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Empirical vs 2nd Line Antibiotic Therapy in Health-care Associated Infections in Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01820026
Recruitment Status : Unknown
Verified May 2015 by Manuela Merli, University of Roma La Sapienza.
Recruitment status was:  Recruiting
First Posted : March 28, 2013
Last Update Posted : May 29, 2015
Information provided by (Responsible Party):
Manuela Merli, University of Roma La Sapienza

Brief Summary:

Bacterial infections are a frequent complication in liver cirrhosis with a bad prognosis. However, the clinical outcome of cirrhotic patients with serious infections is significantly improved over the last 30 years due to early diagnosis and to the use of a more appropriate antibiotic therapy.

As in the general population, empirical treatment should be initiated soon after diagnosis, after making the necessary sampling and should be based on the use of an antibiotic with low toxicity and broad spectrum antibacterial efficacy, taking into account the local epidemiology and prevalence of antibiotic resistance.

The third generation cephalosporins are considered the gold standard in the treatment of most infections in cirrhotics due to their effectiveness against enterobacteriaceae and against non-enterococcal streptococci and due to their low toxicity.

However, the recommendations for the antibiotic therapy are currently based on results of trials of '80s and '90s, when the proportion of resistant pathogens was lower. Similarly to nosocomial infections, the increasing rate of infections due to multidrug resistant (MDR) bacteria represents the rational for a different choice of empirical antibiotic therapy with a higher resistance barrier. This change in the epidemiology of community acquired infections is mainly due to the increased contacts with healthcare system of these patients and for the larger use of antibiotic prophylaxis. With this regard, it was recently proposed to introduce a third epidemiological class of infection "Health care-associated": Infections occurring in community in patients who have been in contact with the health system shortly before the infection.

This epidemiological class of infection should be distinguished from "community-acquired" because they are more similar to"nosocomial" in terms of their sensitivity to antibiotics. Therefore for this class should be taken into consideration the use of a different empirical antibiotic therapy.

The investigators aim was to evaluate prospectively the effectiveness of a broad spectrum antibiotic treatment in a cohort of cirrhotic patients with "healthcare-Associated"infections

Cirrhotic patients with "Healthcare Associated" admitted to the gastroenterology department of the Policlinico Umberto I and in the Department of Hepatology of the Hospital of Marino will be consecutively enrolled.

Randomized controlled trial with randomisation stratified by epidemiological class of infection.

Condition or disease Intervention/treatment Phase
Cirrhosis Drug: Imipenem Drug: Vancomycin Drug: azithromycin Drug: Cefotaxime Drug: Amoxicillin Phase 4

Detailed Description:

Unblinded randomized controlled trial with randomisation stratified by epidemiological class of infection.

After obtaining informed consent at enrollment, participants will undergo medical examination with a detailed anamnesis and will begin collecting data on the following parameters:

  • Demographic characteristics (age, sex, etiology of cirrhosis, when the diagnosis was made).
  • Severity of liver disease(defined by the Child-Pugh classification, MELD score), indices of renal function and serum electrolytes.
  • APACHE score in the case of development of sepsis
  • Compensated cirrhosis / decompensated cirrhosis
  • If decompensated, will be listed complications (ascites, esophageal-gastric varices, hepatic encephalopathy, coagulopathy, Hepato-Renal Syndrome, variceal bleeding).
  • Treatment and dosage (eg β-blockers, diuretics)
  • Hemodynamic parameters (heart rate / blood pressure)

Patients enrolled will be randomized and treated with conventional therapy provided for community-acquired infections or with the "2nd line antibiotic therapy", based on use of of imipenem-cilastatin.

The protocol of antibiotic therapy chosen for this category of patients will be based on a antibiotic class recommended for a specific site of infection in international guidelines for the treatment of nosocomial infections and / or healthcare associated with a high safety profile and is already used in the investigators hospital. The cost of empirical treatment with imipenem / cilastatin is roughly comparable to that with the currently used first-line antibiotics for such infections, and frequently used drugs in the forefront of these patients are ineffective is therefore necessary to embark on a new antibiotic with higher costs also in terms of days of hospitalization.

During the hospitalization will be recorded the type of infection, empirical therapy, its duration, side effects, isolated pathogens and their resistance, when available, the occurrence of complications related to infection and mortality.

The efficacy of therapy will be assessed based on the resolution of infection attested by normalization of clinical , biochemical and microbiological parameters and the instrumental tools.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 96 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Bacterial Infections Associated With Healthcare (Healthcare-Associated) in Hospitalized Cirrhotic Patients: Randomized Study of Use of Traditional Empirical Antibiotic Therapy and Second-line Targeted at Multi-resistant Bacteria
Study Start Date : December 2012
Actual Primary Completion Date : May 2015
Estimated Study Completion Date : June 2015

Arm Intervention/treatment
Experimental: Imipenem & Vancomycin & Azithromycin

Tienam combined with vancomycin (1g/12 h) for Spontaneous bacterial peritonitis, cholangitis, sepsis without evidence of a source of infections.

Tienam combined with vancomycin (1g/12 h)and azythromycin (500 mg/24 h)for pneumonia

Drug: Imipenem
second line therapy
Other Name: Tienam

Drug: Vancomycin
Second line therapy
Other Name: Vancocyn

Drug: azithromycin
Second line therapy
Other Name: Zithromax

Active Comparator: Cefotaxime & Amoxicillin & Azithromycin
Cefotaxime IV(2g/12 h): for Spontaneous bacterial peritonitis, cholangitis, sepsis without evidence of specific site of infection Amoxicillin/clavulanic acid (2,2 g/8 h)or Ciprofloxacin (500 mg/12 h: urinary tract infections Amoxicillin/clavulanic acid (2,2 g/8 h)and azithromycin (500 mg/24 h): pneumonia Amoxicillin/clavulanic acid (2,2 g/8 h)for skin or soft tissue infection
Drug: azithromycin
Second line therapy
Other Name: Zithromax

Drug: Cefotaxime
Standard antibiotic therapy

Drug: Amoxicillin
Standard therapy
Other Name: Augmentin

Primary Outcome Measures :
  1. Efficacy of anti-multiresistant empirical antibiotic therapy in healthcare associated infections in cirrhosis [ Time Frame: 1 year ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • cirrhosis
  • healthcare infection
  • older than 18 years
  • agreement to participate

Exclusion Criteria:

  • HIV
  • patients underwent to liver transplantation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01820026

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Contact: Manuela Merli, Prof 00390649972001
Contact: Cristina Lucidi, Dr 00393395263376

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Manuela Merli Recruiting
Rome, Italy, 00100
Contact: Manuela Merli, Prof    00300649972001   
Contact: Cristina Lucidi, Dr    00393395263376   
Principal Investigator: Manuela Merli, Prof         
Sponsors and Collaborators
University of Roma La Sapienza
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Principal Investigator: Manuela Merli, Prof Gastroenterology
Study Chair: Claudio Puoti, Prof Department of Medicine Epatologica Marino Hospital
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Manuela Merli, Prof, University of Roma La Sapienza Identifier: NCT01820026    
Other Study ID Numbers: Infection and Cirrhosis
First Posted: March 28, 2013    Key Record Dates
Last Update Posted: May 29, 2015
Last Verified: May 2015
Keywords provided by Manuela Merli, University of Roma La Sapienza:
healthcare infection cirrhosis antibiotic
Additional relevant MeSH terms:
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Liver Cirrhosis
Pathologic Processes
Liver Diseases
Digestive System Diseases
Amoxicillin-Potassium Clavulanate Combination
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action