دورية أكاديمية
Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial.
| العنوان: | Posaconazole for prevention of invasive pulmonary aspergillosis in critically ill influenza patients (POSA-FLU): a randomised, open-label, proof-of-concept trial. |
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| المؤلفون: | Vanderbeke L; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium., Janssen NAF; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Center of Expertise in Mycology Radboudumc/CWZ, Radboudumc Center for Infectious Diseases (RCI), Nijmegen, The Netherlands., Bergmans DCJJ; Department of Intensive Care Medicine, Maastricht University Medical Center, Maastricht, The Netherlands., Bourgeois M; Department of Intensive Care, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende, Brugge, Belgium., Buil JB; Center of Expertise in Mycology Radboudumc/CWZ, Radboudumc Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Debaveye Y; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.; Department of Intensive Care Medicine, University Hospitals Leuven, Leuven, Belgium., Depuydt P; Department of Intensive Care Medicine, Ghent University Hospital, Ghent, Belgium., Feys S; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium., Hermans G; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium.; Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium., Hoiting O; Department of Intensive Care Medicine, Canisius Wilhelmina Hospital, Nijmegen, The Netherlands., van der Hoven B; Department of Intensive Care Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands., Jacobs C; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium., Lagrou K; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.; Department of Laboratory Medicine and National Reference Center for Mycosis, University Hospitals Leuven, Leuven, Belgium., Lemiale V; Department of Intensive Care Medicine, Saint-Louis Hospital, Paris, France., Lormans P; Department of Anesthesiology and Intensive Care Medicine, Algemeen Ziekenhuis Delta, Roeselare, Belgium., Maertens J; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.; Department of Haematology, University Hospitals Leuven, Leuven, Belgium., Meersseman P; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium., Mégarbane B; Department of Medical and Toxicological Critical Care, Lariboisière Hospital, INSERM UMRS-1144, University of Paris, Paris, France., Nseir S; Department of Intensive Care Medicine, Critical Care Center, University Hospital Lille, INSERM U995-E2, Lille Inflammation Research International Center, University of Lille, Lille, France., van Oers JAH; Department of Intensive Care Medicine, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands., Reynders M; Department of Laboratory Medicine, Algemeen Ziekenhuis Sint-Jan Brugge-Oostende, Brugge, Belgium., Rijnders BJA; Department of Internal Medicine, Section of Infectious Diseases, Erasmus University Medical Center, Rotterdam, The Netherlands., Schouten JA; Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, The Netherlands., Spriet I; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.; Department of Pharmacy, University Hospitals Leuven, Leuven, Belgium., Thevissen K; Department of Microbial and Molecular Systems, Center of Microbial and Plant Genetics (CMPG), KU Leuven, Leuven, Belgium., Thille AW; Department of Intensive Care Medicine, University Hospital Poitiers, Poitiers, France., Van Daele R; Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.; Department of Pharmacy, University Hospitals Leuven, Leuven, Belgium., van de Veerdonk FL; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.; Center of Expertise in Mycology Radboudumc/CWZ, Radboudumc Center for Infectious Diseases (RCI), Nijmegen, The Netherlands., Verweij PE; Center of Expertise in Mycology Radboudumc/CWZ, Radboudumc Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.; Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, The Netherlands., Wilmer A; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium.; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium., Brüggemann RJM; Center of Expertise in Mycology Radboudumc/CWZ, Radboudumc Center for Infectious Diseases (RCI), Nijmegen, The Netherlands.; Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands., Wauters J; Department of Microbiology, Immunology and Transplantation, KU Leuven, Leuven, Belgium. joost.wauters@uzleuven.be.; Medical Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium. joost.wauters@uzleuven.be. |
| مؤلفون مشاركون: | Dutch-Belgian Mycosis Study Group |
| المصدر: | Intensive care medicine [Intensive Care Med] 2021 Jun; Vol. 47 (6), pp. 674-686. Date of Electronic Publication: 2021 May 29. |
| نوع المنشور: | Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Verlag Country of Publication: United States NLM ID: 7704851 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1238 (Electronic) Linking ISSN: 03424642 NLM ISO Abbreviation: Intensive Care Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York : Springer Verlag Original Publication: Berlin ; New York, Springer International. |
| مواضيع طبية MeSH: | Influenza, Human*/complications , Influenza, Human*/drug therapy , Influenza, Human*/prevention & control , Invasive Pulmonary Aspergillosis*/drug therapy , Invasive Pulmonary Aspergillosis*/prevention & control, Adult ; Critical Illness ; Humans ; Intensive Care Units ; Triazoles |
| مستخلص: | Purpose: Influenza-associated pulmonary aspergillosis (IAPA) is a frequent complication in critically ill influenza patients, associated with significant mortality. We investigated whether antifungal prophylaxis reduces the incidence of IAPA. Methods: We compared 7 days of intravenous posaconazole (POS) prophylaxis with no prophylaxis (standard-of-care only, SOC) in a randomised, open-label, proof-of-concept trial in patients admitted to an intensive care unit (ICU) with respiratory failure due to influenza (ClinicalTrials.gov, NCT03378479). Adult patients with PCR-confirmed influenza were block randomised (1:1) within 10 days of symptoms onset and 48 h of ICU admission. The primary endpoint was the incidence of IAPA during ICU stay in patients who did not have IAPA within 48 h of ICU admission (modified intention-to-treat (MITT) population). Results: Eighty-eight critically ill influenza patients were randomly allocated to POS or SOC. IAPA occurred in 21 cases (24%), the majority of which (71%, 15/21) were diagnosed within 48 h of ICU admission, excluding them from the MITT population. The incidence of IAPA was not significantly reduced in the POS arm (5.4%, 2/37) compared with SOC (11.1%, 4/36; between-group difference 5.7%; 95% CI - 10.8 to 21.7; p = 0.32). ICU mortality of early IAPA was high (53%), despite rapid antifungal treatment. Conclusion: The higher than expected incidence of early IAPA precludes any definite conclusion on POS prophylaxis. High mortality of early IAPA, despite timely antifungal therapy, indicates that alternative management strategies are required. After 48 h, still 11% of patients developed IAPA. As these could benefit from prophylaxis, differentiated strategies are likely needed to manage IAPA in the ICU. |
| التعليقات: | Comment in: Intensive Care Med. 2021 Nov;47(11):1341-1342. (PMID: 34374834) Comment in: Intensive Care Med. 2021 Nov;47(11):1343-1344. (PMID: 34608528) |
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| فهرسة مساهمة: | Investigator: B Rijnders; P Verweij; F van de Veerdonk; A Schauwvlieghe; T Wolfs; J Wauters; K Lagrou Keywords: Aspergillosis; Critical illness; Influenza; Posaconazole; Prophylaxis |
| سلسلة جزيئية: | ClinicalTrials.gov NCT03378479 |
| المشرفين على المادة: | 0 (Triazoles) 6TK1G07BHZ (posaconazole) |
| تواريخ الأحداث: | Date Created: 20210529 Date Completed: 20210708 Latest Revision: 20220218 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC8164057 |
| DOI: | 10.1007/s00134-021-06431-0 |
| PMID: | 34050768 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1432-1238 |
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| DOI: | 10.1007/s00134-021-06431-0 |