Influenza and associated co-infections in critically ill immunosuppressed patients
Ignacio Martin-Loeches,
Virginie Lemiale,
Pierce Geoghegan,
Mary Aisling McMahon,
Peter Pickkers,
Marcio Soares,
Anders Perner,
Tine Sylvest Meyhoff,
Ramin Brandt Bukan,
Jordi Rello,
Philippe R. Bauer,
Andry van de Louw,
Fabio Silvio Taccone,
Jorge Salluh,
Pleun Hemelaar,
Peter Schellongowski,
Katerina Rusinova,
Nicolas Terzi,
Sangeeta Mehta,
Massimo Antonelli,
Achille Kouatchet,
Pål Klepstad,
Miia Valkonen,
Precious Pearl Landburg,
Andreas Barratt-Due,
Fabrice Bruneel,
Frédéric Pène,
Victoria Metaxa,
Anne Sophie Moreau,
Virginie Souppart,
Gaston Burghi,
Christophe Girault,
Ulysses V. A. Silva,
Luca Montini,
Francois Barbier,
Lene B. Nielsen,
Benjamin Gaborit,
Djamel Mokart,
Sylvie Chevret,
Elie Azoulay,
For the Efraim investigators and the Nine-I study group
Affiliations
Ignacio Martin-Loeches
Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James’s Hospital
Virginie Lemiale
Medical Intensive Care Unit, Hôpital Saint-Louis and Paris Diderot Sorbonne University
Pierce Geoghegan
Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James’s Hospital
Mary Aisling McMahon
Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St. James’s Hospital
Peter Pickkers
Department of Intensive Care Medicine (710), Radboud University Medical Centre
Marcio Soares
Department of Critical Care and Graduate Program in Translational Medicine, Programa de Pós-Graduação em Clínica Médica, D’Or Institute for Research and Education
Anders Perner
Department of Intensive Care, Rigshospitalet, University of Copenhagen
Tine Sylvest Meyhoff
Department of Intensive Care, Rigshospitalet, University of Copenhagen
Ramin Brandt Bukan
Department of Anesthesiology I, Herlev University Hospital
Jordi Rello
CIBERES, Universitat Autonòma de Barcelona, European Study Group of Infections in Critically Ill Patients (ESGCIP)
Philippe R. Bauer
Pulmonary and Critical Care Medicine, Mayo Clinic
Andry van de Louw
Division of Pulmonary and Critical Care, Penn State University College of Medicine
Fabio Silvio Taccone
Department of Intensive Care, Hôpital Erasme, Université Libre de Bruxelles (ULB)
Jorge Salluh
Department of Critical Care and Graduate Program in Translational Medicine, Programa de Pós-Graduação em Clínica Médica, D’Or Institute for Research and Education
Pleun Hemelaar
Department of Intensive Care Medicine (710), Radboud University Medical Centre
Peter Schellongowski
Department of Medicine I, Medical University of Vienna
Katerina Rusinova
Department of Anesthesiology and Intensive Care Medicine and Institute for Medical Humanities, 1st Faculty of Medicine, Charles University in Prague and General University Hospital
Nicolas Terzi
CHU Grenoble Alpes, Service de Réanimation Médicale, Faculté de Médecine de Grenoble, INSERM U1042, Université Grenoble-Alpes
Sangeeta Mehta
Department of Medicine and Interdepartmental Division of Critical Care Medicine, Sinai Health System, University of Toronto
Massimo Antonelli
Agostino Gemelli University Hospital, Università Cattolica del Sacro Cuore
Achille Kouatchet
Department of Medical Intensive Care Medicine, University Hospital of Angers
Pål Klepstad
Norwegian University of Science and Technology
Miia Valkonen
Division of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, Helsinki University Hospital, University of Helsinki
Precious Pearl Landburg
Department of Critical Care, University Medical Center Groningen
Andreas Barratt-Due
Department of Immunology–Department of Emergencies and Critical Care, University of Oslo
Fabrice Bruneel
Medical-Surgical Intensive Care Unit, Centre Hospitalier de Versailles
Frédéric Pène
Medical ICU, Cochin Hospital, Assistance Publique-Hôpitaux de Paris and University Paris Descartes
Victoria Metaxa
Critical Care Department, King’s College Hospital NHS Foundation Trust
Anne Sophie Moreau
Critical Care Center, CHU Lille, School of Medicine, University of Lille
Virginie Souppart
Medical Intensive Care Unit, Hôpital Saint-Louis and Paris Diderot Sorbonne University
Gaston Burghi
Terapia Intensiva, Hospital Maciel
Christophe Girault
Department of Medical Intensive Care, Normandie Univ, UNIROUEN, EA-3830, Rouen University Hospital
Ulysses V. A. Silva
ICU, Fundação Pio XII - Barretos Cancer Hospital
Luca Montini
Agostino Gemelli University Hospital, Università Cattolica del Sacro Cuore
Francois Barbier
Medical Intensive Care Unit, La Source Hospital - CHR Orléans
Lene B. Nielsen
Intensive Care Department, University of Southern Denmark
Benjamin Gaborit
Medical Intensive Care Unit, Hôtel Dieu-HME-University Hospital of Nantes
Djamel Mokart
Réanimation Polyvalente et Département d’Anesthésie et de Réanimation, Institut Paoli-Calmettes
Sylvie Chevret
ECSTRA Team, Biostatistics and Clinical Epidemiology, UMR 1153, INSERM, Paris Diderot Sorbonne University and Service de Biostatistique et Information Médicale AP-HP, Hôpital Saint-Louis
Elie Azoulay
Medical Intensive Care Unit, Hôpital Saint-Louis and Paris Diderot Sorbonne University
For the Efraim investigators and the Nine-I study group
Abstract Background It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. Methods Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. Results Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90–1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. Conclusions Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.