Clostridium difficile 30 years on: what has, or has not, changed and why?

The report of clindamycin-associated colitis in 1974 by Tedesco et al. [Ann Intern Med 81: 429–33] stimulated an intense search for the cause of this severe complication of antibiotic use. The search culminated in early 1978 in the publication of a series of papers within 3 months that identified the causative agent as Clostridium difficile and its accompanying toxins. Thirty years later we are in the midst of a resurgence of C. difficile infection (CDI) in North America and Europe that is greater than ever previously reported and for which morbidity and mortality appear to be higher than ever seen in the past. The purpose of this review is to highlight the discoveries of the past 30 years that, in my view, have brought us to our current level of understanding of the pathogenesis, prevention and treatment of CDI, and to suggest why a disease thought to be managed so well 30 years ago could now be causing more morbidity and mortality than ever before. In the 21st century the focus should be on better understanding the relationship between the C. difficile organism and the host at the mucosal level, so that biotherapeutic and vaccine strategies for the prevention of CDI can be developed.