Javier Fernández1, Verónica Prado2, Jonel Trebicka3, Alex Amoros4, Thierry Gustot5, Reiner Wiest6, Carme Deulofeu4, Elisabet Garcia4, Juan Acevedo7, Valentin Fuhrmann8, François Durand9, Cristina Sánchez4, Maria Papp10, Paolo Caraceni11, Victor Vargas12, Rafael Bañares13, Salvatore Piano14, Martin Janicko15, Agustin Albillos16, Carlo Alessandria17, German Soriano18, Tania M Welzel19, Wim Laleman20, Alexander Gerbes21, Andrea De Gottardi6, Manuela Merli22, Minneke Coenraad23, Faouzi Saliba24, Marco Pavesi4, Rajiv Jalan25, Pere Ginès26, Paolo Angeli14, Vicente Arroyo4. 1. Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain. Electronic address: Jfdez@clinic.ub.es. 2. Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain. 3. European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain; University of Bonn, Germany. 4. European Foundation of Chronic Liver Failure (EF-Clif), Barcelona, Spain. 5. Liver Transplant Unit, Erasme Hospital, Brussels, Belgium. 6. Department of Medicine and Surgery, Inselspital, University of Bern, Bern, Switzerland. 7. South West Liver Unit, Derriford Hospital, UK. 8. University Medical Center Hamburg-Eppendorf, Germany. 9. Hopital Beaujon, Paris, France. 10. Department of Internal Medicine, Division of Gastroenterology, Faculty of Medicine, University of Debrecen, Hungary. 11. University of Bologna, Italy. 12. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain; Hospital Vall d'Hebron, Barcelona, Spain. 13. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain; Hospital Gregorio Marañon, Madrid, Spain. 14. University of Padova, Padova, Italy. 15. Pavol Jozef Safarik University in Kosice, Slovakia. 16. Hospital Universitario Ramon y Cajal, Madrid, Spain. 17. San Giovanni Battista Hospital, Turin, Italy. 18. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain; Hospital of Santa Creu i Sant Pau, Barcelona, Spain. 19. University Hospital of Frankfurt, Germany. 20. University UZ Leuven, Belgium. 21. Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Germany. 22. Sapienza University of Rome, Italy. 23. Leiden University Medical Centre, Netherlands. 24. Centre Hepato-Biliare, Hòpital Paul Brousse, Paris, France. 25. ILDH, Division of Medicine, University College London Medical School, London, United Kingdom. 26. Liver ICU, Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED), ISCIII, Spain.
Abstract
BACKGROUND & AIMS: Antibiotic resistance has been increasingly reported in patients with decompensated cirrhosis in single-center studies. Prospective investigations reporting broad epidemiological data are scarce. We aimed to analyze epidemiological changes in bacterial infections in patients with decompensated cirrhosis. METHODS: This was a prospective evaluation of 2 series of patients hospitalized with decompensated cirrhosis. The Canonic series included 1,146 patients from Northern, Southern and Western Europe in 2011. Data on epidemiology, clinical characteristics of bacterial infections, microbiology and empirical antibiotic schedules were assessed. A second series of 883 patients from Eastern, Southern and Western Europe was investigated between 2017-2018. RESULTS: A total of 455 patients developed 520 infections (39.7%) in the first series, with spontaneous bacterial peritonitis, urinary tract infections and pneumonia the most frequent infections. Nosocomial episodes predominated in this series. Nearly half of the infections were culture-positive, of which 29.2% were caused by multidrug-resistant organisms (MDROs). MDR strains were more frequently isolated in Northern and Western Europe. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were the most frequent MDROs isolated in this series, although prevalence and type differed markedly among countries and centers. Antibiotic resistance was associated with poor prognosis and failure of antibiotic strategies, based on third-generation cephalosporins or quinolones. Nosocomial infection (odds ratio [OR] 2.74; p < 0.001), intensive care unit admission (OR 2.09; p = 0.02), and recent hospitalization (OR 1.93; p = 0.04) were identified as independent predictors of MDR infection. The prevalence of MDROs in the second series (392 infections/284 patients) was 23%; 38% in culture-positive infections. A mild increase in the rate of carbapenem-resistant Enterobacteriaceae was observed in this series. CONCLUSIONS: MDR bacterial infections constitute a prevalent, growing and complex healthcare problem in patients with decompensated cirrhosis and acute-on-chronic liver failure across Europe, negatively impacting on prognosis. Strategies aimed at preventing the spread of antibiotic resistance in cirrhosis should be urgently evaluated. LAY SUMMARY: Infections caused by bacteria resistant to the main antibiotic families are prevalent in patients with cirrhosis. This study demonstrates that this healthcare problem is increasing and extends through all European regions. Infections caused by these difficult to treat bacteria resolve less frequently and often cause the death of the patient. The type of resistant bacteria varies markedly among different hospitals.
BACKGROUND & AIMS: Antibiotic resistance has been increasingly reported in patients with decompensated cirrhosis in single-center studies. Prospective investigations reporting broad epidemiological data are scarce. We aimed to analyze epidemiological changes in bacterial infections in patients with decompensated cirrhosis. METHODS: This was a prospective evaluation of 2 series of patients hospitalized with decompensated cirrhosis. The Canonic series included 1,146 patients from Northern, Southern and Western Europe in 2011. Data on epidemiology, clinical characteristics of bacterial infections, microbiology and empirical antibiotic schedules were assessed. A second series of 883 patients from Eastern, Southern and Western Europe was investigated between 2017-2018. RESULTS: A total of 455 patients developed 520 infections (39.7%) in the first series, with spontaneous bacterial peritonitis, urinary tract infections and pneumonia the most frequent infections. Nosocomial episodes predominated in this series. Nearly half of the infections were culture-positive, of which 29.2% were caused by multidrug-resistant organisms (MDROs). MDR strains were more frequently isolated in Northern and Western Europe. Extended-spectrum beta-lactamase-producing Enterobacteriaceae were the most frequent MDROs isolated in this series, although prevalence and type differed markedly among countries and centers. Antibiotic resistance was associated with poor prognosis and failure of antibiotic strategies, based on third-generation cephalosporins or quinolones. Nosocomial infection (odds ratio [OR] 2.74; p < 0.001), intensive care unit admission (OR 2.09; p = 0.02), and recent hospitalization (OR 1.93; p = 0.04) were identified as independent predictors of MDR infection. The prevalence of MDROs in the second series (392 infections/284 patients) was 23%; 38% in culture-positive infections. A mild increase in the rate of carbapenem-resistant Enterobacteriaceae was observed in this series. CONCLUSIONS: MDR bacterial infections constitute a prevalent, growing and complex healthcare problem in patients with decompensated cirrhosis and acute-on-chronic liver failure across Europe, negatively impacting on prognosis. Strategies aimed at preventing the spread of antibiotic resistance in cirrhosis should be urgently evaluated. LAY SUMMARY: Infections caused by bacteria resistant to the main antibiotic families are prevalent in patients with cirrhosis. This study demonstrates that this healthcare problem is increasing and extends through all European regions. Infections caused by these difficult to treat bacteria resolve less frequently and often cause the death of the patient. The type of resistant bacteria varies markedly among different hospitals.