Monoclonal antibodies against Clostridium difficile infection in the pipeline

The increasing incidence and severity of Clostridium difficile infection (CDI) is becoming a major issue in public health. The identification of new therapeutic options able to control severe cases and reduce the risk of recurrence is a research priority. Toxins A (TcdA) and B (TcdB) and host immune response are the major determinants of CDI pathogenesis and may be a possible target for new therapies. The aim of this review was to critically describe the evidence available on the effect of monoclonal antibodies (MAbs) on CDI, putting them into clinical context and highlighting possible advantages and barriers to their use. Experimental animal studies revealed the potential of MAbs to protect against CDI progression and recurrence, especially when a combination of anti-TcdA and anti-TcdB is used. Only one clinical trial confirmed that this combined approach is well tolerated and effective in controlling CDI recurrences in at-risk subjects with refractory CDI. Other clinical trials are currently ongoing and explore alternative molecules. Toxin-targeted MAbs are one of the most promising approaches and at-risk subjects and those experiencing recurrence are the ideal targets for this second-line treatment. However, CDI epidemiology is rapidly changing and MAbs may also represent a powerful option for other patients.