Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection

Abstract

Proton pump inhibitors (PPIs) have been associated with Clostridium difficile infection (CDI) in several recent studies. However, other studies have not shown this association, and the mechanism by which PPIs might promote CDI has not been elucidated. We hypothesized two possible mechanisms of causation: first, by raising pH, PPIs may prevent gastric contents from killing C. difficile spores; second, gastric contents of PPI-treated patients may promote germination and outgrowth of C. difficile spores. Survival rates of spores from six different strains of C. difficile in acidic gastric contents were assessed using quantitative cultures on selective media. Germination and outgrowth of spores were assessed by heat shock at 80°C, phase-contrast microscopy, and ethanol shock after incubation for 24 h in the gastric contents of patients and in the gastric, small intestinal, and cecal contents of mice. C. difficile spores survived and remained dormant in nonbilious gastric contents with acidic pH. Germination did not occur in unmodified gastric contents of patients but did occur with the addition of taurocholic acid and amino acids. In mice, germination did not occur in gastric contents but did occur in small intestinal and cecal contents. In summary, C. difficile spores survived in acidic gastric contents and did not undergo germination and outgrowth in gastric contents, probably due to lack of essential germinants, such as taurocholic acid. Our results suggest that the effects of PPIs in the stomach do not contribute to the pathogenesis of CDI.

Emergence of community-acquired Clostridium difficile infection: the experience of a French hospital and review of the literature

“…Hence, the use of PPIs was the main risk factor for CA-CDI. PPIs modify intestinal pH, nevertheless the origin of the association between PPI and CDI remains unclear (Nerandzic et al) 23 . Therefore, like antibiotics, PPIs may also perturb the intestinal microbiota, which favors the emergence of C. difficile.…”

Clostridium Difficile Infection in Older Adults

“…Interestingly, gastric acid suppression does not appear to increase the risk of severe or recurrent C. difficile infection [33]. In the nearly 10 years that have elapsed since identification of gastric acid suppression as a risk factor, the mechanisms for this association remain unknown [34,35]. …”

Infecciones causadas por Clostridium difficile: una visión actualizada

“…Sin embargo, se han comunicado casos en que el suministro de una dosis única de antibacterianos con fi nes profi lácticos es sufi ciente para gatillar un cuadro de IACD 88 . Con respecto al papel de los inhibidores de bomba de protones, e xiste controversia, con estudios que muestran resultados antagónicos 89,90 , por lo que claramente se necesitan más estudios para defi nir las implicancias de los inhibidores de bomba de protones en IACD.…”