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Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis |
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J Hepatol. 2021 Apr 9;S0168-8278(21)00230-0. doi: 10.1016/j.jhep.2021.03.026.Online ahead of print.
Javier Martínez 1, Virginia Hernández-Gea 2, Enrique Rodríguez-de-Santiago 1, Luis Téllez 1, Bogdan Procopet 3, Álvaro Giráldez 4, Lucio Amitrano 5, Candid Villanueva 6, Dominique Thabut 7, Luis Ibañez-Samaniego 8, Gilberto Silva-Junior 9, Joan Genescà 10, Christophe Bureau 11, Jonel Trebicka 12, Rafael Bañares 13, Aleksander Krag 14, Elba Llop 15, Wim Laleman 16, Jose María Palazon 17, Jose Castellote 18, Susana Rodrigues 19, Lise L Gluud 20, Carlos Noronha-Ferreira 21, Nuria Cañete 22, Manuel Rodríguez 23, Arnulf Ferlitsch 24, Remy Schwarzer 24, Jose Luis Mundi 25, Henning Gronbaek 26, Manuel Hernández-Guerra 27, Romano Sassatelli 28, Alessandra Dell Era 29, Marco Senzolo 30, Juan G Abraldes 31, Manuel Romero-Gomez 32, Alexander Zipprich 33, Meritxell Casas 34, Helena Masnou 35, Massimo Primignani 36, Frederik Nevens 16, Jose Luis Calleja 15, Christian Jansen 37, Marie Angèle Robic 11, Irene Conejo 10, Maria Vega Catalina 13, Marika Rudler 7, Edilmar Alvarado 6, Valeria Perez-Campuzano 9, Maria Anna Guardascione 5, Petra Fischer 3, Jaime Bosch 38, Juan Carlos García-Pagán 2, Agustín Albillos 39, International Variceal Bleeding Observational Study Group and Baveno Cooperation
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Author information
- 1Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain.
- 2Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain.
- 3Regional Institute of Gastroenterology and Hepatology "Octavian Fodor", Hepatology Department and "Iuliu Hatieganu" University of Medicine and Pharmacy, 3rd Medical Clinic, Cluj-Napoca, Romania.
- 4Unit for the Clinical Management of Digestive Diseases, Virgen del Rocío University Hospital, Instituto de Biomedicina de Sevilla (IBIS), Liver Diseases, Seville, Spain.
- 5Gastroenterology Unit, Ospedale A Cardarelli, Naples, Italy.
- 6Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Department of Gastroenterology and Institut de Recerca, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Universitat Autònoma de Barcelona, Bellaterra (Cerdanyola del Vallès), Barcelona, Spain.
- 7Groupement Hospitalier Pitié-Salpêtrière-Charles Foix, Paris, France; Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine (CRSA), Institute of Cardiometabolism and Nutrition (ICAN), Paris, France.
- 8Servicio de Medicina de Aparato Digestivo Gregorio Marañón, Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid, Spain.
- 9Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain.
- 10Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Liver Unit, Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Research (VHIR), Universitat Autònoma de Barcelona and CIBERehd, Barcelona, Spain.
- 11Department of Hepato-Gastroenterology, Purpan Hospital, CHU Toulouse, INSERM U858, University of Toulouse, Toulouse, France.
- 12Department of Internal Medicine I, Goethe University Frankfurt, Frankfurt, Germany; European Foundation for the Study of Chronic Liver Failure (EF-Clif), Barcelona, Spain.
- 13Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Servicio de Medicina de Aparato Digestivo Gregorio Marañón, Hospital General Universitario Gregorio Marañón, CIBERehd, Madrid, Spain.
- 14Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.
- 15Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Liver Unit, Hospital Universitario Puerta de Hierro. Universidad Autónoma de Madrid, CIBERehd, Madrid, Spain.
- 16Department Gastroenterology and Hepatology. Division of Liver and Biliopancreatic Disorders, University Hospitals Leuven - KU Leuven, Leuven, Belgium.
- 17Hospital General Universitario de Alicante, Alicante, Spain.
- 18Gastroenterology Department, Hepatology Unit, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain.
- 19Gastroenterology and Hepatology Department, Centro Hospitalar São João, Porto, Portugal.
- 20Gastro unit, Medical Division, University Hospital of Hvidovre, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 21Serviço de Gastroenterología e Hepatologia, Hospital de Santa Maria - Centro Hospitalar Universitário Lisboa Norte, Lisbon, Portugal.
- 22Liver Section, Gastroenterology Department, Hospital del Mar, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 23Department of Gastroenterology, Hospital Central de Asturias, Oviedo, Spain.
- 24Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
- 25Department of Gastroenterology, University Hospital San Cecilio, Granada, Spain.
- 26Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark.
- 27Gastroenterology Department, University Hospital of the Canary Islands, La Laguna, Tenerife, Spain.
- 28Unit of Gastroenterology and Digestive Endoscopy, Arcispedale Santa Maria Nuova IRCCS,Reggio Emilia, Italy.
- 29Gastroenterology Unit, ASST Fatebenefratelli Sacco, Department of Clinical and Biomedical Sciences 'Luigi Sacco', University of Milan, Milan, Italy.
- 30Multivisceral Transplant Unit, Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padua, Padua, Italy.
- 31Division of Gastroenterology (Liver Unit), University of Alberta, Edmonton, Canada.
- 32Unidad de Hepatología, Hospital Universitario de Valme, CIBERehd, Sevilla, Spain.
- 33First Department of Internal Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
- 34Hepatology Unit, Digestive Disease Department Hospital de Sabadell, Universitat Autónoma de Barcelona, Sabadell, Spain.
- 35Hospital Universitari Germans Trias i Pujol, Universitat Autònoma Barcelona, Badalona, Spain.
- 36Division of Gastroenterology and Hepatology, IRCCSCa'Granda Maggiore Hospital Foundation, University of Milan, Milan, Italy.
- 37Department of Internal Medicine I, Universitiy of Bonn, Bonn, Germany.
- 38Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; Barcelona Hepatic Hemodynamic Laboratory, Liver Unit, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain; Health Care Provider of the European Reference Network on Rare Liver Disorders (ERN-Liver), Barcelona, Spain; Department of Biomedical research, Bern University, Hepatology, Inselspital, Bern, Switzerland.
- 39Servicio de Gastroenterología y Hepatología, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Universidad de Alcalá, Madrid, Spain; Centro de Investigación Biomédica Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. Electronic address: agustin.albillos@uah.es.
Abstract
Background and aims: Antibiotic prophylaxis reduces the risk of infection and mortality in cirrhotic patients with acute variceal bleeding (AVB). This study examines the incidence and risk factors of bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis.
Methods: Post-hoc analysis of the database of an international, multicenter, observational study designed to examine the role of preemptive TIPS in patients with cirrhosis and AVB. Data collected on patients with cirrhosis hospitalized for AVB (n=2138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization.
Results: 1656 patients out of 1770 (93.6%) received antibiotic prophylaxis, the most frequently used being third-generation cephalosporins (76.2%) and quinolones (19.0%). Of these, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (OR 3.1; 95%CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95%CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95%CI 1.8-3.8), nasogastric tube (OR 1.7; 95%CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95%CI 1.2-4.9).
Conclusion: Bacterial infections develop in almost one fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
Lay summary: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infection is the most frequent and occurs early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.
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