Abstract

Background: Intravenous immunoglobulin (IVIG) has been used for many years as an adjunct to treat severe and recurrent Clostridium difficile infection. The concentration of serum antibodies to toxins A and B have been shown to correlate with an asymptomatic carrier state in patients with C. difficile colonization. Furthermore, the lack of development of an effective humoral response to C. difficile toxins may result in increased risk of development of recurrent infection. Objective: Studies of IVIG treatment for C. difficile infection have been inconclusive. We therefore sought to examine whether the effectiveness of IVIG therapy could be altered by variability in anti-toxin antibody content in commercial preparations of IVIG. Methods: Antibodies against C. difficile toxins A and B were measured by ELISA in eight commercially-available immunoglobulin preparations. These preparations represent those that are commonly available for IVIG therapy and included two products that have high titers of antibodies against cytomegalovirus (CMV) and respiratory syncytial virus (RSV). Results: Different preparations of IVIG demonstrated approximately a fourfold variability in antibody content against toxin A and toxin B. Preparations that are formulated to contain high-titers of antibodies against CMV and RSV did not contain higher titers of antibody against C. difficle toxins over standard IVIG preparations. Conclusions: Currently-utilized preparations of immunoglobulin, used as IVIG in the treatment of C. difficile colitis show substantial variability in their anti-C. difficile toxin A and B titers. The ability of these preparations to neutralize toxin effect may be affected by anti-toxin titers and this variability may contribute to variations in the published literature with regard to efficacy of IVIG in severe and recurrent C. difficile colitis.

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