Anti-C. difficile Toxin B Monoclonal antibody

C. difficile infection (CDI) is an important healthcare-but also community-associated disease. CDI is considered a public health threat and an economic burden. A major problem is the high rate of recurrences. Besides classical antibiotic treatments, new therapeutic strategies are needed to prevent infection, to treat patients and prevent recurrences. If fecal transplantation has been recommended to treat recurrences, another key approach is to restore immunity against C. difficile and its virulence factors. Here, after a summary concerning the virulence factors, the host immune response against C. difficile and its role in the outcome of disease, we review the different approaches of passive immunotherapies and vaccines developed against CDI. Passive immunization strategies are designed in function of the target antigen, the antibody-based product and its administration route. Similarly, for active immunization strategies, vaccine antigens can target toxins or surface proteins and immunization can be performed by parenteral or mucosal routes. For passive immunization and vaccination as well, we first present immunization assays performed in animal models and second in humans and associated clinical trials. The different studies are presented according to the mode of administration either parenteral or mucosal and the target antigens, either toxins or colonization factors.

Background and Aim: Clostridium difficile is a major cause of health care-associated infection, but disagreement between diagnostic tests is an ongoing barrier to clinical decision-making. Conventional enzyme immunoassay (EIA) for toxin detection is currently the most frequently used technique for C.difficile infection (CDI) diagnosis, but its low sensitivity makes the development of an alternative strategy necessary for improving the diagnosis in developing countries. Methods: Between years 2011 and 2015, 154 stool samples from patients with antibiotic-associated diarrhea were examined by toxigenic culture and EIA for the diagnosis of CDI. In the year 2015, when glutamate dehydrogenase (GDH) test was first available in Brazil, 53 of those fecal specimens were also tested by the C. diff Quik Chek Complete rapid immunoassay. At this time, we prospectively assessed the impact of this test on CDI treatment rates before and after it was introduced in clinical practice. Results: The GDH component of C. diff Quik Chek Complete test had a sensitivity of 100% and specificity of 95.1% compared with toxigenic culture, with 89.8% concordance. The Tox A/B II EIA and the toxin portion of C. diff Quik Chek Complete yielded sensitivities between values of 50-58.3%, with 100% specificities. The introduction of GDH test increased the number of treated patients with CDI from 57.7% to 100%. Conclusions: Glutamate dehydrogenase test is a reliable method for the diagnosis of CDI and greatly increases the number of properly treated patients with CDI. Therefore, this exam should be considered the mainstay for the laboratory diagnosis of CDI in developing countries.