P-167 Serum Derived Bovine Immunoglobulin Enhances Overall Survival of Clostridium Difficile Associated Disease Accentuated by Malnutrition

Abstract

The morbidity, mortality and financial costs of Clostridium difficile infection (CDI) have increased dramatically over the past decade. The primary virulence factors are toxins A and B. Risk factors for CDI include antibiotics, ages over 65, inflammatory bowel disease, gastrointestinal surgery and malnutrition. Serum-derived bovine immunoglobulin (SBI) is predominantly IgG and has been shown to bind and neutralize toxins A and B in vitro. Based on these results, we hypothesized that SBI would reduce mortality in an in vivo mouse model of CDI. Mice on a 5% protein (low, 25% of protein requirement by N.R.C.) or 20% protein (normal) diet were provided 40 mg/day SBI or hydrolyzed collagen (HC) in drinking water/oral gavage for the entire study. On day -5 a cocktail of antibiotics was orally administered for 3 days followed by parenteral clindamycin on day -1. Mice were challenged with 105 CFU C. difficile on day 0 and treated with vancomycin from days 0–4. Kaplan-Meier survival curves were generated. Overall, mice administered SBI had a significant reduction in CDI-associated mortality compared to HC-treated mice (P = 0.002). While the difference in survival when comparing SBI and HC in normal protein diets was not significant (P = 0.13), mice fed a low protein diet and SBI were substantially protected against mortality as shown in Figure 1 (P = 0.005). These results indicate that SBI is particularly effective at reducing CDI mortality in a state of malnutrition. Future studies will focus on how SBI and the interaction of malnutrition, affect colonization and resistance of C. difficile.