigatus. Draize test revealed that Voriconazole-SNEDDS was safe for ocular administration. Voriconazole maximum concentration (5.577 ± 0.852 µg/ml) from SNEDDS was higher than marketed formulation (Cmax = 4.307 ± 0.623 µg/ml), and the Tmax was delayed to 2 h. The area under the concentration–time curve value of Voriconazole-SNEDDS was improved by 2.419-fold. Conclusion Our results suggest that SNEDDS is a promising carrier for voriconazole ocular delivery and this encourages further clinical studies.

Published
2019

42. Treatment by Posaconazole Tablets, Compared to Posaconazole Suspension, Does Not Reduce Variability of Posaconazole Trough Concentrations

Author

Elodie Gautier-Veyret, Anne Thiebaut-Bertrand, Françoise Stanke-Labesque, Matthieu Roustit, Léa Bolcato, Muriel Cornet, Marie-Pierre Brenier-Pinchart, Julia Tonini, and Stéphanie Weiss

Subjects
Adult, Diarrhea, Male, Percentile, medicine.medical_specialty, Linear mixed effect model, Posaconazole, Antifungal Agents, Administration, Oral, Gastroenterology, Drug Administration Schedule, 03 medical and health sciences, Cmin, Suspensions, Risk Factors, Internal medicine, medicine, Humans, Transplantation, Homologous, Pharmacology (medical), Trough Concentration, Aged, Retrospective Studies, 030304 developmental biology, Pharmacology, Analysis of Variance, 0303 health sciences, Univariate analysis, medicine.diagnostic_test, 030306 microbiology, business.industry, Age Factors, Hematopoietic Stem Cell Transplantation, Liter, Middle Aged, Triazoles, Infectious Diseases, Mycoses, Therapeutic drug monitoring, Hematologic Neoplasms, Female, Drug Monitoring, business, Tablets, medicine.drug
Abstract

The delayed-release tablet formulation of posaconazole (POS-tab) results in higher plasma POS trough concentrations (C(min)) than the oral suspension (POS-susp), which raises the question of the utility of therapeutic drug monitoring (TDM). We aimed to compare the variability of the POS C(min) for the two formulations and identify determinants of the POS-tab C(min) and its variability. Demographic, biological, and clinical data from 77 allogeneic hematopoietic stem cell transplant patients (874 C(min)) treated with POS-tab (n = 41), POS-susp (n = 29), or both (n = 7) from January 2015 to December 2016 were collected retrospectively. Interpatient and within-subject coefficients of variation (CVs) of the C(min) adjusted to dose (D) were calculated for each formulation. Between-group comparisons were performed using a linear mixed effects model. The POS C(min) was higher for the tablet than for the suspension (median [25th–75th percentile]: 1.8 [1.2–2.4] mg/liter versus 1.2 [0.7–1.6] mg/liter, P

Published
2019
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43. The Diagnosis of Fungal Neglected Tropical Diseases (Fungal NTDs) and the Role of Investigation and Laboratory Tests: An Expert Consensus Report

Author

Ahmed H. Fahal, Beatriz L. Gómez, Wendy W. J. van de Sande, Tom Chiller, Arunaloke Chakrabarti, David W. Denning, Flavio Queiroz-Telles, E.E. Zijlstra, Alexandro Bonifaz, Anisa Mosam, Beatriz Bustamante, Fahafahantsoa Rapelanoro Rabenja, Karlyn D. Beer, Roberto Estrada, Yesholata Mahabeer, Muriel Cornet, Ruoyu Li, María de Guadalupe Chávez-López, Guadalupe Estrada-Chávez, Roderick J. Hay, Mala Rakoto Andrianarivelo, Lala Soavina Ramarozatovo, and Medical Microbiology & Infectious Diseases

Subjects
Laboratory test, medicine.medical_specialty, Consensus, Tropical disease, Biopsy, Point-of-care testing, Health care utilization, Impression material, Histopathology, lcsh:Medicine, sporotrichosis, Article, chromoblastomycosis, Mycosis, fungal NTDs, Integrated approaches, SDG 3 - Good Health and Well-being, integrated approaches, Fungal ntds, medicine, Mycetoma, Intensive care medicine, laboratory diagnosis, Point of care testing, Microscopy, Chromoblastomycosis, Fungus culture, General Immunology and Microbiology, Sporotrichosis, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Expert consensus, Chromomycosis, Patient referral, Nonhuman, medicine.disease, Infectious Diseases, Laboratory diagnosis, Neglected tropical diseases, Neglected disease, business, mycetoma, Human
Abstract

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs. © 2019 by the authors.

Published
2019
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44. Prevalence, geographic risk factor, and development of a standardized protocol for fungal isolation in cystic fibrosis: Results from the international prospective study 'MFIP'

Author

Laurence Delhaes, Florent Morio, Wieland Meyer, Jean-Philippe Bouchara, A. Biffi, E. Manso, Gabriella Ricciotti, Rafael Cantón, Patrice Le Pape, Gilles Nevez, Maiz-Luis Carro, Kada Touati, Walter Buzina, Lisa Cariani, Ersilia Fiscarelli, Marc Pihet, Elia Gómez, Frédéric Grenouillet, Françoise Botterel, Veroniek Saegeman, Muriel Cornet, Alain Duhamel, Silvia Campana, Solène Le Gal, Katrien Lagrou, Odile Faure-Cognet, Eric Dannaoui, Sharon C.-A. Chen, Andrew M. Borman, Emmanuel Roilides, Loïc Favennec, Maria Simitsopoulou, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), Laboratoire de Parasitologie-Mycologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université de Reims Champagne-Ardenne (URCA), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), Université d'Angers (UA), Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Mycology Reference Laboratory, Health Protection Agency, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), The University of Sydney, Third Department of Pediatrics, Aristotle University, Ippokration Hospital of Thessaloniki, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, and Children's Hospital Bambino Gesù IRCCS [Rome]

Subjects
Male, Microbiological Techniques, 0301 basic medicine, Cystic Fibrosis, International Cooperation, [SDV]Life Sciences [q-bio], Cystic fibrosis, Aspergillus fumigatus, Molds, 0302 clinical medicine, Risk Factors, Prevalence, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, education.field_of_study, biology, 3. Good health, Aspergillus, Female, medicine.symptom, Cladosporium, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Filamentous fungi, Lung mycobiota, Population, Context (language use), Specimen Handling, 03 medical and health sciences, Internal medicine, Mycological examination, medicine, Humans, education, Lung Diseases, Fungal, business.industry, Fungi, Sputum, Reproducibility of Results, medicine.disease, biology.organism_classification, Culture Media, 030104 developmental biology, 030228 respiratory system, Pediatrics, Perinatology and Child Health, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

© 2018 Background: Fungi are increasingly recognized for their potential role in contributing to pulmonary damage in Cystic Fibrosis (CF). We therefore designed a prospective international study aimed at (i) determining the prevalence of fungi isolated from sputum samples collected from a large CF population, (ii) comparing the performance of different media used for fungal culture, and (iii) proposing a standardized protocol suitable for CF routine microbiology. Methods: An international, consensually designed prospective study was set up (https://www.ecfs.eu/special-projects/mucofong-international-project). All centers worked according to the same protocol approved by Lille Ethical Committee. CF sputa were inoculated onto eight semi-selective media incubated at 37 °C or 25 °C–30 °C for 15 days, and inspected twice weekly for fungal growth. Results: A total of 469 sputa were collected from patients at 18 European and one Australian CF centers. Positive cultures for fungal growth were significantly associated with patient ages. Aspergillus fumigatus was the most frequently isolated mold. We identified a growing European North-to-South gradient of Scedosporium prevalence, while yeasts, Aspergillus section Fumigati, Cladosporium and Penicillium were significantly more prevalent in the Northern regions. Conclusions: According to the CHi-squared Automatic Interaction Detector method, we propose a consensual protocol based on two media (YPDA or Sabouraud medium, and B(+) medium) to detect the main opportunistic molds in CF context; the use of an additional medium being recommended according to the patient's clinical status. This standardized protocol allows us to have an accurate overview of the respiratory mycobiome on the culturomic side in CF. ispartof: JOURNAL OF CYSTIC FIBROSIS vol:18 issue:2 pages:212-220 ispartof: location:Netherlands status: published

Published
2019
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45. Impact of bronchial colonization with Candida spp. on the risk of bacterial ventilator-associated pneumonia in the ICU: the FUNGIBACT prospective cohort study

Author

Marie-Christine Jacob, Christiane Forrestier, Stéphane Ruckly, Muriel Cornet, Philippe Poirier, Lenka Styfalova, Jean-François Timsit, Carole Schwebel, Bertrand Souweine, Clinique de réanimation médicale, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-Hôpital Michallon, Centre Hospitalier Universitaire [Grenoble] (CHU), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Immunocytologie, EFS, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, and Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, medicine.medical_specialty, Organ Dysfunction Scores, medicine.medical_treatment, Bronchi, Critical Care and Intensive Care Medicine, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Sepsis, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, medicine, Humans, Colonization, Prospective Studies, Simplified Acute Physiology Score, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Candida, Mechanical ventilation, business.industry, Ventilator-associated pneumonia, Candidiasis, Pneumonia, Ventilator-Associated, 030208 emergency & critical care medicine, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Pneumonia, Intensive Care Units, 030228 respiratory system, SAPS II, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Respiratory tract Candida spp. colonization is associated with more frequent bacterial ventilator-associated pneumonia (VAP). However, this colonization could be causally related to VAP or simply reflect the immune paralysis associated with multiple organ failure. To prospectively evaluate the relationship between Candida spp. colonization and bacterial VAP in mechanically ventilated patients with multiple organ failure. Patients receiving mechanical ventilation for > 4 days and presenting multiple organ failure were included. Tracheal colonization with Candida spp. was evaluated at inclusion (day 0, D0) and every 4 days until extubation. Quantitative proximal and tracheal cultures were performed at each VAP episode. Monocyte human leukocyte antigen-DR isotype (mHLA-DR) expression and the ratio of polymononuclear leukocytes to lymphocytes were used to evaluate immunoparalysis at D0 and D7. The relationship between fungal colonization and VAP was modelled using cause-specific models for repeated events with adjustment for time-dependent confounders and immune factors. A total of 213 patients, with a median age of 64, simplified acute physiology score II (SAPS II) score 55 and sequential organ failure assessment (SOFA) score 10, mainly admitted for medical reasons (n = 197, 92%), were enrolled in 2012–2015. The median ICU stay was 24 days and the mortality rate was 32% (69 cases). Median mHLA-DR was 5916 Ab-bound/cell [3863–8934]; median lymphocyte count, 0.9Giga/L [0.6–1.3]; neutrophil-to-lymphocyte ratio, 10.9 [6.5–19.7]. Overall, 146 cases (68.5%) had tracheal colonization with Candida spp. An episode of VAP occurred (either for the first or only time) in 62 (29.1%) cases 5.5 days (median) after D0; a second episode occurred in 12 (5.6%) cases, 15.5 days (median) after D0. After adjustment, bronchial colonization with Candida was not associated with VAP [adjusted cause-specific hazard ratio = 0.98 (0.59–1.65), p = 0.95]. In patients with mechanical ventilation for more than 4 days and multiple organ failure, bronchial colonization with Candida spp. was not associated with VAP, even after adjustment for immune function.

Published
2018
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46. Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings

Author

Bruno Hochhegger, Samihah Moazam, Nasilele F Simukulwa, Cecilia M Jude, NK Irurhe, Iain D. Page, Donald C. Cole, Alena Skrahina, Richard Sawyer, Koichi Izumikawa, Bayu A. P. Wilopo, Charlotte Sriruttan, Anna Rozaliyani, Bruce Kirenga, Findra Setianingrum, Jeremiah Chakaya, David W. Denning, Haileyesus Getahun, Muriel Cornet, Paul Bowyer, Helmut J. F. Salzer, Veronica Manduku, Malcolm Richardson, Arunaloke Chakrabarti, Rita O. Oladele, John Abuga Guto, Muhammad Irfan, Ana Alastruey-Izquierdo, Juan Luis Rodríguez Tudela, Martin Hoenigl, Sara Gago, Felix Bongomin, and Kauser Jabeen

Subjects
0301 basic medicine, Pediatrics, Epidemiology, lcsh:Medicine, Medical microbiology, Fibrosis, antibody, Lung, resource-constrained settings, Chronic pulmonary aspergillosis, aspergilloma, imaging, Online Report, Infectious Diseases, Aspergillus, Medical Microbiology, Practice Guidelines as Topic, Public Health and Health Services, Infection, Aspergilloma, Microbiology (medical), medicine.medical_specialty, Tuberculosis, Clinical Sciences, 030106 microbiology, Resource constrained, Microbiology, World health, lcsh:Infectious and parasitic diseases, Vaccine Related, 03 medical and health sciences, Rare Diseases, Aspergillosis/*diagnosis/*pathology, Biodefense, medicine, Humans, lcsh:RC109-216, business.industry, Prevention, lcsh:R, developing countries, medicine.disease, Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings, tuberculosis and other mycobacteria, Emerging Infectious Diseases, Good Health and Well Being, Socioeconomic Factors, Chronic Disease, fungi, Pulmonary Aspergillosis, Complication, business
Abstract

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

Published
2018
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47. Added Value of Next-Generation Sequencing for Multilocus Sequence Typing Analysis of a Pneumocystis jirovecii Pneumonia Outbreak1

Author

Patricia Pavese, Sébastien Bailly, Claire Wintenberger, Cécile Garnaud, Caroline Augier, Anne Thiebaut-Bertrand, Sylvie Larrat, Thibault Drouet, Marie-Reine Mallaret, Olivier Epaulard, Danièle Maubon, Eléna Charpentier, John Rendu, Paolo Malvezzi, Muriel Cornet, Jean-Benjamin Murat, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), INSERM U836, équipe 4, Muscles et pathologies, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Biochimie et Génétique Moléculaire, CHU Grenoble-Hôpital Michallon-CHU Grenoble-Hôpital Michallon, Service des Maladies Infectieuses, CHU Grenoble, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Clinique Universitaire d'Hématologie [La Tronche, Grenoble], Centre Hospitalier Universitaire [Grenoble] (CHU), Unité d'hygiène Hospitalière, Department of infectious diseases, Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), 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 [2016-2019] (UGA [2016-2019]), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Male, 0301 basic medicine, transplants, Epidemiology, multilocus sequence typing, Pneumocystis carinii, Pneumocystis pneumonia, Disease Outbreaks, Genotype, Pneumocystosis, high-throughput nucleotide sequencing, Child, Pneumocystis jirovecii, Phylogeny, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, biology, Pneumonia, Pneumocystis, Middle Aged, 3. Good health, Infectious Diseases, NGS, Child, Preschool, Synopsis, Female, MLST, Adult, Microbiology (medical), Adolescent, 030106 microbiology, Sensitivity and Specificity, DNA sequencing, pneumocystosis, respiratory infections, Young Adult, 03 medical and health sciences, medicine, pneumonia, Humans, Genotyping, Aged, Polymorphism, Genetic, Added Value of Next-Generation Sequencing for Multilocus Sequence Typing Analysis of a Pneumocystis jirovecii Pneumonia Outbreak, Computational Biology, Infant, Outbreak, biology.organism_classification, medicine.disease, Virology, Case-Control Studies, Multilocus sequence typing, next-generation sequencing, fungi
Abstract

Pneumocystis jirovecii is a major threat for immunocompromised patients, and clusters of pneumocystis pneumonia (PCP) have been increasingly described in transplant units during the past decade. Exploring an outbreak transmission network requires complementary spatiotemporal and strain-typing approaches. We analyzed a PCP outbreak and demonstrated the added value of next-generation sequencing (NGS) for the multilocus sequence typing (MLST) study of P. jirovecii strains. Thirty-two PCP patients were included. Among the 12 solid organ transplant patients, 5 shared a major and unique genotype that was also found as a minor strain in a sixth patient. A transmission map analysis strengthened the suspicion of nosocomial acquisition of this strain for the 6 patients. NGS-MLST enables accurate determination of subpopulation, which allowed excluding other patients from the transmission network. NGS-MLST genotyping approach was essential to deciphering this outbreak. This innovative approach brings new insights for future epidemiologic studies on this uncultivable opportunistic fungus.

Published
2017
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48. Population pharmacokinetics of micafungin in ICU patients with sepsis and mechanical ventilation

Author

Pierre Emmanuel Charles, Fabrice Bruneel, Samir Jaber, Joel Cousson, Muriel Cornet, Arnaud Foucrier, Jean-Louis Trouillet, Maité Garrouste-Orgeas, Thomas Le Saux, Vincent Jullien, Martin Cour, Ferhat Meziani, Elie Azoulay, Stéphane Ruckly, Michael Darmon, Carole Schwebel, Jean-François Timsit, Bertrand Souweine, Adeline Paris, Vincent Das, Bernard Allaouchiche, Jean-Pierre Gangneux, Kadda Klouche, Jean-Christophe Navellou, Didier Gruson, Michel Wolff, Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Réanimation Médicale [Grenoble], Hôpital Michallon-CHU Grenoble, Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Réanimation Médicale (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), 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), Département d'anesthésie-réanimation[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Service de réanimation [CH Versailles], Centre Hospitalier de Versailles André Mignot (CHV), Continental Automotive France [Toulouse], Service de réanimation médicale, Centre Hospitalier Universitaire de Reims (CHU Reims), Département d'Endocrinologie et Nutrition (LOUVAIN - Endocrino), Université Catholique de Louvain = Catholic University of Louvain (UCL), CSE, Centre européen de sociologie et de science politique (CESSP), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), Epidémiologie pronostique des cancers et affections graves, Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Réanimation médicale [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Reanimation Médicale et Infectieuse [Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat-Claude Bernard, Service de Réanimation, Hospices Civils de Lyon (HCL)-Hôpital E. Herriot, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Space Science Institute [Boulder] (SSI), Unité de Soins Intensifs et de Maladies Infectieuses, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], University of Grenoble 1/Albert Michallon university hospital, Astellas company, Génétique, pharmacologie et physiopathologie des maladies cardiovasculaires [CHU Pitié-Salpétriêre], Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Grenoble-Hôpital Michallon, École normale supérieure - Paris (ENS-PSL), Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Strasbourg, CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), 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 ), 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), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Epilepsies de l'Enfant et Plasticité Cérébrale ( U1129 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris Descartes - Paris 5 ( UPD5 ), Hopital Saint Louis Paris, CHU Saint Louis [APHP], Service de Réanimation Médicale, CHU Grenoble-Hôpital Albert Michallon, École normale supérieure - Paris ( ENS Paris ), Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), 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 ), 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 ), Université Montpellier 1 ( UM1 ) -Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui de Chauliac, Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] ( PhyMedExp ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition ( ICAN ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Pitié-Salpêtrière [APHP], réanimation chirurgicale, CH Versailles, Ministère de la santé, Continental Automotive France SA, Centre Hospitalier Universitaire de Reims ( CHU Reims ), Département d'Endocrinologie et Nutrition ( LOUVAIN - Endocrino ), Université Catholique de Louvain ( UCL ), Centre européen de sociologie et de science politique ( CESSP ), Université Panthéon-Sorbonne ( UP1 ) -École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Panthéon-Sorbonne ( UP1 ) -École des hautes études en sciences sociales ( EHESS ) -Centre National de la Recherche Scientifique ( CNRS ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat-Claude Bernard, Hospices Civils de Lyon ( HCL ) -Hôpital E. Herriot, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut de recherche, santé, environnement et travail ( Irset ), Université d'Angers ( UA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -École des Hautes Études en Santé Publique [EHESP] ( EHESP ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) -Université des Antilles ( UA ), Space Science Institute [Boulder] ( SSI ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), and Cornet, Muriel

Subjects
Male, 0301 basic medicine, Antifungal Agents, Candida parapsilosis, 030226 pharmacology & pharmacy, Gastroenterology, Plasma, Echinocandins, 0302 clinical medicine, Caspofungin, Medicine, Pharmacology (medical), Candida albicans, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Candida, Aged, 80 and over, biology, Middle Aged, 3. Good health, Intensive Care Units, Infectious Diseases, Anesthesia, Female, SOFA score, Monte Carlo Method, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, Microbial Sensitivity Tests, Lipopeptides, 03 medical and health sciences, Pharmacokinetics, Internal medicine, Humans, Intensive care unit, Healthy volunteers, Aged, Pharmacology, Candida glabrata, business.industry, Adult patients, Micafungin, Candidemia, biology.organism_classification, [SDV.MP.MYC] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Respiration, Artificial, NONMEM, Pharmacodynamics, Critically-ill patients, business
Abstract

International audience; Objectives: To identify the factors associated with the interindividual pharmacokinetic (PK) variability of micafungin and to evaluate the probability of reaching the previously determined PK/pharmacodynamic efficacy thresholds (AUC/MIC >5000 for non-parapsilosis Candida sp. and ≥285 for Candida parapsilosis) with the recommended 100 mg daily dose in ICU patients with sepsis and mechanical ventilation.Methods: One hundred patients were included and 436 concentrations were available for PK analysis performed with NONMEM software. PTA was determined by Monte Carlo simulations.Results: Micafungin obeyed a two-compartment model with first-order elimination from the central compartment. Mean parameter estimates (percentage interindividual variability) were 1.34 L/h (34%) for clearance (CL), 11.80 L (38%) and 7.68 L (39%) for central (Vc) and peripheral (Vp) distribution volumes, respectively, and 4.67 L/h (37%) for distribution clearance. CL, Vc and Vp increased by 14% when the albumin level was ≤25 g/L and CL decreased by 25% when SOFA score was ≥10. Body weight was related to CL, Vc and Vp by allometric models. PTA was ≥90% in Candida albicans and Candida glabrata infections, except when the MIC was ≥0.015 mg/L, and ranged between 0% and 40% for C. parapsilosis infections with MIC ≥0.5 mg/L.Conclusions: A possible increase in the dose should be evaluated for infections due to C. parapsilosis and for infections due to C. albicans and C. glabrata with MICs ≥0.015 mg/L.

Published
2017
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49. Borrelia crociduraeMeningoencephalitis, West Africa

Author

Amina Bourahoui, Annick Bosseray, Natacha Sertour, Martine Garnier, Sandrine Goutier, Elisabeth Ferquel, Hervé Pelloux, Patricia Pavese, G. Couetdic, Bruno Hoen, Isabelle Pelloux, Muriel Cornet, Claudine Pinel, Claire Lapostolle, Centre National de Référence des Borrelia (CNR), Institut Pasteur [Paris], Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de parasitologie-mycologie, CHU Grenoble, Clinique de médecine interne, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Laboratoire de Bactériologie, Service des Maladies Infectieuses, 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 National de Référence des Borrelia ( CNR ), Grenoble Institut des Neurosciences ( GIN ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Grenoble-Université Joseph Fourier - Grenoble 1 ( UJF ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, 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), Laboratoire Chrono-environnement (UMR 6249) (LCE), 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, Endemic Diseases, relapsing fever, Epidemiology, encephalitis, lcsh:Medicine, spirochete, Disease, Polymerase Chain Reaction, West africa, tick-borne relapsing fever, 0302 clinical medicine, Lyme disease, Meningoencephalitis, RNA, Ribosomal, 16S, Ornithodoros ticks, bacteria, Child, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Borrelia meningitis, Doxycycline, Travel, 0303 health sciences, Ceftriaxone, Dispatch, Relapsing Fever, meningitis, Middle Aged, Senegal, 3. Good health, RNA, Bacterial, Infectious Diseases, Molecular Diagnostic Techniques, Female, France, medicine.drug, Adult, Microbiology (medical), medicine.medical_specialty, 030231 tropical medicine, Biology, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Borrelia, molecular diagnosis, West Africa, medicine, Humans, lcsh:RC109-216, 030306 microbiology, lcsh:R, Sequence Analysis, DNA, medicine.disease, biology.organism_classification, Dermatology, Borrelia crocidurae, Immunology
Abstract

International audience; Borrelia crocidurae-associated relapsing fever is endemic to West Africa and is considered benign. We report 4 patients with B. crocidurae-associated neurologic symptoms; 2 of their cases had been misdiagnosed. Frequency and severity of this disease could be underestimated; molecular methods and serodiagnostic tests for Lyme disease might be helpful in its detection.

Published
2013
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50. Rapid Fatal Outcome of Cryptococcal Meningoencephalitis in a Non-HIV Immunocompromised Patient with a Low Fluconazole Susceptibility Isolate: A Case Report from Madagascar

Author

Muriel Cornet, Philippe Vanhems, Rivonirina Andry Rakotoarivelo, Tiana Razafinambinintsoa, Thomas Bénet, Njary Randriamampionona, Mihaja Raberahona, Mala Rakoto-Andrianarivelo, Mamy Jean de Dieu Randria, Angelot F. Rakotomalala, Hygiène Hospitalière et Epidémiologie, Hospices Civils de Lyon (HCL), Groupement Hospitalier Edouard Herriot Hospices Civils de Lyon, Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), 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 Grenoble Alpes [2016-2019] (UGA [2016-2019])-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 Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Université d'Antananarivo

Subjects
0301 basic medicine, medicine.medical_specialty, Pediatrics, Fatal outcome, Case Report, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, lcsh:RC109-216, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, business.industry, Cryptococcal meningoencephalitis, Immunocompromised patient, General Medicine, medicine.disease, 3. Good health, 030104 developmental biology, Cryptococcosis, Immunology, business, Fluconazole, medicine.drug
Abstract

Cryptococcal meningoencephalitis is considered rare in HIV-negative individuals. In Madagascar, the epidemiology of cryptococcosis has not yet been well described, neither in immunocompetent nor in immunocompromised patients. We report here the first Malagasy detailed case of cryptococcal meningoencephalitis in a non-HIV immunocompromised adult patient carrying a low fluconazole susceptibility isolate. We emphasize the importance of early and accurate diagnosis to meet the challenges of managing cryptococcosis in developing countries.

Published
2016
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