Determinants of clinical response to empirical antibiotic treatment in patients with cirrhosis and bacterial and fungal infections- Results from the ICA ‘Global study’ [EABCIR-Global Study]

Author:

Maiwall Rakhi1,Piano Salvatore2,Singh Virendra3,Caraceni Paolo4,Alessandria Carlo5,Fernandez Javier6789,Soares Elza Cotrim10,Kim Dong Joon11,Kim Sung Eun12,Marino Monica13,Vorobioff Julio14,Ribeiro Barea Rita de Cassia15,Merli Manuela16,Elkrief Laure17,Vargas Victor18,Krag Aleksander19,Singh Shivaram Prasad20,Lesmana Laurentius Adrianto21,Toledo Claudio22,Marciano Sebastian23,Verhelst Xavier24,Wong Florence25,Intagliata Nicolas26,Rabinowich Liane27,Colombato Luis28,Kim Sang Gyune29,Gerbes Alexander30,Durand Francois31,Roblero Juan Pablo32,Bhamidimarri Kalyan Ram33,Maevskaya Marina34,Fassio Eduardo35,Kim Hyoung Su36,Hwang Jae Seok37,Gines Pere678,Bruns Tony3839,Gadano Adrian23,Angeli Paolo2,Sarin Shiv Kumar1,

Affiliation:

1. Department of Hepatology, Institute of Liver and Biliary Sciences, New Dehli, India

2. Unit of Internal Medicine and Hepatology (UIMH), Department of Medicine – DIMED, University of Padova, Padova, Italy

3. Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

4. Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

5. Division of Gastroenterology and Hepatology, Città della Salute e della Scienza Hospital, University of Turin, Turin, Italy

6. Liver ICU, Liver Unit, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain

7. Institut d’Investigacions Biomèdiques August-Pi-Sunyer (IDIBAPS)

8. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHED)

9. European Foundation of Chronic Liver Failure (EF-Clif), Barcelona

10. Gastroenterology Division, Medicine Department, Faculty of Medical Sciences, University of Campinas (UNICAMP). Campinas, São Paulo, Brazil

11. Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, South Korea

12. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym Sacred Heart Hospital, College of Medicine, Hallym University, Anyang city, Republic of Korea

13. Liver Unit, Hospital Dr. Carlos B. Udaondo, Buenos Aires, Argentina

14. Rosario University Medical School, Rosario, Argentina

15. Serviço de Hepatologia do HRMS, Hospital Regional de Mato Grosso Do Sul- HRMS, Campo Grande, Brazil

16. Gastroenterology and Hepatology Unit, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy

17. Service de Transplantation, Service d’Hépato-gastroentérologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland

18. Liver Unit, Department of Internal Medicine, Hospital Vall d’Hebron, Universitat Autònoma de Barcelona, CIBERehd, Barcelona. Spain

19. Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark

20. Department of Gastroenterology, S.C.B. Medical College, Cuttack, India

21. Digestive Disease and Oncology Centre, Medistra Hospital, Jakarta, Indonesia

22. Gastroenterology Unit, Hospital Valdivia, Universidad Austral de Chile, Valdivia, Chile

23. Liver Unit and Department of Research, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

24. Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium

25. Division of Gastroenterology, Department of Medicine, University of Toronto, Ontario, Canada

26. Division of Gastroenterology and Hepatology, University of Virginia, Charlottesville, Virginia, USA

27. Liver Unit, Department of Gastroenterology, Tel-Aviv Medical Center and Tel-Aviv University, Tel-Aviv, Israel

28. Gastroenterology Department, Buenos Aires British Hospital, Argentine Catholic University (UCA), Buenos Aires, Argentina

29. Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Republic of Korea

30. Department of Medicine II, Liver Centre Munich, University Hospital, LMU Munich, Germany

31. Hepatology & Liver Intensive Care, Hospital Beaujon, Clichy, University Paris Diderot, Paris, France

32. Departamento de Medicina, Universidad de Chile Campus Centro, Hospital Clínico San Borja Arriarán, Santiago, Chile

33. Division of Gastroenterology/Hepatology, University of Miami, Miami, FL, USA

34. University of Moscow, Moscow, Russia

35. Liver Unit, Hospital Nacional Prof. Alejandro Posadas, El Palomar, Buenos Aires, Argentina

36. Department of Internal Medicine, Hallym University Kangdong Sacred Heart Hospital, Seoul, Republic of Korea

37. Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea

38. Department of Internal Medicine IV, Jena University Hospital, Jena, Germany

39. Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany

Abstract

Background and Aims: The administration of an appropriate empirical antibiotic treatment is essential in cirrhosis and severe bacterial infections. We aimed to investigate the predictors of clinical response of empirical antibiotic treatment in a prospective cohort of patients with cirrhosis and bacterial and fungal infections included in the International Club of Ascites(ICA) “Global Study” Methods: Hospitalized patients with cirrhosis and bacterial/fungal infection were prospectively enrolled at 46 centers. Clinical response to antibiotic treatment was defined according to changes in markers of infection/inflammation, vital signs, improvement of organ failure, and results of cultures. Results: From October 2015 to September 2016, 1302 patients were included at 46 centres. A clinical response was achieved only 61% of cases. Independent predictors of lack of clinical response to empirical treatment were C-reactive protein (OR=1.16;95%CI=1.02–1.31),blood leukocyte count (OR=1.39;95%CI=1.09–1.77), serum albumin (OR=0.70;95%CI=0.55–0.88), nosocomial infections (OR=1.96;95%CI=1.20–2.38), pneumonia (OR=1.75;95%CI=1.22–2.53),and ineffective treatment according to antibiotic susceptibility test (OR=5.32;95%CI=3.47-8.57). Patients with lack of clinical response to first-line antibiotic treatment had a significantly lower resolution rate of infections (55%vs. 96%;p<0.001), a higher incidence of second infections (29%vs. 15%;p<0.001),shock (35%vs. 7%;p<0.001) and new organ failures (52%vs. 19%;p<0.001) than responders. Clinical response to empirical treatment was an independent predictor of 28-day survival (sHR=0.20;95%CI=0.14-0.27). Conclusion: Four out of 10 patients with cirrhosis do not respond to the first-line antibiotic therapy, leading to lower resolution of infections and higher mortality. Broader-spectrum antibiotics and strategies targeting systemic inflammation may improve prognosis in patients with high degree of inflammation, low serum albumin levels and severe liver impairment. Lay Summary: In a large, hospitalized cohort of patients with cirrhosis and infection at 46 multinational sites, lack of clinical response to empirical antibiotics was noted in four out of each ten patients. The non-response varied according to the geographic area and prevalence of multidrug/extensively drug resistant organisms with lowest response noted in the Asian countries particularly the Indian subcontinent. Severe systemic inflammation, as indicated by high white cell count, serum C-reactive protein levels low serum albumin concentration, presence of pneumonia, nosocomial infection and ineffective treatment were independent predictors of lack of clinical response to empirical antibiotic regimens. Patients with non-response to empirical regimen had worse clinical outcomes and this was identified as an independent predictor of higher in-hospital and 28-day mortality. Additional care and novel antibiotic protocols are an unmet need in cirrhosis patients, especially those with higher degree of inflammation, lower serum albumin levels and more severe liver impairment.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Hepatology

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