Jeffrey D Jenks1,2, Danila Seidel3, Oliver A Cornely3, Sharon Chen4, Sebastiaan van Hal5, Carol Kauffman6, Marisa H Miceli6, Melina Heinemann7, Martin Christner8, Alfredo Jover Sáenz9, Alexander Burchardt10, Björn Kemmerling10, Raoul Herbrecht11, Joerg Steinmann12,13, Shmuel Shoham14, Sandra Gräber15, Livio Pagano16, Dries Deeren17, Monica A Slavin18, Martin Hoenigl1,2,19. 1. Department of Medicine, University of California San Diego, San Diego, United States of America. 2. Clinical and Translational Fungal Research Group, University of California San Diego, San Diego, United States of America. 3. Department I of Internal Medicine, ECMM Excellence Centre of Medical Mycology, CECAD - Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University Hospital Cologne, Cologne, Germany. 4. Centre for Infectious Diseases and Microbiology, Westmead Hospital, and Sydney Medical School, The University of Sydney, Camperdown, New South Wales, Australia. 5. Department of Microbiology and Infectious Diseases, Royal Prince Alfred Hospital, Sydney, Australia, Camperdown. 6. Department of Medicine, University of Michigan, Ann Arbor, United States of America. 7. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 8. Department of Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 9. Territorial Unit of Nosocomial Infection and antibiotic policy (TUNI), University Hospital Arnau de Vilanova, Lleida, Spain. 10. Department of Hematology, Hospital of Justus Liebig University, Giessen, Germany. 11. Department of Oncology and Hematology, Strasbourg University Hospital, Strasbourg, France. 12. Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Klinikum Nürnberg, Paracelsus Medical University, Nuremberg, Germany. 13. Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. 14. Johns Hopkins University School of Medicine, Baltimore, United States of America. 15. Institute of Medical Microbiology and Epidemiology of Infectious Diseases, University Hospital Leipzig, Leipzig, Germany. 16. Department of Hematology, a) Fondazione Policlinico A. Gemelli - IRCCS b) Università Cattolica del Sacro Cuore, Rome, Italy. 17. Department of Hematology, AZ Delta, Roeselare, Belgium. 18. Department of Infectious Diseases, and National Centre for Infections in Cancer, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. 19. Department of Medicine, ECMM Excellence Centre of Medical Mycology, Medical University of Graz, Graz, Austria.
Abstract
OBJECTIVES: Invasive fungal infections caused by Lomentospora prolificans are associated with very high mortality rates and can be challenging to treat given pan-drug resistance to available antifungal agents. The objective of this study was to describe the clinical presentation and outcomes in a cohort of patients with invasive L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection in the FungiScope® registry of rare invasive fungal infections. Patients diagnosed between 01/01/2008 - 09/09/2019 were included in for analysis. RESULTS: The analysis included 41 patients with invasive L. prolificans infection from eight different countries. Haematological/oncological malignancies were the most frequent underlying disease (66%), disseminated infection was frequent (61%), and the lung was the most commonly involved organ (44%). Most infections (59%) were breakthrough infections. Progression/deterioration/treatment failure was observed in 23/40 (58%) of patients receiving antifungal therapy. In total, 21/41 (51%) patients, and 77% of patients with underlying haematological/oncological malignancy, had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was frequent (24/40) and associated with improved survival. In particular, treatment regimens including terbinafine were significantly associated with higher treatment success at final assessment (p=0.012), with a positive trend observed for treatment regimens that included voriconazole (p=0.054). CONCLUSIONS: L. prolificans infections were associated with mortality rates of 77% and above in patients with underlying haematological/oncological malignancies and those with disseminated infections. While combination therapy is the preferred option for now, the hope lies with novel antifungals currently under development. This article is protected by copyright. All rights reserved.
OBJECTIVES:Invasive fungal infections caused by Lomentospora prolificans are associated with very high mortality rates and can be challenging to treat given pan-drug resistance to available antifungal agents. The objective of this study was to describe the clinical presentation and outcomes in a cohort of patients with invasive L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificansinfection in the FungiScope® registry of rare invasive fungal infections. Patients diagnosed between 01/01/2008 - 09/09/2019 were included in for analysis. RESULTS: The analysis included 41 patients with invasive L. prolificansinfection from eight different countries. Haematological/oncological malignancies were the most frequent underlying disease (66%), disseminated infection was frequent (61%), and the lung was the most commonly involved organ (44%). Most infections (59%) were breakthrough infections. Progression/deterioration/treatment failure was observed in 23/40 (58%) of patients receiving antifungal therapy. In total, 21/41 (51%) patients, and 77% of patients with underlying haematological/oncological malignancy, had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was frequent (24/40) and associated with improved survival. In particular, treatment regimens including terbinafine were significantly associated with higher treatment success at final assessment (p=0.012), with a positive trend observed for treatment regimens that included voriconazole (p=0.054). CONCLUSIONS:L. prolificans infections were associated with mortality rates of 77% and above in patients with underlying haematological/oncological malignancies and those with disseminated infections. While combination therapy is the preferred option for now, the hope lies with novel antifungals currently under development. This article is protected by copyright. All rights reserved.
Authors: Martin Hoenigl; Rosanne Sprute; Matthias Egger; Amir Arastehfar; Oliver A Cornely; Robert Krause; Cornelia Lass-Flörl; Juergen Prattes; Andrej Spec; George R Thompson; Nathan Wiederhold; Jeffrey D Jenks Journal: Drugs Date: 2021-10-09 Impact factor: 9.546
Authors: Jeffrey D Jenks; Jean-Pierre Gangneux; Ilan S Schwartz; Ana Alastruey-Izquierdo; Katrien Lagrou; George R Thompson Iii; Cornelia Lass-Flörl; Martin Hoenigl Journal: J Fungi (Basel) Date: 2020-10-11