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

May 28, 2015 updated by: Manuela Merli, University of Roma La Sapienza

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

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

96

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Rome, Italy, 00100
        • Recruiting
        • Manuela Merli
        • Contact:
        • Contact:
        • Principal Investigator:
          • Manuela Merli, Prof

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • HIV
  • patients underwent to liver transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Tienam
Drug: Vancomycin
Second line therapy
Other Names:
  • Vancocyn
Drug: azithromycin
Second line therapy
Other Names:
  • 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 Names:
  • Zithromax
Drug: Cefotaxime
Standard antibiotic therapy
Drug: Amoxicillin
Standard therapy
Other Names:
  • Augmentin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Efficacy of anti-multiresistant empirical antibiotic therapy in healthcare associated infections in cirrhosis
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Roma La Sapienza

Investigators

  • Principal Investigator: Manuela Merli, Prof, Gastroenterology
  • Study Chair: Claudio Puoti, Prof, Department of Medicine Epatologica Marino Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2012

Primary Completion (Actual)

May 1, 2015

Study Completion (Anticipated)

June 1, 2015

Study Registration Dates

First Submitted

October 16, 2012

First Submitted That Met QC Criteria

March 22, 2013

First Posted (Estimate)

March 28, 2013

Study Record Updates

Last Update Posted (Estimate)

May 29, 2015

Last Update Submitted That Met QC Criteria

May 28, 2015

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Infection and Cirrhosis

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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