Alexander F A D Schauwvlieghe1, Bart J A Rijnders2, Nele Philips3, Rosanne Verwijs1, Lore Vanderbeke4, Carla Van Tienen5, Katrien Lagrou6, Paul E Verweij7, Frank L Van de Veerdonk8, Diederik Gommers9, Peter Spronk10, Dennis C J J Bergmans11, Astrid Hoedemaekers12, Eleni-Rosalina Andrinopoulou13, Charlotte H S B van den Berg14, Nicole P Juffermans15, Casper J Hodiamont16, Alieke G Vonk17, Pieter Depuydt18, Jerina Boelens19, Joost Wauters3. 1. Department of Internal Medicine, Section of Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands. 2. Department of Internal Medicine, Section of Infectious Diseases, Erasmus MC University Medical Center, Rotterdam, Netherlands. Electronic address: b.rijnders@erasmusmc.nl. 3. Medical Intensive Care Unit, University Hospitals of Leuven, Leuven, Belgium. 4. Medical Intensive Care Unit, University Hospitals of Leuven, Leuven, Belgium; Department of Microbiology and Immunology, KU Leuven University of Leuven, Leuven, Belgium. 5. Department of Viroscience, Erasmus MC University Medical Center, Rotterdam, Netherlands. 6. Department of Laboratory Medicine and National Reference Centre for Mycosis, University Hospitals of Leuven, Leuven, Belgium; Department of Microbiology and Immunology, KU Leuven University of Leuven, Leuven, Belgium. 7. Department of Medical Microbiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; Centre of Expertise in Mycology, Radboudumc/CWZ, Nijmegen, Netherlands. 8. Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. 9. Department of Adult Intensive Care, Erasmus MC University Medical Center, Rotterdam, Netherlands. 10. Department of Intensive Care Medicine, Gelre Hospitals, Apeldoorn, Netherlands. 11. Department of Intensive Care, Maastricht University Medical Centre, Maastricht, Netherlands. 12. Department of Intensive Care, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands. 13. Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, Netherlands. 14. Department of Intensive Care, Academic Medical Centre, Amsterdam, Netherlands; Department of Intensive Care, University Medical Center Groningen, Groningen, Netherlands. 15. Department of Intensive Care, Academic Medical Centre, Amsterdam, Netherlands. 16. Department of Medical Microbiology, Academic Medical Centre, Amsterdam, Netherlands. 17. Department of Medical Microbiology, Erasmus MC University Medical Center, Rotterdam, Netherlands. 18. Department of Intensive Care Medicine, Ghent University, Ghent, Belgium. 19. Department of Laboratory Medicine, and Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium.
Abstract
BACKGROUND: Invasive pulmonary aspergillosis typically occurs in an immunocompromised host. For almost a century, influenza has been known to set up for bacterial superinfections, but recently patients with severe influenza were also reported to develop invasive pulmonary aspergillosis. We aimed to measure the incidence of invasive pulmonary aspergillosis over several seasons in patients with influenza pneumonia in the intensive care unit (ICU) and to assess whether influenza was an independent risk factor for invasive pulmonary aspergillosis. METHODS: We did a retrospective multicentre cohort study. Data were collected from adult patients with severe influenza admitted to seven ICUs across Belgium and The Netherlands during seven influenza seasons. Patients were older than 18 years, were admitted to the ICU for more than 24 h with acute respiratory failure, had pulmonary infiltrates on imaging, and a confirmed influenza infection based on a positive airway PCR test (influenza cohort). We used logistic regression analyses to determine if influenza was independently associated with invasive pulmonary aspergillosis in non-immunocompromised (ie, no European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG] host factor) influenza-positive patients (influenza case group) compared with non-immunocompromised patients with severe community-acquired pneumonia who had a negative airway influenza PCR test (control group). FINDINGS: Data were collected from patients admitted to the ICU between Jan 1, 2009, and June 30, 2016. Invasive pulmonary aspergillosis was diagnosed in 83 (19%) of 432 patients admitted with influenza (influenza cohort), a median of 3 days after admission to the ICU. The incidence was similar for influenza A and B. For patients with influenza who were immunocompromised, incidence of invasive pulmonary aspergillosis was as high as 32% (38 of 117 patients), whereas in the non-immunocompromised influenza case group, incidence was 14% (45 of 315 patients). Conversely, only 16 (5%) of 315 patients in the control group developed invasive pulmonary aspergillosis. The 90-day mortality was 51% in patients in the influenza cohort with invasive pulmonary aspergillosis and 28% in the influenza cohort without invasive pulmonary aspergillosis (p=0·0001). In this study, influenza was found to be independently associated with invasive pulmonary aspergillosis (adjusted odds ratio 5·19; 95% CI 2·63-10·26; p<0·0001), along with a higher APACHE II score, male sex, and use of corticosteroids. INTERPRETATION: Influenza was identified as an independent risk factor for invasive pulmonary aspergillosis and is associated with high mortality. Future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis. FUNDING: None.
BACKGROUND:Invasive pulmonary aspergillosis typically occurs in an immunocompromised host. For almost a century, influenza has been known to set up for bacterial superinfections, but recently patients with severe influenza were also reported to develop invasive pulmonary aspergillosis. We aimed to measure the incidence of invasive pulmonary aspergillosis over several seasons in patients with influenza pneumonia in the intensive care unit (ICU) and to assess whether influenza was an independent risk factor for invasive pulmonary aspergillosis. METHODS: We did a retrospective multicentre cohort study. Data were collected from adult patients with severe influenza admitted to seven ICUs across Belgium and The Netherlands during seven influenza seasons. Patients were older than 18 years, were admitted to the ICU for more than 24 h with acute respiratory failure, had pulmonary infiltrates on imaging, and a confirmed influenza infection based on a positive airway PCR test (influenza cohort). We used logistic regression analyses to determine if influenza was independently associated with invasive pulmonary aspergillosis in non-immunocompromised (ie, no European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG] host factor) influenza-positive patients (influenza case group) compared with non-immunocompromised patients with severe community-acquired pneumonia who had a negative airway influenza PCR test (control group). FINDINGS: Data were collected from patients admitted to the ICU between Jan 1, 2009, and June 30, 2016. Invasive pulmonary aspergillosis was diagnosed in 83 (19%) of 432 patients admitted with influenza (influenza cohort), a median of 3 days after admission to the ICU. The incidence was similar for influenza A and B. For patients with influenza who were immunocompromised, incidence of invasive pulmonary aspergillosis was as high as 32% (38 of 117 patients), whereas in the non-immunocompromised influenza case group, incidence was 14% (45 of 315 patients). Conversely, only 16 (5%) of 315 patients in the control group developed invasive pulmonary aspergillosis. The 90-day mortality was 51% in patients in the influenza cohort with invasive pulmonary aspergillosis and 28% in the influenza cohort without invasive pulmonary aspergillosis (p=0·0001). In this study, influenza was found to be independently associated with invasive pulmonary aspergillosis (adjusted odds ratio 5·19; 95% CI 2·63-10·26; p<0·0001), along with a higher APACHE II score, male sex, and use of corticosteroids. INTERPRETATION: Influenza was identified as an independent risk factor for invasive pulmonary aspergillosis and is associated with high mortality. Future studies should assess whether a faster diagnosis or antifungal prophylaxis could improve the outcome of influenza-associated aspergillosis. FUNDING: None.
Authors: Joshua M Tobin; Kara L Nickolich; Krishnaveni Ramanan; Matthew J Pilewski; Kristina D Lamens; John F Alcorn; Keven M Robinson Journal: J Immunol Date: 2020-06-10 Impact factor: 5.422
Authors: Laura Loughlin; Thomas P Hellyer; P Lewis White; Danny F McAuley; Andrew Conway Morris; Raquel B Posso; Malcolm D Richardson; David W Denning; A John Simpson; Ronan McMullan Journal: Am J Respir Crit Care Med Date: 2020-10-15 Impact factor: 21.405
Authors: Jeffrey D Jenks; Sanjay R Mehta; Randy Taplitz; Saima Aslam; Sharon L Reed; Martin Hoenigl Journal: Mycoses Date: 2019-01-15 Impact factor: 4.377
Authors: Gennaro De Pascale; G Bello; A M Dell'Anna; L Montini; M Antonelli; Gerard Moreno; Alejandro Rodriguez; Ignacio Martin-Loeches Journal: Intensive Care Med Date: 2018-10-24 Impact factor: 17.440
Authors: Marie von Lilienfeld-Toal; Johannes Wagener; Hermann Einsele; Oliver A Cornely; Oliver Kurzai Journal: Dtsch Arztebl Int Date: 2019-04-19 Impact factor: 5.594
Authors: A Arastehfar; A Carvalho; J Houbraken; L Lombardi; R Garcia-Rubio; J D Jenks; O Rivero-Menendez; R Aljohani; I D Jacobsen; J Berman; N Osherov; M T Hedayati; M Ilkit; D James-Armstrong; T Gabaldón; J Meletiadis; M Kostrzewa; W Pan; C Lass-Flörl; D S Perlin; M Hoenigl Journal: Stud Mycol Date: 2021-05-10 Impact factor: 16.097