Antibiotic therapy and Clostridium difficile infection – primum non nocere – first do no harm Grace S Crowther,1 Mark H Wilcox1,2 1Faculty of Medicine and Health, University of Leeds, Leeds, UK; 2Department of Microbiology, Leeds Teaching Hospitals Trust, Leeds, UK Abstract: Treatment options for Clostridium difficile infection (CDI) remain limited despite this usually nosocomial infection posing an urgent threat to public health. A major paradox of the management of CDI is the use of antimicrobial agents to treat infection, which runs the risk of prolonged gut microbiota perturbation and so recurrence of infection. Here, we explore alternative CDI treatment and prevention options currently available or in development. Notably, strategies that aim to reduce the negative effects of antibiotics on gut microbiota offer the potential to alter current antimicrobial stewardship approaches to preventing CDI. Keywords: treatment, prevention, CDI, SYN-004, vaccine, beta-lactams