Extended Infusion of β-Lactams for Bloodstream Infection in Patients With Liver Cirrhosis: An Observational Multicenter Study

Author:

Bartoletti Michele1ORCID,Giannella Maddalena1,Lewis Russell E1,Caraceni Paolo2,Tedeschi Sara1,Paul Mical3,Schramm Christoph4,Bruns Tony5,Merli Manuela6,Cobos-Trigueros Nazaret7,Seminari Elena8,Retamar Pilar9,Muñoz Patricia10,Tumbarello Mario11,Burra Patrizia12,Torrani Cerenzia Maria13,Barsic Bruno14,Calbo Ester15,Maraolo Alberto Enrico16,Petrosillo Nicola17,Galan-Ladero Maria Angeles18,D’Offizi Gianpiero19,Zak-Doron Yael3,Rodriguez-Baño Jesus9,Baldassarre Maurizio220,Verucchi Gabriella1,Domenicali Marco2,Bernardi Mauro2,Viale Pierluigi1,Campoli Caterina,Pascale Renato,Stallmach Andreas,Venditti Mario,Lucidi Cristina,Ludovisi Serena,de Cueto Marina,Dolores Navarro Maria,Eduardo Lopez Cortes,Bouza Emilo,Valerio Maricela,Eworo Alia,Losito Raffaella,Senzolo Marco,Nadal Elena,Ottobrelli Antonio,Varguvic Martina,Badia Cristina,Guglielmo Borgia,Gentile Ivan,Buonomo Antonio Riccardo,Boumis Evangelo,Beteta-Lopez Alicia,Rianda Alessia,Taliani Gloria,Grieco Stefania,

Affiliation:

1. Infectious Diseases Unit, Department of Medical and Surgical Sciences, Sant’Orsola-Malpighi Hospital, University of Bologna, Italy

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

3. Unit of Infectious Diseases, Rambam Health Care Campus, HaAliya HaShniya, Israel

4. Department of Gastroenterology and Hepatology, University Clinic of Cologne, Germany

5. Department of Internal Medicine IV, Jena University Hospital, Friedrich Schiller University, Germany

6. Division of Gastroenterology, Department of Clinical Medicine, Sapienza University of Rome, Viale, Italy

7. Department of Infectious Diseases, Hospital Clínic, University of Barcelona, Spain

8. Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

9. Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen Macarena–Instituto de Biomedicina de Sevilla (IBIS) and Departamento de Medicina, Universidad de Sevilla, Madrid, Spain

10. Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain

11. Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy

12. Multivisceral Transplant Unit, Department of Surgery, Oncology, and Gastroenterology, Padova University Hospital, Italy

13. Gastrohepatology Unit, AOU Città della Salute e della Scienza di Torino, University of Turin, Italy

14. Infectious Diseases, University Hospital for Infectious Diseases “Dr Fran Mihaljevic,” Zagreb, Croatia

15. Infectious Disease Unit, Service of Internal Medicine, Hospital Universitari Mútua de Terrassa, Barcelona, Spain

16. Department of Clinical Medicine and Surgery, Section of Infectious Diseases, University of Naples Federico II

17. 2nd Infectious Diseases Division, National Institute for Infectious Diseases L. Spallanzani, Rome

18. Clinical Microbiology, Nuestra Senora del Prado Hospital, Rome

19. Hepatology and Infectious Diseases Unit, National Institute for Infectious Diseases L. Spallanzani, Rome

20. S.Orsola-Malpighi University Hospital, Center for Applied Biomedical Research, Bologna, Italy

Abstract

Abstract Background We analyzed the impact of continuous/extended infusion (C/EI) vs intermittent infusion of piperacillin-tazobactam (TZP) and carbapenems on 30-day mortality of patients with liver cirrhosis and bloodstream infection (BSI). Methods The BICRHOME study was a prospective, multicenter study that enrolled 312 cirrhotic patients with BSI. In this secondary analysis, we selected patients receiving TZP or carbapenems as adequate empirical treatment. The 30-day mortality of patients receiving C/EI or intermittent infusion of TZP or carbapenems was assessed with Kaplan-Meier curves, Cox-regression model, and estimation of the average treatment effect (ATE) using propensity score matching. Results Overall, 119 patients received TZP or carbapenems as empirical treatment. Patients who received C/EI had a significantly lower mortality rate (16% vs 36%, P = .047). In a Cox-regression model, the administration of C/EI was associated with a significantly lower mortality (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.11–0.936; P = .04) when adjusted for severity of illness and an ATE of 25.6% reduction in 30-day mortality risk (95% CI, 18.9–32.3; P < .0001) estimated with propensity score matching. A significant reduction in 30-day mortality was also observed in the subgroups of patients with sepsis (HR, 0.21; 95% CI, 0.06–0.74), acute-on-chronic liver failure (HR, 0.29; 95% CI, 0.03–0.99), and a model for end-stage liver disease score ≥25 (HR, 0.26; 95% CI, 0.08–0.92). At competing risk analysis, C/EI of beta-lactams was associated with significantly higher rates of hospital discharge (subdistribution hazard [95% CI], 1.62 [1.06–2.47]). Conclusions C/EI of beta-lactams in cirrhotic patients with BSI may improve outcomes and facilitate earlier discharge.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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