12th C. L. Oakley lecture. Pathogenesis of Clostridium difficile infection of the gut.

On the basis of the above findings it is possible to propose a sequence of events following exposure to C. difficile. Exposure of neonates to C. difficile leads to transient colonisation which is almost invariably asymptomatic; the reasons why colonisation is asymptomatic are not known. Exposure of antibiotic-treated adults to C. difficile does not invariably lead to colonisation; however, in those instances where colonisation occurs, it may be transient and asymptomatic or transient and symptomatic. The transient nature of the colonisation could be because the infecting strain is poorly virulent, or because the degree of compromise of the intestinal flora is insufficient to permit establishment and full expression of virulence. It is likely that it is easier to fully compromise the intestinal flora of the elderly so that they more readily become fully susceptible to colonisation by C. difficile. In a fully susceptible host and with a highly virulent strain, the following sequence of events could occur. The organism may associate with the intestinal mucosa possible via fimbriae, and form a microcolony of capsulate cells protected by a glycocalyx. The toxins, or other factors, produced may facilitate the interaction with mucosa and toxin A will result in increased vascular and mucosal permeability resulting in intra-luminal accumulation of serum-albumin-rich fluid. Although C. difficile does not appear to be capable of using serum albumin nutritionally, it may utilise other serum proteins, and the serum proteins in general may compete with host proteases and help prevent degradation of the toxins produced.(ABSTRACT TRUNCATED AT 250 WORDS)