Empirical vs 2nd Line Antibiotic Therapy in Health-care Associated Infections in Cirrhosis
Information source: University of Roma La Sapienza
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cirrhosis
Intervention: Imipenem (Drug); Vancomycin (Drug); azithromycin (Drug); Cefotaxime (Drug); Amoxicillin (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: University of Roma La Sapienza Official(s) and/or principal investigator(s): Manuela Merli, Prof, Principal Investigator, Affiliation: Gastroenterology Claudio Puoti, Prof, Study Chair, Affiliation: Department of Medicine Epatologica Marino Hospital
Overall contact: Manuela Merli, Prof, Phone: 00390649972001, Email: clucidi@hotmail.it
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.
Clinical Details
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 design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Efficacy of anti-multiresistant empirical antibiotic therapy in healthcare associated infections in cirrhosis
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- cirrhosis
- healthcare infection
- older than 18 years
- agreement to participate
Exclusion Criteria:
- HIV
- patients underwent to liver transplantation
Locations and Contacts
Manuela Merli, Prof, Phone: 00390649972001, Email: clucidi@hotmail.it
Manuela Merli, Rome 00100, Italy; Recruiting Manuela Merli, Prof, Phone: 00300649972001, Email: clucidi@hotmail.it Cristina Lucidi, Dr, Phone: 00393395263376, Email: clucidi@hotmail.it Manuela Merli, Prof, Principal Investigator
Additional Information
Starting date: December 2012
Last updated: May 28, 2015
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