Proton Pump Inhibitors and Clostridium Difficile Infection: Are We Propagating an Already Rapidly Growing Healthcare Problem?

Abstract

Proton pump inhibitors (PPIs) have been associated with Clostridium difficile infection (CDI) in several recent studies. The exact mechanism through which PPIs may cause Clostridium difficile infection is not well understood. One potential mechanism to explain this association may be that elevated gastric pH levels facilitate the growth of potentially pathogenic upper and lower gastrointestinal tract flora. Although Clostridium difficile spores are acid resistant, vegetative forms are susceptible to acidity. Higher gastric PH therefore increases vegetative bacteria counts in the small and large intestine. Other potential mechanisms include impairment of leukocytes and other immune responses and antimicrobial properties of PPIs. In recent years, much research has been contributed to prove the relationship between PPIs and CDI as causal. Most studies however, fail to prove causality due to the use of antibiotics and other medications during time of initial diagnosis of CDI. PPIs continue to also be one of the most heavily prescribed drugs in our country. As primary and recurrent infection caused by Clostridium difficile continues to rise, more data must be collected to determine better treatment, overall management, and the role that PPIs may play in its propagation.

Fecal Microbiota Transplantation in Patients With Recurrent Clostridium difficile Infection: A Four-Year Single-Center Retrospective Review

“…This makes being on immunosuppressants an independent risk factor for recurrent CDI as shown in a previous study [15]. In the past few years, multiple studies and meta-analysis have shown a significant relationship between PPI use and the risk of CDI while some studies have rejected this hypothesis [16][17][18]. Our study did not show a causal relationship between PPI use and recurrence of CDI.…”

Proton pump inhibitors: An incisive review

“…The use of proton pump inhibitors has also been linked to the development of microscopic colitis. 16,17 8. Cardiovascular PPI use and cardiovascular events have also been researched extensively, but no firm conclusions have been reached because these relative risks are masked by other factors.…”

Prevention of Clostridium difficile Infection in Critically Ill Adults

“…51 Proposed mechanisms include the promotion of intestinal pathogen growth related to elevated gastric pH, impairment of leukocytes, inhibition of the protective effect of gastric acid on proliferation of C. difficile spores, or specific antimicrobial properties of proton pump inhibitors (PPIs). 52 Data related to specific gastric acid-suppressing agents and CDI risk are conflicting. In 2014, a large retrospective study of ICU patients found that PPI therapy was independently associated with CDI and that the risk of CDI was higher with PPIs versus histamine 2 receptor antagonists (3.8% vs 2.2%, respectively, p<0.01).…”

“…Although meta‐analyses have suggested an association between gastric acid suppression and both primary and recurrent CDI risk, the exact mechanism to explain this increased risk remains unclear . Proposed mechanisms include the promotion of intestinal pathogen growth related to elevated gastric pH, impairment of leukocytes, inhibition of the protective effect of gastric acid on proliferation of C. difficile spores, or specific antimicrobial properties of proton pump inhibitors (PPIs) . Data related to specific gastric acid–suppressing agents and CDI risk are conflicting.…”