The Role of Synbiotics in Reducing Post-Operative Infections in Patients Undergoing Cardiac Surgery: A Pilot Study

October 30, 2007 updated by: Beth Israel Medical Center

All surgical procedures carry with them the risk of infection. Even a minor infection can extend the hospitalization after cardiac surgery. The average minimum increase in length of stay for a single infection is three days.

One of the many means used to reduce post-operative infections is the preventative, or "prophylactic", administration of antibiotics just before and just after surgery. Because antibiotics, and for that matter surgery itself, alter the body's natural immune and inflammatory responses and the makeup of the bacteria in the intestine, there is a great deal of scientific interest in using the supplementation of bacteria that naturally reside in the intestine. It is felt that by doing so, the alterations in the immune response may be corrected and the patient better able to fight infections. There are studies using probiotics that have demonstrated a reduction in infection rates in patients undergoing abdominal surgery.

Subjects will be patients at high risk for infection including those with any one or more of the following characteristics: over 65 years old, poor heart function (ejection fraction <40), diabetes (insulin dependant or non-insulin dependant), peripheral vascular disease, kidney dysfunction (creatinine level >2mg/dl), obesity (body surface area > 2 m2), low serum protein levels (albumin < 2.5 mg/dl), infection of the heart valve (endocarditis), or on any antibiotics other than standard prophylaxis before surgery.

The safety of these products has been very well established.

Patients who consent to enter the study will receive the synbiotic mix, or a placebo, which comes in a powder that may be mixed with a drink, or washed down into the stomach through the NG tube if the patient is still on a ventilator. Dosing will be initiated within four hours of patient arrival in the Cardiac Surgery Intensive Care Unit and will continue on a twice daily basis for the duration of their admission days. Infection and diarrhea data will be monitored.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Drug: Synbiotic 2000

Detailed Description

Background:

Despite progress in surgical methodology, infections remain one of the most difficult post-operative complications to prevent. In cardiac surgery, the presence of an infection can make the difference between a brief hospital stay and a life-threatening illness. The average minimum increase in length of stay due to a single infection is three days and can extend to months. Nationally, the average rate of deep sternal wound infection is 3% and conduit harvest site infection 1.4%.

Because of the intimate relationship between intestinal bacterial flora and normal gut and immunologic function, current research is investigating the relationship between the preservation or augmentation of certain naturally occurring bacterial strains in the intestine and clinical outcomes, particularly infectious. We propose to examine the efficacy of immediate post-operative supplementation with a product containing four bacterial strains and four different fibers, putatively fuel for bacterial growth, in reducing infections.

Until recently, most studies performed with LAB have selected strains for their palatability and usability in yogurts. For this reason, most studies have been based on LAB, such as Lactobacillus acidophilus, L.casei, L. delbrueckii och Bifidobacillus adolescentis, B.bifidum, B.longum and Bifidobacterium infantis, which are common in yogurts and kefirs. It is only recently that interest has been focused on developing criteria for selecting LAB based on intraluminal biology, such as the ability to adhere to mucus or mucosal cells, the ability to ferment resistant fibers, and antioxidant capacity. For example, L.plantarum, which is often recovered from fermented fruits, vegetables, sourdoughs and silage, has been demonstrated to have a strong ability to adhere to mucosa and to break down resistant fibers. L. plantarum is the commonest LAB in human gastrointestinal tract and has shown the greatest ability of all LAB tested to survive in the gut (106 times that of L.rhamnosus for example) and activate cytokine secretion after passage through the stomach and the small intestine.

The clinical impact of a particular LAB is strongly associated with its ability to colonize the intestinal mucosa. LAB common in dairy products such as yogurts (L.Acidophilus, L.bulgaris and bifidobacteria) have very limited ability to colonize intestinal mucosal cells. L.rhamnosus (GG) and even more so L.plantarum (299) have been shown to remain viable up to 28 days post supplementation. L.plantarum is unique as it uses carbohydrate receptors (mannose) similar to those of gram-negative bacteria (E.coli, Enterobacter, Klebsiella, Salmonella, Shigella, Pseudomonas and Vibrio cholerae). L. plantarum has also been shown to prevent adhesion of enteropathogenic E.coli through induction of mRNA expression for the intestinal mucins MUC2 and MUC3.

Design of the present study 75 consecutive patients deemed at high risk for post-operative infection will be prospectively and blindly randomized to one of the following three groups:

Lactic acid bacteria and fermentable fiber
Fermentable fiber alone
Non-fermentable (placebo)

Sachets containing LAB plus fiber, fiber alone, or placebo will be provided by the manufacturer and will be randomized, coded, and assigned to patients in order. Patients will begin receiving doses within 4 hours of arrival to the CSICU and will remain on treatment twice daily for 14 days.

Data collection Infection control data are collected on all patients undergoing cardiac surgery using established institutional definitions for infections. Incidence of sternal infections, donor site infections, vein harvest site infection, pneumonia, urinary tract infection, catheter and blood stream infections, and clostridium difficile colitis will be considered. In addition, the incidence of diarrhea, defined as stools of liquid or gelatinous consistency, or more than three stools in one day, will be monitored. Data will be collected during hospital stay and at one-month follow-up. Finally, C-reactive protein levels, which are commonly assessed during hospitalizations and used as part of the assessment for coronary risk, will be drawn pre-operatively and four days post-operatively.

Study Type

Interventional

Enrollment (Actual)

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 Locations

United States
- New York
  - New York, New York, United States, 10003
    - Beth Israel Medical Center

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

Child
Adult
Older Adult

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Undergoing cardiac surgery, able to consent, and at least one of the following:
- Age >65 years
- ejection fraction <=40%
- diabetes mellitus (insulin requiring and non-insulin requiring)
- peripheral vascular disease
- creatinine >=2 mg/dl
- body surface area >= 2 sq meters
- endocarditis
- albumin <=2.5 g/dl
- on antibiotics for any reason other than operative prophylaxis

Exclusion Criteria:

Unable to consent
Not meeting inclusion criteria

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: Prevention
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Quadruple

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Infection Time Frame: 3 months	3 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Tolerance Time Frame: 2 weeks	2 weeks

Collaborators and Investigators

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

Sponsor

Beth Israel Medical Center

Investigators

Principal Investigator: David S Seres, MD, Beth Israel Medical Center

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

November 1, 2005

Study Completion (Actual)

June 1, 2007

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria