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

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:

1. Lactic acid bacteria and fermentable fiber
2. Fermentable fiber alone
3. 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.