Is over-use of proton pump inhibitors fuelling the current epidemic of Clostridium difficile-associated diarrhoea?

Many developed countries have seen an increase in cases of Clostridium difficile-associated diarrhoea (CDAD) in recent years. This has occurred despite heightened awareness of the risks of broad-spectrum antibiotics, overall reduction in antibiotic use and increased focus on hospital hygiene. Some of the increase is due to the introduction of new hypervirulent strains, but it predates the description of these. The epidemic coincides with increased use of proton pump inhibitors (PPIs), much of which is inappropriate according to UK and other national guidelines. Gastric acid is a key host defence against other gastrointestinal infections and epidemiological and animal studies have demonstrated a positive association between incident CDAD and PPI use. An association with recurrence of CDAD after initially successful treatment has also been found. Vegetative C. difficile cells are rapidly killed at normal gastric pH, but survive at the pH found in patients taking PPI. It has recently been shown that vegetative organisms survive long enough on moist surfaces for transmission between patients to occur. We conclude that restricting PPI use to patients with an appropriate indication would reduce unnecessary expenditure on these agents, and might be an additional means of controlling the current epidemic of CDAD.