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1. Decoding the historical tale: COVID-19 impact on haematological malignancy patients—EPICOVIDEHA insights from 2020 to 2022Research in context

Author

Jon Salmanton-García, Francesco Marchesi, Francesca Farina, Barbora Weinbergerová, Federico Itri, Julio Dávila-Valls, Sonia Martín-Pérez, Andreas Glenthøj, Ditte Stampe Hersby, Maria Gomes da Silva, Raquel Nunes Rodrigues, Alberto López-García, Raúl Córdoba, Yavuz M. Bilgin, Iker Falces-Romero, Shaimaa El-Ashwah, Ziad Emarah, Caroline Besson, Milena Kohn, Jaap Van Doesum, Emanuele Ammatuna, Monia Marchetti, Jorge Labrador, Giovanni Paolo Maria Zambrotta, Luisa Verga, Ozren Jaksic, Marcio Nucci, Klára Piukovics, Alba Cabirta-Touzón, Moraima Jiménez, Elena Arellano, Ildefonso Espigado, Ola Blennow, Anna Nordlander, Stef Meers, Jens van Praet, Tommaso Francesco Aiello, Carolina Garcia-Vidal, Nicola Fracchiolla, Mariarita Sciumè, Guldane Cengiz Seval, Pavel Žák, Caterina Buquicchio, Carlo Tascini, Stefanie K. Gräfe, Martin Schönlein, Tatjana Adžić-Vukičević, Valentina Bonuomo, Chiara Cattaneo, Summiya Nizamuddin, Martin Čerňan, Gaëtan Plantefeve, Romane Prin, Tomas Szotkovski, Graham P. Collins, Michelina Dargenio, Verena Petzer, Dominik Wolf, Natasha Čolović, Lucia Prezioso, Toni Valković, Francesco Passamonti, Gustavo-Adolfo Méndez, Uluhan Sili, Antonio Vena, Martina Bavastro, Alessandro Limongelli, Rafael F. Duarte, Marie-Pierre Ledoux, Milche Cvetanoski, Zlate Stojanoski, Marina Machado, Josip Batinić, Gabriele Magliano, Monika M. Biernat, Nikola Pantić, Christian Bjørn Poulsen, Annarosa Cuccaro, Maria Ilaria Del Principe, Austin Kulasekararaj, Irati Ormazabal-Vélez, Alessandro Busca, Fatih Demirkan, Marriyam Ijaz, Nikolai Klimko, Igor Stoma, Sofya Khostelidi, Noemí Fernández, Ali S. Omrani, Rui Bergantim, Nick De Jonge, Guillemette Fouquet, Milan Navrátil, Ghaith Abu-Zeinah, Michail Samarkos, Johan Maertens, Cristina De Ramón, Anna Guidetti, Ferenc Magyari, Tomás José González-López, Tobias Lahmer, Olimpia Finizio, Natasha Ali, László Imre Pinczés, Esperanza Lavilla-Rubira, Alessandra Romano, Maria Merelli, Mario Delia, Maria Calbacho, Joseph Meletiadis, Darko Antić, José-Ángel Hernández-Rivas, Joyce Marques de Almeida, Murtadha Al-Khabori, Martin Hoenigl, Maria Chiara Tisi, Nina Khanna, Aleksandra Barać, Noha Eisa, Roberta Di Blasi, Raphaël Liévin, Carolina Miranda-Castillo, Nathan C. Bahr, Sylvain Lamure, Mario Virgilio Papa, Ayel Yahya, Avinash Aujayeb, Jan Novák, Nurettin Erben, María Fernández-Galán, José-María Ribera-Santa Susana, Ikhwan Rinaldi, Rita Fazzi, Monica Piedimonte, Rémy Duléry, Yung Gonzaga, Andrés Soto-Silva, Giuseppe Sapienza, Alexandra Serris, Ľuboš Drgoňa, Ana Groh, Laura Serrano, Eleni Gavriilaki, Athanasios Tragiannidis, Juergen Prattes, Nicola Coppola, Vladimir Otašević, Miloš Mladenović, Mirjana Mitrović, Bojana Mišković, Pavel Jindra, Sofia Zompi, Maria Vittoria Sacchi, Carolin Krekeler, Maria Stefania Infante, Daniel García-Bordallo, Gökçe Melis Çolak, Jiří Mayer, Marietta Nygaard, Michaela Hanáková, Zdeněk Ráčil, Matteo Bonanni, Philipp Koehler, Laman Rahimli, Oliver A. Cornely, Livio Pagano, Francisco Javier Martín-Vallejo, Przemyslaw Zdziarski, Hossein Zarrinfer, Jana Wittig, Sein Win, Vivien Wai-Man, Benjamín Víšek, Donald C. Vinh, Maria Vehreschild, Gina Varricchio, Panagiotis Tsirigotis, Ana Torres-Tienza, Alina Daniela Tanase, Agostino Tafuri, Maria Stamouli, Jiří Sramek, Carole Soussain, Ayten Shirinova, Jörg Schubert, Enrico Schalk, Mohammad Reza Salehi, Modar Saleh, Giorgio Rosati, Elisa Roldán, Florian Reizine, Mayara Rêgo, Isabel Regalado-Artamendi, Marina Popova, Fernando Pinto, Laure Philippe, Hans Martin Orth, Hans-Beier Ommen, Aleš Obr, Lucía Núñez-Martín-Buitrago, Nicolas Noël, Julia Neuhann, Gianpaolo Nadali, Julia A. Nacov, Ana M. Munhoz Alburquerque, Maria Enza Mitra, Malgorzata Mikulska, Sibylle Mellinghoff, Ben Mechtel, Juan-Alberto Martín-González, Sandra Malak, Jorge Loureiro-Amigo, Lisset Lorenzo De La Peña, Giulia Liberti, Marianne Landau, Ira Lacej, Martin Kolditz, Chi Shan Kho, Reham Abdelaziz Khedr, Meinolf Karthaus, Linda Katharina Karlsson, María-Josefa Jiménez-Lorenzo, Macarena Izuzquiza, Baerbel Hoell-Neugebauer, Raoul Herbrecht, Christopher H. Heath, Fabio Guolo, Jan Grothe, Antonio Giordano, Sergey Gerasymchuk, Ramón García-Sanz, Nicole García-Poutón, Vaneuza Araújo Moreira Funke, Monica Fung, Charlotte Flasshove, Luana Fianchi, Jenna Essame, Matthias Egger, Bernard Drenou, Giulia Dragonetti, Maximilian Desole, Roberta Della Pepa, Bénédicte Deau Fischer, Elizabeth De Kort, Erik De Cabo, François Danion, Etienne Daguindau, Tania Cushion, Louise Cremer, Marianna Criscuolo, Gregorio Cordini, Antonella Cingolani, Fabio Ciceri, Fazle Rabbi Chowdhury, Ekaterina Chelysheva, Adrien Chauchet, Louis Yi Ann Chai, M. Mansour Ceesay, Elena Busch, Mathias Brehon, Davimar M.M. Borducchi, Stephen Booth, Serge Bologna, Caroline Berg Venemyr, Rebeca Bailén-Almorox, Anastasia Antoniadou, Amalia N. Anastasopoulou, and Fevzi Altuntaş

Subjects
Vaccination, ICU, COVID-19, Haematological malignancy, Immunosuppression, Medicine (General), R5-920
Abstract

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Published
2024
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2. Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings

Author

Giuseppe Rossi, Jon Salmanton-García, Chiara Cattaneo, Francesco Marchesi, Julio Dávila-Valls, Sonia Martín-Pérez, Federico Itri, Alberto López-García, Andreas Glenthøj, Maria Gomes da Silva, Caroline Besson, Monia Marchetti, Barbora Weinbergerová, Ozren Jaksic, Moraima Jiménez, Yavuz M. Bilgin, Jaap Van Doesum, Francesca Farina, Pavel Žák, Luisa Verga, Graham P. Collins, Valentina Bonuomo, Jens Van Praet, Marcio Nucci, Stef Meers, Ildefonso Espigado, Nicola S. Fracchiolla, Toni Valković, Christian Bjørn Poulsen, Natasha Čolović, Giulia Dragonetti, Marie-Pierre Ledoux, Carlo Tascini, Caterina Buquicchio, Ola Blennow, Francesco Passamonti, Marina Machado, Jorge Labrador, Rafael F. Duarte, Martin Schönlein, Lucia Prezioso, Iker Falces-Romero, Austin Kulasekararaj, Carolina Garcia-Vidal, Noemí Fernández, Ghaith Abu-Zeinah, Irati Ormazabal-Vélez, Tatjana Adžić-Vukičević, Klára Piukovics, Igor Stoma, Annarosa Cuccaro, Gabriele Magliano, Tomáš Szotkowski, Tomás-José González-López, Shaimaa El-Ashwah, Rui Bergantim, Uluhan Sili, Johan Maertens, Fatih Demirkan, Cristina De Ramón, Verena Petzer, Maria Ilaria Del Principe, Milan Navrátil, Michelina Dargenio, Guldane Cengiz Seval, Michail Samarkos, Zdeněk Ráčil, László Imre Pinczés, Tobias Lahmer, Alessandro Busca, Gustavo-Adolfo Méndez, Antonio Vena, Monika M. Biernat, Maria Merelli, Maria Calbacho, Aleksandra Barać, Martina Bavastro, Alessandro Limongelli, Osman Ilhan, Dominik Wolf, Gökçe Melis Çolak, Ramón García-Sanz, Ziad Emarah, Bojana Mišković, Stefanie K. Gräfe, Miloš Mladenović, Tommaso Francesco Aiello, Lucía Núñez-Martín-Buitrago, Anna Nordlander, Elena Arellano, Giovanni Paolo Maria Zambrotta, Emanuele Ammatuna, Alba Cabirta, Maria Vittoria Sacchi, Raquel Nunes Rodrigues, Ditte Stampe Hersby, Michaela Hanakova, Laman Rahimli, Raul Cordoba, Oliver A. Cornely, Livio Pagano, Joyce MARQUES DE ALMEIDA, José-Ángel HERNÁNDEZ-RIVAS, Anna GUIDETTI, Olimpia FINIZIO, Zlate STOJANOSKI, Milche CVETANOSKI, Joseph MELETIADIS, Nick DE JONGE, Darko ANTIĆ, Natasha ALI, Maria Chiara TISI, Laura SERRANO, Gaëtan PLANTEFEVE, Nina KHANNA, Martin HOENIGL, Martin ČERŇAN, Carolina MIRANDA-CASTILLO, María FERNÁNDEZ-GALÁN, Alexandra SERRIS, Nurettin ERBEN, Rémy DULÉRY, Avinash AUJAYEB, Mario Virgilio PAPA, Jan NOVÁK, Mario DELIA, Giuseppe SAPIENZA, Florian REIZINE, Ali S. OMRANI, Roberta DI BLASI, Sylvain LAMURE, Ľuboš DRGOŇA, Nicola COPPOLA, Josip BATINIĆ, Murtadha AL-KHABORI, José-María RIBERA-SANTA SUSANA, Monica PIEDIMONTE, Jorge LOUREIRO-AMIGO, Guillemette FOUQUET, Rita FAZZI, François DANION, Jörg SCHUBERT, Baerbel HOELL-NEUGEBAUER, Nathan C. BAHR, Ayel Omar YAHIA, Ana TORRES-ATIENZA, Ikhwan RINALDI, Marina POPOVA, Hans-Beier OMMEN, Maria Enza MITRA, Malgorzata MIKULSKA, Ira LACEJ, Sofya KHOSTELIDI, Sein WIN, Donald VINH, Modar SALEH, Juergen PRATTES, Pavel JINDRA, Fabio GUOLO, Roberta DELLA PEPA, Ekaterina CHELYSHEVA, Przemyslaw ZDZIARSKI, Vivien WAI-MAN, Andrés SOTO-SILVA, Hans Martin ORTH, Sandra MALAK, Lisset LORENZO DE LA PEÑA, Martin KOLDITZ, Chi Shan KHO, Christopher H. HEATH, Ana GROH, Eleni GAVRIILAKI, Monica FUNG, Matthias EGGER, Elizabeth DE KORT, Erik DE CABO, Tania CUSHION, Fazle Rabbi CHOWDHURY, M. Mansour CEESAY, Mathias BREHON, Gina VARRICCHIO, Agostino TAFURI, María-Josefa JIMÉNEZ-LORENZO, Nikolai KLIMKO, Panagiotis TSIRIGOTIS, Anastasia ANTONIADOU, and Maria VEHRESCHILD

Subjects
Elderly, SARS-CoV-2, Hematological malignancy, High-risk patient, COVID-19, Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Published
2023
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4. COVID-19 infection in adult patients with hematological malignancies: a European Hematology Association Survey (EPICOVIDEHA)

Author

Livio Pagano, Jon Salmanton-García, Francesco Marchesi, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Nikolai Klimko, Philipp Koehler, Antonio Pagliuca, Francesco Passamonti, Luisa Verga, Benjamin Víšek, Osman Ilhan, Gianpaolo Nadali, Barbora Weinbergerová, Raúl Córdoba-Mascuñano, Monia Marchetti, Graham P. Collins, Francesca Farina, Chiara Cattaneo, Alba Cabirta, Maria Gomes-Silva, Federico Itri, Jaap van Doesum, Marie-Pierre Ledoux, Martin Čerňan, Ozren Jakšić, Rafael F. Duarte, Gabriele Magliano, Ali S. Omrani, Nicola S. Fracchiolla, Austin Kulasekararaj, Toni Valković, Christian Bjørn Poulsen, Marina Machado, Andreas Glenthøj, Igor Stoma, Zdeněk Ráčil, Klára Piukovics, Milan Navrátil, Ziad Emarah, Uluhan Sili, Johan Maertens, Ola Blennow, Rui Bergantim, Carolina García-Vidal, Lucia Prezioso, Anna Guidetti, Maria Ilaria del Principe, Marina Popova, Nick de Jonge, Irati Ormazabal-Vélez, Noemí Fernández, Iker Falces-Romero, Annarosa Cuccaro, Stef Meers, Caterina Buquicchio, Darko Antić, Murtadha Al-Khabori, Ramón García-Sanz, Monika M. Biernat, Maria Chiara Tisi, Ertan Sal, Laman Rahimli, Natasa Čolović, Martin Schönlein, Maria Calbacho, Carlo Tascini, Carolina Miranda-Castillo, Nina Khanna, Gustavo-Adolfo Méndez, Verena Petzer, Jan Novák, Caroline Besson, Rémy Duléry, Sylvain Lamure, Marcio Nucci, Giovanni Zambrotta, Pavel Žák, Guldane Cengiz Seval, Valentina Bonuomo, Jiří Mayer, Alberto López-García, Maria Vittoria Sacchi, Stephen Booth, Fabio Ciceri, Margherita Oberti, Marco Salvini, Macarena Izuzquiza, Raquel Nunes-Rodrigues, Emanuele Ammatuna, Aleš Obr, Raoul Herbrecht, Lucía Núñez-Martín-Buitrago, Valentina Mancini, Hawraa Shwaylia, Mariarita Sciumè, Jenna Essame, Marietta Nygaard, Josip Batinić, Yung Gonzaga, Isabel Regalado-Artamendi, Linda Katharina Karlsson, Maryia Shapetska, Michaela Hanakova, Shaimaa El-Ashwah, Zita Borbényi, Gökçe Melis Çolak, Anna Nordlander, Giulia Dragonetti, Alessio Maria Edoardo Maraglino, Amelia Rinaldi, Cristina De Ramón-Sánchez, Oliver A. Cornely, and EPICOVIDEHA working group

Subjects
COVID-19, Pandemic, Hematological malignancies, Epidemiology, EHA, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value

Published
2021
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5. COVID-19 in adult acute myeloid leukemia patients: a long-term follow-up study from the European Hematology Association survey (EPICOVIDEHA)

Author

Francesco Marchesi, Jon Salmanton-García, Ziad Emarah, Klára Piukovics, Marcio Nucci, Alberto López-García, Zdeněk Ráčil, Francesca Farina, Marina Popova, Sofia Zompi, Ernesta Audisio, Marie-Pierre Ledoux, Luisa Verga, Barbora Weinbergerová, Tomas Szotkovski, Maria Gomes Da Silva, Nicola Fracchiolla, Nick De Jonge, Graham Collins, Monia Marchetti, Gabriele Magliano, Carolina García-Vidal, Monika M. Biernat, Jaap Van Doesum, Marina Machado, Fatih Demirkan, Murtadha Al-Khabori, Pavel Žák, Benjamín Víšek, Igor Stoma, Gustavo-Adolfo Méndez, Johan Maertens, Nina Khanna, Ildefonso Espigado, Giulia Dragonetti, Luana Fianchi, Maria Ilaria Del Principe, Alba Cabirta, Irati Ormazabal-Vélez, Ozren Jaksic, Caterina Buquicchio, Valentina Bonuomo, Josip Batinić, Ali S. Omrani, Sylvain Lamure, Olimpia Finizio, Noemí Fernández, Iker Falces-Romero, Ola Blennow, Rui Bergantim, Natasha Ali, Sein Win, Jens Van Praet, Maria Chiara Tisi, Ayten Shirinova, Martin Schönlein, Juergen Prattes, Monica Piedimonte, Verena Petzer, Milan Navrátil, Austin Kulasekararaj, Pavel Jindra, Jiří Sramek, Andreas Glenthøj, Rita Fazzi, Cristina De Ramón-Sánchez, Chiara Cattaneo, Maria Calbacho, Nathan C. Bahr, Shaimaa El-Ashwah, Raul Cordoba, Michaela Hanakova, Giovanni Zambrotta, Mariarita Sciumè, Stephen Booth, Raquel Nunes Rodrigues, Maria Vittoria Sacchi, Nicole García-Poutón, Juan-Alberto Martín-González, Sofya Khostelidi, Stefanie Gräfe, Laman Rahimli, Emanuele Ammatuna, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Nikolai Klimko, Philipp Koehler, Antonio Pagliuca, Francesco Passamonti, Oliver A. Cornely, and Livio Pagano

Subjects
Diseases of the blood and blood-forming organs, RC633-647.5
Abstract

Patients with acute myeloid leukemia (AML) are at high risk of dying from coronavirus disease 2019 (COVID-19). The optimal management of AML patients with COVID-19 has not been established. Our multicenter study included 388 adult AML patients diagnosed with COVID-19 between February 2020 and October 2021. The vast majority were receiving or had received AML treatment in the preceding 3 months. COVID-19 was severe in 41.2% and critical in 21.1% of cases. The chemotherapeutic schedule was modified in 174 patients (44.8%), delayed in 68 and permanently discontinued in 106. After a median follow-up of 325 days, 180 patients (46.4%) had died; death was attributed to COVID-19 (43.3%), AML (26.1%) or to a combination of both (26.7%), whereas in 3.9% of cases the reason was unknown. Active disease, older age, and treatment discontinuation were associated with death, whereas AML treatment delay was protective. Seventy-nine patients had a simultaneous AML and COVID-19 diagnosis, with better survival when AML treatment could be delayed (80%; P

Published
2022
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6. Invasive Scedosporium spp. and Lomentospora prolificans infections in pediatric patients: Analysis of 55 cases from FungiScope® and the literature

Author

Danila Seidel, Angela Hassler, Jon Salmanton-García, Philipp Koehler, Sibylle C. Mellinghoff, Fabianne Carlesse, Matthew P. Cheng, Iker Falces-Romero, Raoul Herbrecht, Alfredo Jover Sáenz, Nikolai Klimko, Mihai Mareş, Cornelia Lass-Flörl, Pere Soler-Palacín, Hilmar Wisplinghoff, Oliver A. Cornely, Zoi Pana, and Thomas Lehrnbecher

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Objectives: Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections. Methods: Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected. Results: Fifty-five children (median age 9 years [IQR: 5–14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment.Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3–28] versus 61 days [IQR: 16–148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35–51.40] and HR 6.12 [95% CI 1.52–24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11–0.99] and HR 0.09 [95% CI 0.02–0.40], respectively). Conclusions: Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome. Keywords: Scedosporium spp., Lomentospora prolificans, Invasive fungal infections, Pediatric patients, Children, Voriconazole, Surgery, FungiScope® registry

Published
2020
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8. Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Author

Tamara Zoran, Bettina Sartori, Laura Sappl, Maria Aigner, Ferran Sánchez-Reus, Antonio Rezusta, Anuradha Chowdhary, Saad J. Taj-Aldeen, Maiken C. Arendrup, Salvatore Oliveri, Dimitrios P. Kontoyiannis, Ana Alastruey-Izquierdo, Katrien Lagrou, Giuliana Lo Cascio, Jacques F. Meis, Walter Buzina, Claudio Farina, Miranda Drogari-Apiranthitou, Anna Grancini, Anna M. Tortorano, Birgit Willinger, Axel Hamprecht, Elizabeth Johnson, Lena Klingspor, Valentina Arsic-Arsenijevic, Oliver A. Cornely, Joseph Meletiadis, Wolfgang Prammer, Vivian Tullio, Jörg-Janne Vehreschild, Laura Trovato, Russell E. Lewis, Esther Segal, Peter-Michael Rath, Petr Hamal, Manuel Rodriguez-Iglesias, Emmanuel Roilides, Sevtap Arikan-Akdagli, Arunaloke Chakrabarti, Arnaldo L. Colombo, Mariana S. Fernández, M. Teresa Martin-Gomez, Hamid Badali, Georgios Petrikkos, Nikolai Klimko, Sebastian M. Heimann, Omrum Uzun, Maryam Roudbary, Sonia de la Fuente, Jos Houbraken, Brigitte Risslegger, Raquel Sabino, Cornelia Lass-Flörl, and Michaela Lackner

Subjects
cryptic species, Aspergillus section Terrei, susceptibility profiles, azoles, Cyp51A alterations, Microbiology, QR1-502
Published
2019
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9. Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Author

Tamara Zoran, Bettina Sartori, Laura Sappl, Maria Aigner, Ferran Sánchez-Reus, Antonio Rezusta, Anuradha Chowdhary, Saad J. Taj-Aldeen, Maiken C. Arendrup, Salvatore Oliveri, Dimitrios P. Kontoyiannis, Ana Alastruey-Izquierdo, Katrien Lagrou, Giuliana Lo Cascio, Jacques F. Meis, Walter Buzina, Claudio Farina, Miranda Drogari-Apiranthitou, Anna Grancini, Anna M. Tortorano, Birgit Willinger, Axel Hamprecht, Elizabeth Johnson, Lena Klingspor, Valentina Arsic-Arsenijevic, Oliver A. Cornely, Joseph Meletiadis, Wolfgang Prammer, Vivian Tullio, Jörg-Janne Vehreschild, Laura Trovato, Russell E. Lewis, Esther Segal, Peter-Michael Rath, Petr Hamal, Manuel Rodriguez-Iglesias, Emmanuel Roilides, Sevtap Arikan-Akdagli, Arunaloke Chakrabarti, Arnaldo L. Colombo, Mariana S. Fernández, M. Teresa Martin-Gomez, Hamid Badali, Georgios Petrikkos, Nikolai Klimko, Sebastian M. Heimann, Omrum Uzun, Maryam Roudbary, Sonia de la Fuente, Jos Houbraken, Brigitte Risslegger, Cornelia Lass-Flörl, and Michaela Lackner

Subjects
cryptic species, Aspergillus section Terrei, susceptibility profiles, azoles, Cyp51A alterations, Microbiology, QR1-502
Abstract

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied.Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene.Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V.Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Published
2018
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10. An Estimate of Severe and Chronic Fungal Diseases in the Republic of Kazakhstan

Author

Vadim M. Kemaykin, Nariman B. Tabinbaev, Mahira S. Khudaibergenova, Anastasia A. Olifirovich, Layzzat M. Abdrakhmanova, David W. Denning, and Nikolai Klimko

Subjects
Leading International Fungal Education (LIFE) Program, mycoses, fungal diseases, Republic of Kazakhstan, Biology (General), QH301-705.5
Abstract

Our work aimed to generate a preliminary estimation of severe and chronic fungal diseases in the Republic of Kazakhstan with a model proposed by LIFE (Leading International Fungal Education). Calculations were carried out on data from 2015. Published results of studies of mycoses in Kazakhstan were identified; in the absence of national data from the scientific literature, the frequency of life-threatening and serious mycoses in defined groups of patients at risk from other countries were taken into account. We also used analogous estimations of mycoses in the Russian Federation. We estimate that 300,824 patients (1.7% of the population) were affected by severe and chronic mycotic diseases. There were an estimated 15,172 cases of acute mycoses, notably tinea capitis in children (11,847), Pneumocystis pneumonia and invasive candidiasis, and 285,652 of chronic fungal diseases. The most frequent were chronic recurrent vulvovaginal candidiasis (273,258 cases) and chronic pulmonary aspergillosis (6231). There is uncertainty about the prevalence of asthma in adults; the official number is 12,478 patients, but a prevalence estimate of 1.47% from a WHO consortium yields a prevalence of ~170,000 affected. We have used the official figures to generate the prevalence of fungal asthma, but it is likely to be a significant underestimate. Conclusion: Results of investigation indicate significant prevalence of severe and chronic mycoses in the Republic of Kazakhstan.

Published
2018
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11. COVID-19–associated mucormycosis: a systematic review and meta-analysis of 958 cases

Author

Laşin Özbek, Umur Topçu, Mehtap Manay, Buğra Han Esen, Sevval Nur Bektas, Serhat Aydın, Barış Özdemir, Sofya N. Khostelidi, Nikolai Klimko, Oliver Cornely, Johnny Zakhour, Souha S. Kanj, Danila Seidel, Martin Hoenigl, and Önder Ergönül

Subjects
Microbiology (medical), Infectious Diseases, General Medicine
Published
2023

12. COVID-19 and CAR T cells: a report on current challenges and future directions from the EPICOVIDEHA survey by EHA-IDWP

Author

Johan Maertens, Austin Kulesekararaj, Carolina Garcia-Vidal, Nina Khanna, Ildefonso Espigado, Alessandro Busca, Martin Hoenigl, Philipp Koehler, Anna Guidetti, Nikolai Klimko, Ramón García-Sanz, Josip Batinić, Alba Cabirta, Antonio Pagliuca, Rémy Duléry, Francesca Farina, Oliver A. Cornely, Jon Salmanton-García, Sylvain Lamure, Anna Nordlander, Francesco Passamonti, Lubos Drgona, Francesco Marchesi, Barbora Weinbergerova, Alberto Lopez-Garcia, Iker Falces-Romero, Livio Pagano, Paolo Corradini, Roberta Di Blasi, Institut Català de la Salut, [Busca A] Stem Cell Transplant Center, Azienda Ospedaliera Universitaria Città della Salute e della Scienza, Turin, Italy. [Salmanton-García J] Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), Faculty of Medicine and University Hospital Cologne, Cologne, Germany. Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital Cologne, Cologne, Germany. [Corradini P] University of Milan and Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan, Italy. [Marchesi F] Hematology and Stem Cell Transplant Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. [Cabirta A] Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain. [Di Blasi R] Hôpital Saint Louis, Assistance Publique–Hopitaux de Paris (AP-HP), Paris, France, and Vall d'Hebron Barcelona Hospital Campus

Subjects
medicine.medical_specialty, CAR-T cells, Coronavirus disease 2019 (COVID-19), T-Lymphocytes, medicine.medical_treatment, Adoptive, Psychological intervention, MEDLINE, registry, Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunization::Immunization, Passive::Adoptive Transfer::Immunotherapy, Adoptive [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], COVID-19 (Malaltia), Immunotherapy, Adoptive, terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunización::inmunización pasiva::transferencia adoptiva::inmunoterapia adoptiva [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Receptors, Case fatality rate, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Humans, Medicine, Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::Lymphocytes::T-Lymphocytes [ANATOMY], 030304 developmental biology, 0303 health sciences, Receptors, Chimeric Antigen, Hematology, business.industry, Prevention, Teràpia cel·lular, Risk of infection, Chimeric Antigen, COVID-19, Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], Immunosuppression, Stimulus Report, Chimeric antigen receptor, 3. Good health, Settore MED/15 - MALATTIE DEL SANGUE, Good Health and Well Being, Cèl·lules T, 030220 oncology & carcinogenesis, Immunotherapy, Infection, business, células::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::linfocitos T [ANATOMÍA]
Abstract

Patients receiving chimeric antigen receptor T cells (CAR-T cells) therapy may be particularly susceptible to coronavirus disease 2019 (COVID-19) because of several factors including the immunosuppression associated to the underlying disease and delayed cytopenias. Regrettably, data on outcomes of CAR-T recipients with COVID-19 are extremely scarce. The aim of this study was to investigate the characteristics and outcomes of COVID-19 in patients treated with CAR-T therapy. The European Hematology Association - Scientific Working Group Infection in Hematology endorsed a survey to collect and analyze data from patients developing COVID-19 after CAR-T therapy. Overall, 459 patients treated with CAR-T cells were reported from 18 European centers. The prevalence of COVID-19 cases was 4.8%. Median time from CAR-T therapy and COVID-19 diagnosis was 169 days. Severe infection occurred in 66.7% of patients and 43.3% of the subjects required admission to ICU. The COVID-19 mortality was 33%. In multivariable analysis, the disease status at the time of COVID-19 trended marginally towards adverse outcome (P=0.075). In conclusion, we documented a high fatality rate for CAR-T patients with COVID-19, supporting the need to design successful interventions to mitigate the risk of infection in this vulnerable group of patients.

Published
2022

13. Guideline adherence and survival of patients with candidaemia in Europe: results from the ECMM Candida III multinational European observational cohort study

Author

Martin Hoenigl, Jon Salmanton-García, Matthias Egger, Jean-Pierre Gangneux, Tihana Bicanic, Sevtap Arikan-Akdagli, Ana Alastruey-Izquierdo, Nikolai Klimko, Aleksandra Barac, Volkan Özenci, Eelco F J Meijer, Nina Khanna, Matteo Bassetti, Riina Rautemaa-Richardson, Katrien Lagrou, Kai-Manuel Adam, Emin Halis Akalin, Murat Akova, Valentina Arsic Arsenijevic, Avinash Aujayeb, Ola Blennow, Stéphane Bretagne, François Danion, Blandine Denis, Nick Alexander de Jonge, Guillaume Desoubeaux, Lubos Drgona, Nurettin Erben, Andrea Gori, Julio García Rodríguez, Carolina Garcia-Vidal, Daniele Roberto Giacobbe, Anna L Goodman, Petr Hamal, Helena Hammarström, Cristina Toscano, Fanny Lanternier, Cornelia Lass-Flörl, Deborah E A Lockhart, Thomas Longval, Laura Loughlin, Tadeja Matos, Malgorzata Mikulska, Manjusha Narayanan, Sonia Martín-Pérez, Juergen Prattes, Benedict Rogers, Laman Rahimli, Maite Ruiz, Emmanuel Roilides, Michael Samarkos, Ulrike Scharmann, Uluhan Sili, Oguz Resat Sipahi, Alena Sivakova, Joerg Steinmann, Janina Trauth, Ozge Turhan, Jens Van Praet, Antonio Vena, P Lewis White, Birgit Willinger, Anna Maria Tortorano, Maiken C Arendrup, Philipp Koehler, Oliver A Cornely, Mario Tumbarello, Alida Fe Talento, Alba C Ruiz, Zdenek Racil, Igor Stoma, Maria Calbacho, Eric Van Wijngaerden, Júlia Henriques, Harriett Jordan, Valentina Ferroni, Ozlem Koyuncu Ozyurt, Christopher Milacek, Robert Krause, Christoph Zurl, Matthijs Backx, Ang Li, Raphael Seufert, Rok Tomazin, Yael Blankenheim, Julio Dávila-Valls, Paloma García-Clemente, Tomas Freiberger, Jochem Buil, Jacques F Meis, Deniz Akyol, Hélène Guegan, Clare Logan, Medical University of Graz, University of Cologne, Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CHU Pontchaillou [Rennes], Scynexis, Hoenigl M., Salmanton-García J., Egger M., Gangneux J., Bicanic T., Arikan-Akdagli S., Alastruey-Izquierdo A., Klimko N., Barac A., Özenci V., et al., and Hematology

Subjects
MESH: Humans, İmmünoloji, Temel Bilimler, Settore MED/42 - Igiene Generale e Applicata, Medizin, Life Sciences, Life Sciences (LIFE), MESH: Adult, INFECTIOUS DISEASES, Sağlık Bilimleri, MESH: Antifungal Agents, MESH: Candidemia, IMMUNOLOGY, Bulaşıcı hastalıklar, Yaşam Bilimleri (LIFE), BULAŞICI HASTALIKLAR, MESH: Candida, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Yaşam Bilimleri, Health Sciences, MESH: Guideline Adherence, MESH: Europe, Natural Sciences, MESH: Cohort Studies
Abstract

Background: The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. Methods: In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. Findings: 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04–1·11; p

Published
2023

14. COVID-19 and Hairy-Cell Leukemia: An EPICOVIDEHA Survey

Author

Sylvain Lamure, Jon Salmanton-García, Elena Robin-Marieton, Ozren Jaksic, Milena Kohn, Francesco Marchesi, Monia Marchetti, Shaimaa El-Ashwah, Fatih Demirkan, Toni Valković, Noemí Fernández, Maria Chiara Tisi, Zlate Stojanoski, Guldane Cengiz Seval, Osman Ilhan, Lucia Prezioso, Maria Merelli, Alberto López-García, Marie-Pierre Ledoux, Austin Kulasekararaj, Tomás-José González-López, Maria Gomes da Silva, Ziad Emarah, Rafael F. Duarte, Chiara Cattaneo, Ola Blennow, Yavuz M. Bilgin, Rui Bergantim, Josip Batinić, Raul Cordoba, Jenna Essame, Anna Nordlander, Raquel Nunes Rodrigues, Maria Vittoria Sacchi, Sofia Zompi, Alessandro Busca, Paolo Corradini, Martin Hoenigl, Nikolai Klimko, Philipp Koehler, Antonio Pagliuca, Francesco Passamonti, Rémy Duléry, Oliver A. Cornely, Caroline Besson, and Livio Pagano

Subjects
BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, Leukemia, Hairy Cell, Leukemia, Hairy Cell, COVID19, hairy cell leukemia, COVID-19, Hematology, Hairy Cell Leukemia, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Infectology, Settore MED/15 - MALATTIE DEL SANGUE, Leukemia, Hairy Cell / epidemiology, Humans, Leukemia, Hairy Cell / complications, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Infektologija, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine
Abstract

not available

Published
2022

15. Invasive Scedosporium spp. and Lomentospora prolificans infections in pediatric patients: Analysis of 55 cases from FungiScope® and the literature

Author

Cornelia Lass-Flörl, Pere Soler-Palacín, Matthew P. Cheng, Hilmar Wisplinghoff, Alfredo Jover Sáenz, Zoi D Pana, Philipp Koehler, Angela Hassler, Iker Falces-Romero, Raoul Herbrecht, Fabianne Carlesse, Sibylle C. Mellinghoff, Jon Salmanton-García, Thomas Lehrnbecher, Nikolai Klimko, Danila Seidel, Oliver A. Cornely, and Mihai Mares

Subjects
Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Antifungal Agents, Adolescent, 030106 microbiology, LOMENTOSPORA PROLIFICANS, Clinical manifestation, Malignancy, lcsh:Infectious and parasitic diseases, Scedosporium, 03 medical and health sciences, 0302 clinical medicine, Risk groups, Risk Factors, Amphotericin B, Internal medicine, medicine, Humans, lcsh:RC109-216, ddc:610, 030212 general & internal medicine, Child, Voriconazole, business.industry, Infant, General Medicine, medicine.disease, Infectious Diseases, Mycoses, Child, Preschool, Female, business, Median survival, medicine.drug
Abstract

Objectives: Current knowledge on infections caused by Scedosporium spp. and Lomentospora prolificans in children is scarce. We therefore aim to provide an overview of risk groups, clinical manifestation and treatment strategies of these infections. Methods: Pediatric patients (age ≤18 years) with proven/probable Scedosporium spp. or L. prolificans infection were identified in PubMed and the FungiScope® registry. Data on diagnosis, treatment and outcome were collected. Results: Fifty-five children (median age 9 years [IQR: 5–14]) with invasive Scedosporium spp. (n = 33) or L. prolificans (n = 22) infection were identified between 1990 and 2019. Malignancy, trauma and near drowning were the most common risk factors. Infections were frequently disseminated. Most patients received systemic antifungal therapy, mainly voriconazole and amphotericin B, plus surgical treatment.Overall, day 42 mortality was 31%, higher for L. prolificans (50%) compared to Scedosporium spp. (18%). L. prolificans infection was associated with a shorter median survival time compared to Scedosporium spp. (6 days [IQR: 3–28] versus 61 days [IQR: 16–148]). Treatment for malignancy and severe disseminated infection were associated with particularly poor outcome (HR 8.33 [95% CI 1.35–51.40] and HR 6.12 [95% CI 1.52–24.66], respectively). Voriconazole use at any time and surgery for antifungal treatment were associated with improved clinical outcome (HR 0.33 [95% CI 0.11–0.99] and HR 0.09 [95% CI 0.02–0.40], respectively). Conclusions: Scedosporium spp. and L. prolificans infections in children are associated with high mortality despite comprehensive antifungal therapy. Voriconazole usage and surgical intervention are associated with successful outcome. Keywords: Scedosporium spp., Lomentospora prolificans, Invasive fungal infections, Pediatric patients, Children, Voriconazole, Surgery, FungiScope® registry

Published
2020

16. The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries

Author

Martin Hoenigl, Danila Seidel, Agostinho Carvalho, Shivaprakash M Rudramurthy, Amir Arastehfar, Jean-Pierre Gangneux, Nosheen Nasir, Alexandro Bonifaz, Javier Araiza, Nikolai Klimko, Alexandra Serris, Katrien Lagrou, Jacques F Meis, Oliver A Cornely, John R Perfect, P Lewis White, Arunaloke Chakrabarti, Jonchère, Laurent, Medical University of Graz, University of California [San Diego] (UC San Diego), University of California (UC), University of Cologne, Universidade do Minho = University of Minho [Braga], Post Graduate Institute of Medical Education and Research [Chandigarh, India] (PGIMER), Center for Discovery and Innovation - Hackensack Meridian Health (CDI), Hackensack Meridian Health, CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), The Aga Khan University, Hospital General de México Dr. Eduardo Liceaga (HGM), North-Western State Medical University [St Petersburg, Russia], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), University Hospitals Leuven [Leuven], Radboud University Medical Center [Nijmegen], Canisius-Wilhelmina Hospital [Nijmegen, The Netherlands], Duke University Medical Center, University Hospital of Wales (UHW), National Institutes of Health, NIH: UL1TR001442, Pfizer, Astellas Pharma US, APUS: ISR005824, ISR005838, Gilead Sciences, Meso Scale Diagnostics, MSD, 'la Caixa' Foundation: 100010434, LCF/PR/HR17/52190003, Fundação para a Ciência e a Tecnologia, FCT: UIDB/50026/2020, UIDP/50026/2020, and European Regional Development Fund, ERDF: NORTE-01-0145-FEDER-000039

Subjects
Microbiology (medical), SARS-CoV-2, [SDV]Life Sciences [q-bio], COVID-19, Review, Microbiology, [SDV] Life Sciences [q-bio], Infectious Diseases, Risk Factors, Virology, Diabetes Mellitus, Humans, Mucormycosis, RNA, Viral, ECMM and ISHAM collaborators
Abstract

International audience; Reports of COVID-19-associated mucormycosis have been increasing in frequency since early 2021, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycaemia often have an inflammatory state that could be potentiated by the activation of antiviral immunity to SARS-CoV2, which might favour secondary infections. In this Review, we analysed 80 published and unpublished cases of COVID-19-associated mucormycosis. Uncontrolled diabetes, as well as systemic corticosteroid treatment, were present in most patients with COVID-19-associated mucormycosis, and rhino-orbital cerebral mucormycosis was the most frequent disease. Mortality was high at 49%, which was particularly due to patients with pulmonary or disseminated mucormycosis or cerebral involvement. Furthermore, a substantial proportion of patients who survived had life-changing morbidities (eg, loss of vision in 46% of survivors). Our Review indicates that COVID-19-associated mucormycosis is associated with high morbidity and mortality. Diagnosis of pulmonary mucormycosis is particularly challenging, and might be frequently missed in India. © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license

Published
2022

17. Guideline Adherence Predicts Survival of Candidemia in Europe: Results from the ECMM Candida III Multinational European Study

Author

Martin Hoenigl, Jon Salmanton-Garcia, Matthias Egger, Jean-Pierre Gangneux, Tihana Bicanic, Sevtap Arikan-Akdagli, Ana Alastruey-Izquierdo, Nikolai Klimko, Aleksandra Barac, Volkan Özenci, Eelco F. J. Meijer, Nina Khanna, Matteo Bassetti, Riina Rautemaa-Richardson, Katrien Lagrou, Kai-Manuel Adam, Emin Halis Akalın, Murat Akova, Valentina Arsic-Arsenijevic, Avinash Aujayeb, Ola Blennow, Stephane Bretagne, François Danion, Blandine Denis, Nick Alexander de Jonge, Guillaume Desoubeaux, Lubos Drgona, Nurettin Erben, Andrea Gori, Julio García Rodríguez, Carolina Garcia-Vidal, Daniele Roberto Giacobbe, Anna L. Goodman, Petr Hamal, Helena Hammarström, Christina Toscano, Fanny Lanternier, Cornelia Lass-Flörl, Deborah E. A. Lockhart, Thomas Longval, Laura Loughlin, Tadeja Matos, Malgorzata Mikulska, Manjusha Narayanan, Sonia Martín-Pérez, Juergen Prattes, Benedict Rogers, Laman Rahimli, Maite Ruiz, Emmanuel Roilides, Michael Samarkos, Ulrike Scharmann, Uluhan Sili, Oguz Resat Sipahi, Alena Siváková, Joerg Steinmann, Janina Trauth, Özge Turhan, Jens Van Praet, Antonio Vena, Lewis White, Birgit Willinger, Anna Maria Tortorano, Maiken C. Arendrup, Philipp Koehler, Oliver A. Cornely, and ECMM Candida III Study Group

Published
2022

18. EPICOVIDEHA: A Ready to Use Platform for Epidemiological Studies in Hematological Patients With COVID-19

Author

Livio Pagano, Philipp Koehler, Alessandro Busca, Paolo Corradini, Jon Salmanton-García, Oliver A. Cornely, Francesco Marchesi, Nikolai Klimko, Martin Hoenigl, Francesco Passamonti, and Antonio Pagliuca

Subjects
2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), MEDLINE, leukemia, Hematology, Settore MED/15 - MALATTIE DEL SANGUE, Editorial, Epidemiology, medicine, Ready to use, Diseases of the blood and blood-forming organs, RC633-647.5, business, Intensive care medicine, Infection
Published
2021

19. Global guideline for the diagnosis and management of the endemic mycoses: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology

Author

Peter-Michael Rath, Methee Chayakulkeeree, Alessandro C. Pasqualotto, Christopher C. Kibbler, María José Buitrago, Thuy Le, Neil M Ampel, Flavio Queiroz-Telles, Ferry Hagen, Oliver A. Cornely, Paul E. Verweij, Ana Alastruey-Izquierdo, Ariya Chindamporn, Nelesh P. Govender, Carol A. Kauffman, Graeme Meintjes, Darius Armstrong-James, Chris Kenyon, Grégory Jouvion, Ilan S. Schwartz, Olusola Ayanlowo, Jean-Pierre Gangneux, John W Baddley, George Richard Thompson, Jasper Fuk-Woo Chan, David R. Andes, Tobias M. Hohl, Low Lee Lee, Andrej Spec, Cao Cun-wei, Robert Krause, Ebrahim Variava, Marisa H. Miceli, David C M Kong, Leili Chamani-Tabriz, Mohammad Taghi Hedayati, Bridget M. Barker, Nikolai Klimko, Leila Maria Lopes Bezerra, University of California [Davis] (UC Davis), University of California, Duke University [Durham], Chulalongkorn University [Bangkok], University of Michigan Medical School [Ann Arbor], University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Instituto de Salud Carlos III [Madrid] (ISC), University of Arizona, University of Wisconsin-Madison, Imperial College London, University of Lagos, University of Maryland School of Medicine, University of Maryland System, The Pathogen and Microbiome Institute, Northern Arizona University [Flagstaff], State University of Rio de Janeiro, The University of Hong Kong (HKU), Mahidol University [Bangkok], University Hospital of Cologne [Cologne], Guangxi University [Nanning], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), National Institute for Communicable Diseases [Johannesburg] (NICD), University of the Witwatersrand [Johannesburg] (WITS), University Medical Center [Utrecht], Mazandaran University of Medical Sciences, Memorial Sloan Kettering Cancer Center (MSKCC), Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris]-Université de Paris (UP), Maladies génétiques d'expression pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Tropical Medicine [Antwerp] (ITM), University College of London [London] (UCL), University of Ballarat [Australie] (FedUni), Institute of Biophysics [Graz], Medical University Graz, University of Cape Town, Ruhrlandklinik University Hospital, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Federal University of Technology - Paraná (UTFPR), Radboud University Medical Center [Nijmegen], University of Alberta, Federal University of Health Sciences of Porto Alegre = Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), University of California (UC), 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 ), Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Maladies génétiques d'expression pédiatrique (U933), and Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP]

Subjects
medicine.medical_specialty, Consensus, Endemic Diseases, [SDV]Life Sciences [q-bio], International Cooperation, Clinical Sciences, Clinical Decision-Making, Medizin, MEDLINE, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Guidelines as Topic, Global Health, Microbiology, Article, Histoplasmosis, Vaccine Related, 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Risk Factors, Biodefense, Mycology, Epidemiology, medicine, Animals, Humans, 030212 general & internal medicine, Intensive care medicine, 0303 health sciences, Sporotrichosis, 030306 microbiology, Paracoccidioidomycosis, business.industry, Prevention, Guideline, medicine.disease, 3. Good health, Europe, Emerging Infectious Diseases, Good Health and Well Being, Infectious Diseases, Mycoses, Medical Microbiology, Public Health and Health Services, Infection, business, Blastomycosis
Abstract

International audience; The global burden of the endemic mycoses (blastomycosis, coccidioidomycosis, emergomycosis, histoplasmosis, paracoccidioidomycosis, sporotrichosis, and talaromycosis) continues to rise yearly and these infectious diseases remain a leading cause of patient morbidity and mortality worldwide. Management of the associated pathogens requires a thorough understanding of the epidemiology, risk factors, diagnostic methods and performance characteristics in different patient populations, and treatment options unique to each infection. Guidance on the management of these infections has the potential to improve prognosis. The recommendations outlined in this Review are part of the "One World, One Guideline" initiative of the European Confederation of Medical Mycology. Experts from 23 countries contributed to the development of these guidelines. The aim of this Review is to provide an up-to-date consensus and practical guidance in clinical decision making, by engaging physicians and scientists involved in various aspects of clinical management.

Published
2021

20. The Emergence of COVID-19 Associated Mucormycosis: Analysis of Cases From 18 Countries

Author

Martin Hoenigl, Danila Seidel, Agostinho Carvalho, Shivaprakash M. Rudramurthy, Amir Arastehfar, Jean Pierre Gangneux, Nosheen Nasir, Alexandro Bonifaz, Javier Araiza, Nikolai Klimko, Alexandra Serris, Katrien Lagrou, Jacques F. Meis, Oliver A. Cornely, John R. Perfect, P. Lewis White, Arunaloke Chakrabarti, and ECMM and ISHAM Collaborators Group

Subjects
medicine.medical_specialty, business.operation, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Secondary infection, Mucormycosis, Declaration, medicine.disease, Octapharma, Family medicine, Honorarium, medicine, media_common.cataloged_instance, European union, business, media_common
Abstract

Coronavirus disease 2019 (COVID-19)–associated mucormycosis (CAM) has recently been increasingly reported, particularly among patients with uncontrolled diabetes. Patients with diabetes and hyperglycemia often display an inflammatory state that may be potentiated by the activation of antiviral immunity to SARS-CoV-2, and thus may favor secondary infections. We analyze 80 published and unpublished cases of CAM, with a predominance (42/80) of cases from India. Uncontrolled diabetes mellitus as well as systemic corticosteroid treatment represented major comorbid predisposing factors and rhino-orbital cerebral mucormycosis was the most frequent presentation of disease. Mortality was high at 49%, driven particularly by those with pulmonary or disseminated mucormycosis and those with cerebral involvement. Furthermore, a significant proportion of surviving patients suffered life-changing morbidities (loss of vision in 46% of survivors). Our review indicates that CAM may be a relevant complication of severe COVID-19, particularly in those with uncontrolled diabetes. Funding: Martin Hoenigl received funding from Astellas for two investigator initiated studies (ISR005824 and ISR005838), and was supported by the National Institutes of Health, Grant UL1TR001442. Agostinho Carvalho was supported by the Fundacao para a Ciencia e a Tecnologia (FCT) (UIDB/50026/2020 and UIDP/50026/2020), the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (NORTE-01-0145-FEDER-000039), the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 847507, and the “la Caixa” Foundation (ID 100010434) and FCT under the agreement LCF/PR/HR17/52190003. Declaration of Interest: MH received research funding from Gilead, Pfizer, Astellas, Scynexis and NIH. JPG received speaker and expert advice fees from Pfizer and Gilead. NK has received research grants or honoraria as a speaker or advisor from Astellas, Gilead, MSD, and Pfizer, outside the submitted work. KL received consultancy fees from SMB Laboratoires Brussels, MSD and Gilead, travel support from Pfizer, speaker fees from FUJIFILM WAKO, Pfizer and Gilead, a service fee from Thermo fisher Scientific. OAC is supported by the German Federal Ministry of Research and Education, is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy – CECAD, EXC 2030 – 390661388 and has received research grants from, is an advisor to, or received lecture honoraria from Actelion, Allecra Therapeutics, Al-Jazeera Pharmaceuticals, Amplyx, Astellas, Basilea, Biosys, Cidara, Da Volterra, Entasis, F2G, Gilead, Grupo Biotoscana, Immunic, IQVIA, Janssen, Matinas, Medicines Company, MedPace, Melinta Therapeutics, Menarini, Merck/MSD, Mylan, Nabriva, Noxxon, Octapharma, Paratek, Pfizer, PSI, Roche Diagnostics, Scynexis, and Shionogi. PLW performed diagnostic evaluations and received meeting sponsorship from Bruker, Dynamiker, and Launch Diagnostics; Speakers fees, expert advice fees and meeting sponsorship from Gilead; and speaker and expert advice fees 489 from F2G and speaker fees MSD and Pfizer. Is a founding member of the European Aspergillus PCR Initiative. ACh received funding support from educational grant of Pfizer, MSD Pharmaceutical Ltd, and Gilead. All other authors no conflicts. Ethical Approval: MISSING

Published
2021

21. Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScopeⓇ—Global Registry for Emerging Fungal Infections

Author

Shruti Malik, Barbara Graf, Anupma Jyoti Kindo, Michele I. Morris, Carol A. Kauffman, Hamid Badali, Frédéric Janvier, Barbara D. Alexander, Lóránt Hatvani, Iker Falces-Romero, George Richard Thompson, Thomas P. Weber, Aamer Ikram, Georg Haerter, Mathias W. Pletz, Arunaloke Chakrabarti, Monica A. Slavin, Alessandro C. Pasqualotto, María Almagro-Molto, Sibylle C. Mellinghoff, Martha Avilés-Robles, Michaela Lackner, Mario Fernández-Ruiz, Melina Heinemann, Miguel Ángel Benítez-Peñuela, Lisa Meintker, Aleksandra Barac, Olaf Penack, Diana L. Pakstis, Zdeněk Ráčil, Nicolas Pichon, John W. Baddley, Jin Yu, Raoul Herbrecht, Martin Hoenigl, Jesús García-Martínez, Paul R. Ingram, Robert Krause, Cornelia Lass-Flörl, Shariq Haider, Barbora Weinbergerova, Carlos Seas, Jeffrey D. Jenks, Simone Cesaro, Vanda Chrenková, Luis Figueira, Donald C. Sheppard, Guillaume Desoubeaux, Galina Klyasova, Seda Yilmaz-Semerci, Vincent Marconi, Gloria M. González, Philipp Koehler, Donald C. Vinh, Eduardo Álvarez-Duarte, Atul Patel, Damien Dupont, José Yesid Rodríguez, Kenji Uno, Sanjay Mehta, Nicole Desbois-Nogard, Sandra Gräber, Jagdish Chander, Rodrigo Martino, Kathleen M. Mullane, Andrea Mocná, Yohann Le Govic, Mihai Mareș, Hilmar Wisplinghoff, Serkan Atıcı, Patricia Cornejo-Juárez, Jose A. Vazquez, Uluhan Sili, Jon Salmanton-García, Oliver A. Cornely, Nikolai Klimko, Sharon C.-A. Chen, Danila Seidel, Pamela Hartman, Me Linh Luong, Julio García-Rodríguez, Deniz Yilmaz-Karapinar, Groupe d'Étude des Interactions Hôte-Pathogène (GEIHP), and Université d'Angers (UA)

Subjects
0301 basic medicine, Microbiology (medical), Mucorales, Fusariosis, medicine.medical_specialty, [SDV]Life Sciences [q-bio], 030106 microbiology, Eurotiales, yeast, invasive fungal infection, Malignancy, 03 medical and health sciences, 0302 clinical medicine, Epidemiology, medicine, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, invasive fungal infection, mold, yeast, Acute leukemia, biology, business.industry, Mortality rate, mold, Mucormycosis, medicine.disease, biology.organism_classification, Dermatology, 3. Good health, Infectious Diseases, business
Abstract

Objectives Emerging invasive fungal infections (IFI) have become a notable challenge. Apart from the more frequently described fusariosis, lomentosporiosis, mucormycosis, scedosporiosis, and certain dematiaceae or yeasts, little is known about extremely rare IFI. Methods Extremely rare IFI collected in the FungiScopeⓇ registry were grouped as Dematiaceae, Hypocreales, Saccharomycetales, Eurotiales, Dermatomycetes, Agaricales, and Mucorales. Results Between 2003 and June 2019, 186 extremely rare IFI were documented in FungiScopeⓇ. Dematiaceae (35.5%), Hypocreales (23.1%), Mucorales (11.8%), and Saccharomycetales (11.3%) caused most IFI. Most patients had an underlying malignancy (38.7%) with acute leukemia accounting for 50% of cancers. Dissemination was observed in 26.9% of the patients. Complete or partial clinical response rate was 68.3%, being highest in Eurotiales (82.4%) and in Agaricales (80.0%). Overall mortality rate was 29.3%, ranging from 11.8% in Eurotiales to 50.0% in Mucorales. Conclusions Physicians are confronted with a complex variety of fungal pathogens, for which treatment recommendations are lacking and successful outcome might be incidental. Through an international consortium of physicians and scientists, these cases of extremely rare IFI can be collected to further investigate their epidemiology and eventually identify effective treatment regimens.

Published
2020

23. Characterization and outcome of invasive infections due to Paecilomyces variotii: analysis of patients from the FungiScope® registry and literature reports

Author

Malik Shruti, Danila Seidel, Jon Salmanton-García, Rosanne Sprute, Xhorxha Malaj, Oliver A. Cornely, Joseph Meletiadis, Lóránt Hatvani, Joerg Steinmann, Ertan Sal, Melina Heinemann, Jannik Stemler, Leyre López-Soria, Iker Falces-Romero, and Nikolai Klimko

Subjects
Microbiology (medical), Posaconazole, medicine.medical_specialty, Antifungal Agents, Itraconazole, medicine.medical_treatment, Byssochlamys, Peritoneal dialysis, Flucytosine, Amphotericin B, Internal medicine, medicine, Humans, AcademicSubjects/MED00740, Pharmacology (medical), Registries, Original Research, Pharmacology, Voriconazole, biology, business.industry, Breakthrough infection, biology.organism_classification, Paecilomyces variotii, Infectious Diseases, AcademicSubjects/MED00290, Mycoses, business, Paecilomyces, AcademicSubjects/MED00230, medicine.drug
Abstract

Objectives To provide a basis for clinical management decisions in Paecilomyces variotii infection. Methods Unpublished cases of invasive P. variotii infection from the FungiScope® registry and all cases reported in the literature were analysed. Results We identified 59 cases with P. variotii infection. Main baseline factors were presence of indwelling devices in 29 cases (49.2%), particularly peritoneal catheters (33.9%) and prosthetic heart valves (10.2%), haematological or oncological diseases in 19 (32.2%), major surgery in 11 (18.6%), and diabetes mellitus in 10 cases (16.9%). The most prevalent infection sites were peritoneum (n = 20, 33.3%) and lungs (n = 16, 27.1%). Pain and fever were frequent (n = 35, 59.3% and n = 33, 55.9%, respectively). Diagnosis was established by culture in 58 cases (98.3%). P. variotii caused breakthrough infection in 8 patients. Systemic antifungals were given in 52 patients (88.1%). Amphotericin B was administered in 39, itraconazole in 15, and posaconazole in 8 patients. Clinical isolates were frequently resistant to voriconazole, whereas the above-mentioned antifungals showed good in vitro activity. Infections of the blood and CNS caused high mortality. Overall mortality was 28.8% and death was attributed to P. variotii in 10 cases. Conclusions P. variotii causes life-threatening infections, especially in immunocompromised and critically ill patients with indwelling devices. Patients undergoing peritoneal dialysis are at particular risk. Multidisciplinary management is paramount, including molecular techniques for diagnosis and treatment with efficacious systemic antifungals. Amphotericin B, itraconazole and posaconazole are regarded as treatments of choice. Combination with flucytosine may be considered. Surgical debridement and removal of indwelling devices facilitate favourable outcome.

Published
2020

24. Needles in a haystack: Extremely rare invasive fungal infections reported in FungiScope

Author

Jon, Salmanton-García, Philipp, Koehler, Anupma, Kindo, Iker, Falces-Romero, Julio, García-Rodríguez, Zdeněk, Ráčil, Sharon C-A, Chen, Nikolai, Klimko, Guillaume, Desoubeaux, George R, Thompson, Miguel-Ángel, Benítez-Peñuela, José-Yesid, Rodríguez, Donald C, Sheppard, Martin, Hoenigl, Yohann, Le Govic, Hamid, Badali, John W, Baddley, Jagdish, Chander, Paul R, Ingram, Diana L, Pakstis, Sibylle C, Mellinghoff, Serkan, Atıcı, Simone, Cesaro, Arunaloke, Chakrabarti, Damien, Dupont, Gloria M, González, Lóránt, Hatvani, Raoul, Herbrecht, Galina, Klyasova, Cornelia, Lass-Flörl, Mihai, Mareș, Kathleen, Mullane, Donald C, Vinh, Hilmar, Wisplinghoff, Michaela, Lackner, Oliver A, Cornely, Danila, Seidel, and Jin, Yu

Subjects
Antifungal Agents, Mycoses, Humans, Registries, Invasive Fungal Infections
Abstract

Emerging invasive fungal infections (IFI) have become a notable challenge. Apart from the more frequently described fusariosis, lomentosporiosis, mucormycosis, scedosporiosis, and certain dematiaceae or yeasts, little is known about extremely rare IFI.Extremely rare IFI collected in the FungiScopeBetween 2003 and June 2019, 186 extremely rare IFI were documented in FungiScopePhysicians are confronted with a complex variety of fungal pathogens, for which treatment recommendations are lacking and successful outcome might be incidental. Through an international consortium of physicians and scientists, these cases of extremely rare IFI can be collected to further investigate their epidemiology and eventually identify effective treatment regimens.

Published
2020

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

Author

Eléna Charpentier, Frédéric Gabriel, Frédéric Lamoth, Maria Aigner, Emmanouil Glampedakis, Michela Paolucci, Felix Bongomin, Malcolm Richardson, C. Bonnal, Russel Edward Lewis, Arnaud Fekkar, Christophe Hennequin, Stéphane Bretagne, Patrice Le Pape, Arnaud Riat, Reinhard Zbinden, Veronique Erard, Pierre-Yves Bochud, Marie-Elisabeth Bougnoux, Ahmet Çağkan İnkaya, Olga V Shadrivova, Sophie Brun, Nina Khanna, Dionysios Neofytos, Anne-Pauline Bellanger, Eric Dannaoui, Florent Morio, Peter W Schreiber, Sevtap Arikan-Akdagli, Mario Fernández-Ruiz, Alix T. Coste, Nikolai Klimko, Sophie Cassaing, Glampedakis E., Cassaing S., Fekkar A., Dannaoui E., Bougnoux M.-E., Bretagne S., Neofytos D., Schreiber P.W., Hennequin C., Morio F., Shadrivova O., Bongomin F., Fernandez-Ruiz M., Bellanger A.P., Arikan-Akdagli S., Erard V., Aigner M., Paolucci M., Khanna N., Charpentier E., Bonnal C., Brun S., Gabriel F., Riat A., Zbinden R., Le Pape P., Klimko N., Lewis R.E., Richardson M., Inkaya A.C., Coste A.T., Bochud P.-Y., Lamoth F., Hôpital Lausanne, Service de Parasitologie et Mycologie, CHU Toulouse [Toulouse]-Institut Fédératif de Biologie (IFB) - Hôpital Purpan, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Service de parasitologie - mycologie [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Unité de Parasitologie-Mycologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Parasitologie-Mycologie [CHU Saint Louis, Paris], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Hop Univ Geneve, Serv Malad Infect, Geneva, Switzerland, Department of Infectious Diseases and Hospital Epidemiology [Zurich], University hospital of Zurich [Zurich], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Laboratoire de Parasitologie-Mycologie (Institut de biologie, CHU de Nantes), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Saint-Petersburg, University of Manchester [Manchester], Unit Infectious Diseases, Hospital 12 de Octubre, Service de parasitologie et mycologie [CHRU de Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Ankara University School of Medicine [Turkey], University of Fribourg, Universität Innsbruck [Innsbruck], Department of Hematology and Oncology 'L. e A. Seragnoli', St. Orsola University Hospital, University Hospital Basel [Basel], Service de Parasitologie Mycologie[Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Parasitologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, CHU Bordeaux [Bordeaux], Hôpitaux Universitaire de Genève, Laboratoire de parasitologie et de mycologie médicale [CHU Nantes], Radiopharmaceutiques biocliniques (LRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, and Université de Lausanne (UNIL)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Posaconazole, Antifungal Agents, Aspergillosi, Aspergillus puniceus, 030106 microbiology, Aspergillus calidoustus, Aspergillus pseudodeflectus, Aspergillosis, 03 medical and health sciences, Aspergillus ustus, Retrospective Studie, Internal medicine, Amphotericin B, medicine, Antifungal Agent, Humans, Retrospective Studies, Voriconazole, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, ddc:616, business.industry, Mortality rate, Retrospective cohort study, Aspergillus insuetus, medicine.disease, Aspergillu, 3. Good health, 030104 developmental biology, Infectious Diseases, Aspergillus, business, Invasive Fungal Infections, medicine.drug, Human
Abstract

Background Aspergillus spp. of section Usti (A. ustus) represent a rare cause of invasive aspergillosis (IA). This multicenter study describes the epidemiology and outcome of A. ustus infections. Methods Patients with A. ustus isolated from any clinical specimen were retrospectively identified in 22 hospitals from 8 countries. When available, isolates were sent for species identification (BenA/CaM sequencing) and antifungal susceptibility testing. Additional cases were identified by review of the literature. Cases were classified as proven/probable IA or no infection, according to standard international criteria. Results Clinical report forms were obtained for 90 patients, of whom 27 had proven/probable IA. An additional 45 cases were identified from literature review for a total of 72 cases of proven/probable IA. Hematopoietic cell and solid-organ transplant recipients accounted for 47% and 33% cases, respectively. Only 8% patients were neutropenic at time of diagnosis. Ongoing antimold prophylaxis was present in 47% of cases. Pulmonary IA represented 67% of cases. Primary or secondary extrapulmonary sites of infection were observed in 46% of cases, with skin being affected in 28% of cases. Multiple antifungal drugs were used (consecutively or in combination) in 67% of cases. The 24-week mortality rate was 58%. A. calidoustus was the most frequent causal agent. Minimal inhibitory concentrations encompassing 90% isolates (MIC90) were 1, 8, >16, and 4 µg/mL for amphotericin B, voriconazole, posaconazole, and isavuconazole, respectively. Conclusions Aspergillus ustus IA mainly occurred in nonneutropenic transplant patients and was frequently associated with extrapulmonary sites of infection. Mortality rate was high and optimal antifungal therapy remains to be defined.

Published
2019

26. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis

Author

Ilana Oren, Jo Anne H. Young, Ploenchan Chetchotisakd, George J Alangaden, Sameer R. Melinkeri, John R. Perfect, Sutep Jaruratanasirikul, Jörg Janne Vehreschild, Janice M. Brown, Zdeněk Ráčil, Johan Maertens, Oliver A. Cornely, Raoul Herbrecht, Masanori Ito, Peter G. Pappas, Rodrigo Ribeiro dos Santos, Souha S. Kanj, Bernhardt Zeiher, Rochelle Maher, Maria J G T Vehreschild, Luis Ostrosky-Zeichner, Francisco M. Marty, Nikolai Klimko, Galia Rahav, Stefan Schwartz, David N. Fredricks, Marc Engelhardt, Werner J. Heinz, George Richard Thompson, Kathleen M. Mullane, Carolyn Sasse, Achim Kaufhold, Galina Klyasova, and Misun Lee

Subjects
Adult, Male, 0301 basic medicine, medicine.medical_specialty, Posaconazole, Antifungal Agents, Pyridines, 030106 microbiology, Aspergillosis, 03 medical and health sciences, Amphotericin B, Internal medicine, Nitriles, Animals, Humans, Mucormycosis, Medicine, Voriconazole, business.industry, Fungi, Middle Aged, Triazoles, medicine.disease, Isavuconazonium, 3. Good health, Surgery, Treatment Outcome, Infectious Diseases, Administration, Intravenous, Female, Zygomycosis, business, Progressive disease, medicine.drug
Abstract

Summary Background Mucormycosis is an uncommon invasive fungal disease with high mortality and few treatment options. Isavuconazole is a triazole active in vitro and in animal models against moulds of the order Mucorales. We assessed the efficacy and safety of isavuconazole for treatment of mucormycosis and compared its efficacy with amphotericin B in a matched case-control analysis. Methods In a single-arm open-label trial (VITAL study), adult patients (≥18 years) with invasive fungal disease caused by rare fungi, including mucormycosis, were recruited from 34 centres worldwide. Patients were given isavuconazole 200 mg (as its intravenous or oral water-soluble prodrug, isavuconazonium sulfate) three times daily for six doses, followed by 200 mg/day until invasive fungal disease resolution, failure, or for 180 days or more. The primary endpoint was independent data review committee-determined overall response—ie, complete or partial response (treatment success) or stable or progressive disease (treatment failure)—according to prespecified criteria. Mucormycosis cases treated with isavuconazole as primary treatment were matched with controls from the FungiScope Registry, recruited from 17 centres worldwide, who received primary amphotericin B-based treatment, and were analysed for day-42 all-cause mortality. VITAL is registered with ClinicalTrials.gov, number NCT00634049. FungiScope is registered with ClinicalTrials.gov, number NCT01731353. Findings Within the VITAL study, from April 22, 2008, to June 21, 2013, 37 patients with mucormycosis received isavuconazole for a median of 84 days (IQR 19–179, range 2–882). By day 42, four patients (11%) had a partial response, 16 (43%) had stable invasive fungal disease, one (3%) had invasive fungal disease progression, three (8%) had missing assessments, and 13 (35%) had died. 35 patients (95%) had adverse events (28 [76%] serious). Day-42 crude all-cause mortality in seven (33%) of 21 primary-treatment isavuconazole cases was similar to 13 (39%) of 33 amphotericin B-treated matched controls (weighted all-cause mortality: 33% vs 41%; p=0·595). Interpretation Isavuconazole showed activity against mucormycosis with efficacy similar to amphotericin B. Isavuconazole can be used for treatment of mucormycosis and is well tolerated. Funding Astellas Pharma Global Development, Basilea Pharmaceutica International.

Published
2016

27. 2268. Clinical Implications of Azole-Resistant vs. Azole-Susceptible Invasive Aspergillosis in Hematological Malignancy (CLARITY): A Multicenter Study

Author

Jörg Steinmann, Agustin Resendiz Sharpe, Danila Seidel, Katrien Lagrou, Anne Bergeron-Lafaurie, Jörg J. Vehreschild, Jürgen Prattes, Jon Salmanton-García, Alen Ostojić, Paul E. Verweij, Enrico Schalk, Maria J G T Vehreschild, Marouan Zarrouk, Dorothee Arenz, Yohann Legovic, Johan Maertens, Iker Falces Romero, Nikolai Klimko, Willem J. G. Melchers, Nael Alakel, Cornelia Lass-Flörl, Ola Blennow, Oliver A. Cornely, Marta Stanzani, Guillaume Desoubeaux, Jacques F. Meis, Zdenek Racil, and Dieter Buchheidt

Subjects
chemistry.chemical_classification, Aspergillus, biology, business.industry, Hematologic Neoplasms, biology.organism_classification, Aspergillosis, medicine.disease, Pathogenicity, 3. Good health, Aspergillus fumigatus, Abstracts, Infectious Diseases, Oncology, Multicenter study, chemistry, Hematological malignancy, Poster Abstracts, Immunology, medicine, Azole, business
Abstract

Background In recent years, survival of patients with invasive aspergillosis (IA) has improved mainly due to availability of extended spectrum triazoles. These advances are jeopardized by the emergence of azole resistance in Aspergillus fumigatus, the most common causative pathogen of IA. Despite several studies suggesting high probability of azole treatment failure in patients with azole-resistant isolates, the clinical implications of azole-resistant IA compared with azole-susceptible IA remain unclear. Methods In patients with hematological malignancies, cases of proven or probable IA (EORTC/MSG 2008) caused by A. fumigatus are registered. Retrospective data are documented, comprising demographics, diagnosis, treatment, response and outcome. Participating sites provided susceptibility results or isolates. Provided isolates were analyzed in a central laboratory. Results Since January 2018, 51 sites in 15 countries worldwide enrolled 154 cases diagnosed with IA between 2010 and 2019, of which 23 (14.9%) had azole-resistant IA. Of 44 cases, the respective clinical fungal isolate was analyzed in the central laboratory. A mixed fungal infection was reported for 34 patients (22.1%), 1 (2.9%) in the azole-resistant group; most were related to non-fumigatus Aspergillus species (n = 12, 35.3%) and non-Aspergillus molds (n = 10, 29.4). Most patients were male (n = 98, 63.6%); 19 (82.6%) in the azole-resistant group, 79 (60.3%) in the azole-susceptible group. Age was documented in categories instead of the exact age. Median age group was 50–69 years in both groups (ranging from 7–11 to 70–89 years for azole-resistant cases, 1–12 months to 70–89 years for azole-susceptible cases). Underlying disease and survival are shown in the table. Conclusion A worldwide network of investigators contributes to the CLARITY registry study. Completion of recruitment and subsequent data analysis are planned for 2019. Further sites may be added if azole-resistant cases are encountered. Disclosures All authors: No reported disclosures.

Published
2019

28. PS1276 EPIDEMIOLOGY AND CLINICAL OUTCOME OF FUNGAL INFECTIONS OF THE CENTRAL NERVOUS SYSTEM IN ALLOGENEIC STEM CELL TRANSPLANTATION RECIPIENTS

Author

Chiara Cattaneo, Gianpaolo Nadali, Alessandro Busca, Debora Capelli, Livio Pagano, Carlo Castagnola, Anna Candoni, Davide Lazzarotto, L. Melillo, M.I. Del Principe, Luisa Verga, Elisabetta Calore, Katia Perruccio, Gabriele Facchin, and Nikolai Klimko

Subjects
Transplantation, medicine.medical_specialty, medicine.anatomical_structure, business.industry, Immunology, Epidemiology, Central nervous system, Medicine, Hematology, Stem cell, business, Outcome (game theory)
Published
2019

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