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.

Agostino Gemelli University Hospital Università Cattolica del Sacro Cuore Rome Italy

CHU Grenoble Alpes Service de Réanimation Médicale Faculté de Médecine de Grenoble INSERM U1042 Université Grenoble Alpes Grenoble France

CIBERES Universitat Autonòma de Barcelona European Study Group of Infections in Critically Ill Patients Barcelona Spain

Critical Care Center CHU Lille School of Medicine University of Lille Lille France

Critical Care Department King's College Hospital NHS Foundation Trust London SE5 9RS UK

Department of Anaesthesia and Intensive Care Odense University Hospital Odense Denmark

Department of Anesthesiology 1 Herlev University Hospital Herlev Denmark

Department of Anesthesiology and Intensive Care Medicine and Institute for Medical Humanities 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Clinical Medicine Wellcome Trust HRB Clinical Research Facility St James Hospital Trinity College Dublin Ireland

Department of Critical Care and Graduate Program in Translational Medicine Programa de Pós Graduação em Clínica Médica D'Or Institute for Research and Education Rio de Janeiro Brazil

Department of Critical Care University Medical Center Groningen Groningen The Netherlands

Department of Immunology Department of Emergencies and Critical Care University of Oslo Oslo Norway

Department of Intensive Care Hôpital Erasme Université Libre de Bruxelles Brussels Belgium

Department of Intensive Care Medicine Multidisciplinary Intensive Care Research Organization St James's Hospital Dublin Ireland

Department of Intensive Care Medicine Radboud University Medical Centre Nijmegen The Netherlands

Department of Intensive Care Medicine St James's Hospital St James's St Dublin Dublin 8 Ireland

Department of Intensive Care Rigshospitalet University of Copenhagen Copenhagen Denmark

Department of Medical Intensive Care Medicine University Hospital of Angers Angers France

Department of Medical Intensive Care Normandie Univ UNIROUEN EA 3830 Rouen University Hospital F 76000 Rouen France

Department of Medicine 1 Medical University of Vienna Vienna Austria

Department of Medicine and Interdepartmental Division of Critical Care Medicine Sinai Health System University of Toronto Toronto Ontario Canada

Division of Intensive Care Medicine Department of Anesthesiology Intensive Care and Pain Medicine Helsinki University Hospital University of Helsinki Helsinki Finland

Division of Pulmonary and Critical Care Penn State University College of Medicine Hershey PA USA

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 Saint Louis France

ICU Fundação Pio XII Barretos Cancer Hospital Barretos Brazil

Intensive Care Department University of Southern Denmark Sønderborg Denmark

Medical ICU Cochin Hospital Assistance Publique Hôpitaux de Paris and University Paris Descartes Paris France

Medical Intensive Care Unit Hôpital Saint Louis and Paris Diderot Sorbonne University Paris France

Medical Intensive Care Unit Hôtel Dieu HME University Hospital of Nantes Nantes France

Medical Intensive Care Unit La Source Hospital CHR Orléans Orléans France

Medical Surgical Intensive Care Unit Centre Hospitalier de Versailles Le Chesnay France

Norwegian University of Science and Technology Trondheim Norway

Pulmonary and Critical Care Medicine Mayo Clinic Rochester MN USA

Réanimation Polyvalente et Département d'Anesthésie et de Réanimation Institut Paoli Calmettes Marseille France

Terapia Intensiva Hospital Maciel Montevideo Uruguay

Zobrazit více v PubMed

Azoulay E, Afessa B. The intensive care support of patients with malignancy: do everything that can be done. Intensive Care Med. 2006;32:3–5. doi: 10.1007/s00134-005-2835-6. PubMed DOI

Nseir S, Di Pompeo C, Diarra M, Brisson H, Tissier S, Boulo M, Durocher A. Relationship between immunosuppression and intensive care unit-acquired multidrug-resistant bacteria: a case-control study. Crit Care Med. 2007;35:1318–1323. doi: 10.1097/01.CCM.0000261885.50604.20. PubMed DOI

Boomer JS, To K, Chang KC, Takasu O, Osborne DF, Walton AH, Bricker TL, Jarman SD, Kreisel D, Krupnick AS, Srivastava A, Swanson PE, Green JM, Hotchkiss RS. Immunosuppression in patients who die of sepsis and multiple organ failure. JAMA. 2011;306:2594–2605. doi: 10.1001/jama.2011.1829. PubMed DOI PMC

Kash JC, Taubenberger JK. The role of viral, host, and secondary bacterial factors in influenza pathogenesis. Am J Pathol. 2015;185:1528–1536. doi: 10.1016/j.ajpath.2014.08.030. PubMed DOI PMC

Fowlkes A, Steffens A, Temte J, Di Lonardo S, McHugh L, Martin K, Rubino H, Feist M, Davis C, Selzer C, Lojo J, Oni O, Kurkjian K, Thomas A, Boulton R, Bryan N, Lynfield R, Biggerstaff M, Finelli L, Influenza Incidence Surveillance Project Working Group Incidence of medically attended influenza during pandemic and post-pandemic seasons through the influenza incidence surveillance project, 2009-13. Lancet Respir Med. 2015;3:709–718. doi: 10.1016/S2213-2600(15)00278-7. PubMed DOI PMC

Díaz E, Rodríguez A, Martin-Loeches I, Lorente L, del Mar Martín M, Pozo JC, Montejo JC, Estella A, Arenzana A, Rello J. Impact of obesity in patients infected with 2009 influenza A(H1N1) Chest. 2011;139:382–386. doi: 10.1378/chest.10-1160. PubMed DOI

Napolitano LM, Angus DC, Uyeki TM. Critically ill patients with influenza A(H1N1)pdm09 virus infection in 2014. JAMA. 2014;311(13):1289-90. 10.1001/jama.2014.2116. PubMed PMC

Martin-Loeches I, Díaz E, Vidaur L, Torres A, Laborda C, Granada R, Bonastre J, Martín M, Insausti J, Arenzana A, Guerrero JE, Navarrete I, Bermejo-Martin J, Suarez D, Rodriguez A. Pandemic and post-pandemic influenza A (H1N1) infection in critically ill patients. Crit Care. 2011;15:R286. doi: 10.1186/cc10573. PubMed DOI PMC

Martin-Loeches I, Schultz JM, Vincent J-L, Alvarez-Lerma F, Bos LD, Solé-Violán J, Torres A, Rodriguez A, Sole-Violan J, Torres A, Rodriguez A. Increased incidence of co-infection in critically ill patients with influenza. Intensive Care Med. 2017;43(1):48-58. 10.1007/s00134-016-4578-y. Epub 2016 Oct 5. PubMed

Cawcutt K, Kalil AC. Pneumonia with bacterial and viral coinfection. Curr Opin Crit Care. 2017;23:385–390. doi: 10.1097/MCC.0000000000000435. PubMed DOI

White DB, Angus DC. Preparing for the sickest patients with 2009 influenza A(H1N1) JAMA. 2009;302:1905–1906. doi: 10.1001/jama.2009.1539. PubMed DOI

Visseaux B, Burdet C, Voiriot G, Lescure F-X, Chougar T, Brugière O, Crestani B, Casalino E, Charpentier C, Descamps D, Timsit J-F, Yazdanpanah Y, Houhou-Fidouh N. Prevalence of respiratory viruses among adults, by season, age, respiratory tract region and type of medical unit in Paris, France, from 2011 to 2016. PLoS One. 2017;12:e0180888. doi: 10.1371/journal.pone.0180888. PubMed DOI PMC

Azoulay E, Pickkers P, Soares M, Perner A, Rello J, Bauer PR, van de Louw A, Hemelaar P, Lemiale V, Taccone FS, Martin Loeches I, Meyhoff TS, Salluh J, Schellongowski P, Rusinova K, Terzi N, Mehta S, Antonelli M, Kouatchet A, Barratt-Due A, Valkonen M, Landburg PP, Bruneel F, Bukan RB, Pène F, Metaxa V, Moreau AS, Souppart V, Burghi G, Girault C, et al. Acute hypoxemic respiratory failure in immunocompromised patients: the Efraim multinational prospective cohort study. Intensive Care Med. 2017;43(12):1808-19. 10.1007/s00134-017-4947-1. Epub 2017 Sep 25. PubMed

https://www.cdc.gov/flu/pdf/freeresources/healthcare/flu-specimen-collection-guide.pdf Acccesed 14 Mar 12, 2019.

Contejean A, Lemiale V, Resche-Rigon M, Mokart D, Pène F, Kouatchet A, Mayaux J, Vincent F, Nyunga M, Bruneel F, Rabbat A, Perez P, Meert A-P, Benoit D, Hamidfar R, Darmon M, Jourdain M, Renault A, Schlemmer B, Azoulay E. Increased mortality in hematological malignancy patients with acute respiratory failure from undetermined etiology: a Groupe de Recherche en Réanimation Respiratoire en Onco-Hématologie (GRRR-OH) study. Ann Intensive Care. 2016;6:102. doi: 10.1186/s13613-016-0202-0. PubMed DOI PMC

J T, Vincent JL, Moreno R, Takala J, Willatts S, De Mendonça A, Bruining H, Reinhart CK, Suter PM, Thijs LG. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22:707–710. doi: 10.1007/BF01709751. PubMed DOI

Rodríguez AH, Avilés-Jurado FX, Díaz E, Schuetz P, Trefler SI, Solé-Violán J, Cordero L, Vidaur L, Estella Á, Pozo Laderas JC, Socias L, Vergara JC, Zaragoza R, Bonastre J, Guerrero JE, Suberviola B, Cilloniz C, Restrepo MI, Martín-Loeches I, Cobo P, Martins J, Carbayo C, Robles-Musso E, Cárdenas A, Fierro J, Fernández DO, Sierra R, Huertos MJ, Carmona Pérez ML, Pozo Laderas JC, et al. Procalcitonin (PCT) levels for ruling-out bacterial coinfection in ICU patients with influenza: a CHAID decision-tree analysis. J Inf Secur. 2016;72:143–151. PubMed

Martin-Loeches I, Levy MMMM, Artigas A. Management of severe sepsis: advances, challenges, and current status. Drug Des Devel Ther. 2015;9:2079–2088. doi: 10.2147/DDDT.S78757. PubMed DOI PMC

Álvarez-Lerma F, Marín-Corral J, Vilà C, Masclans JR, Loeches IM, Barbadillo S, González de Molina FJ, Rodríguez A, H1N1 GETGAG/SEMICYUC Study Group Characteristics of patients with hospital-acquired influenza A (H1N1)pdm09 virus admitted to the intensive care unit. J Hosp Infect. 2017;95:200–206. doi: 10.1016/j.jhin.2016.12.017. PubMed DOI

Zafrani L, Azoulay E. How to treat severe infections in critically ill neutropenic patients? BMC Infect Dis. 2014;14:512. doi: 10.1186/1471-2334-14-512. PubMed DOI PMC

Vilar-Compte D, Shah DP, Vanichanan J, Cornejo-Juarez P, Garcia-Horton A, Volkow P, Chemaly RF. Influenza in patients with hematological malignancies: experience at two comprehensive cancer centers. J Med Virol. 2018;90:50–60. doi: 10.1002/jmv.24930. PubMed DOI PMC

Martin-Loeches I, Rodriguez A, Sanchez-Corral A, Granada R, Zaragoza R, Albaya A, Cerda E, Catalan R, Luque P, Paredes A, et al.: Bacterial co-infection in critically ill patients infected with pandemic (H1N1) v influenza A infection. In Intensive Care Med. Volume 36; 2010:S369--S369.

Matos RG, Moreno RP, Diogo AC, Pereira JM, Martin-Loeches I, Cecconi M, Lisboa T, Rhodes A, Rello J. Intensive care med. Volume 36. 2010. Bacterial pneumonia complicating influenza A (H1N1) v viral pneumonia: results of the ESICM influenza A (H1N1) v registry; p. S371.

Muscedere J, Ofner M, Kumar A, Long J, Lamontagne F, Cook D, McGeer A, Chant C, Marshall J, Jouvet P, Fowler R, ICU-FLU Group, Canadian Critical Care Trials Group The occurrence and impact of bacterial organisms complicating critical care illness associated with 2009 influenza A(H1N1) infection. Chest. 2013;144:39–47. doi: 10.1378/chest.12-1861. PubMed DOI

Mc Mahon A, Martin-Loeches I. The pharmacological management of severe influenza infection - 'existing and emerging therapies'. Expert Rev Clin Pharmacol. 2017;10(1):81-95. 10.1080/17512433.2017.1255550. Epub 2016 Nov 25. PubMed

Acute respiratory failure in immunocompromised patients: outcome and clinical features according to neutropenia status