Anne Coste1,2, Aurélien Frérou3, Anaïs Raute4, Francis Couturaud5, Jean Morin6, Pierre-Yves Egreteau4, François-Xavier Blanc6, Jean Reignier7, Jean-Marc Tadié3, Adissa Tran8, Charlotte Pronier9, Marianne Coste-Burel10, Gilles Nevez8, Jean-Pierre Gangneux11, Patrice Le Pape12, Séverine Ansart2, Jean-Marie Tonnelier1, Cédric Bretonnière6, Cécile Aubron1. 1. Medical Intensive Care Unit, Centre Hospitalier et Universitaire de Brest, Université de Bretagne Occidentale, Brest, France. 2. Department of Infectious Diseases, Centre Hospitalier et Universitaire de Brest, Université de Bretagne Occidentale, Brest, France. 3. Medical Intensive Care Unit, Centre Hospitalier et Universitaire de Rennes, Rennes, France. 4. Intensive Care Unit, Centre Hospitalier des Pays de Morlaix, Morlaix, France. 5. Department of Pneumology, Centre Hospitalier et Universitaire de Brest, Université de Bretagne Occidentale, EA3878-GETBO, CIC_INSERM1412, Brest, France. 6. Respiratory Intensive Care Unit, Centre Hospitalier et Universitaire de Nantes, Nantes, France. 7. Medical Intensive Care Unit, Centre Hospitalier et Universitaire de Nantes, Nantes, France. 8. Department of Parasitology and Mycology, ER GEIHP, Université d'Angers, Université de Brest, Centre Hospitalier et Universitaire de Brest, Brest, France. 9. Department of Virology, Centre Hospitalier et Universitaire Rennes, Université de Rennes, Inserm, EHESP, IRSET (Institut de recherche en santeé, environnement et travail) - UMR_S 1085, F-35000 Rennes, France. 10. Department of Virology, Centre Hospitalier et Universitaire de Nantes, Nantes, France. 11. Department of Microbiology, Mycology-Parasitology Laboratory, Centre Hospitalier et Universitaire de Rennes, Université de Rennes, INSERM, EHESP, IRSET (Institut de Recherche en Santé, environnement et travail) - UMR_1085, F-35000 Rennes, France. 12. Department of Parasitology and Mycology, Centre Hospitalier et Universitaire de Nantes, Nantes, France.
Abstract
OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.
OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically illpatients with severe influenzapneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus-positive pulmonary culture. Factors independently associated with Aspergillus-positive culture were liver cirrhosis (odds ratio = 6.7 [2.1-19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2-8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6-9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6-12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus-positive pulmonary culture (p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically illpatients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.