Proton Pump Inhibitors Do Not Increase Risk for Clostridium difficile Infection in the Intensive Care Unit

Abstract

Objectives Patients in the intensive care unit (ICU) frequently receive proton pump inhibitors (PPIs) and have high rates of Clostridium difficile infection (CDI). PPIs have been associated with CDI in hospitalized patients, but ICU patients differ fundamentally from non-ICU patients and few studies have focused on PPI use exclusively in the critical care setting. We performed a retrospective cohort study to determine the associations between PPIs and healthcare facility–onset CDI in the ICU. Methods We analyzed data from all adult ICU patients at three affiliated hospitals (14 ICUs) between 2010–2013. Patients were excluded if they had recent CDI or an ICU stay of <3 days. We parsed electronic medical records for ICU exposures, focusing on PPIs and other potentially modifiable exposures that occurred during ICU stays. Healthcare facility–onset CDI in the ICU was defined as a newly positive PCR for the C. difficile toxin B gene from an unformed stool, with subsequent receipt of anti-CDI therapy. We analyzed PPIs and other exposures as time-varying covariates and used Cox proportional hazards modeling to adjust for demographics, comorbidities, and other clinical factors. Results Of 18,134 patients who met criteria for inclusion, 271 (1.5%) developed healthcare facility–onset CDI in the ICU. Receipt of antibiotics was the strongest risk factor for CDI (adjusted HR (aHR) 2.79; 95% confidence interval (CI), 1.50–5.19). There was no significant increase in risk for CDI associated with PPIs in those who did not receive antibiotics (aHR 1.56; 95% CI, 0.72–3.35), and PPIs were actually associated with a decreased risk for CDI in those who received antibiotics (aHR 0.64; 95% CI, 0.48–0.83). There was also no evidence of increased risk for CDI in those who received higher doses of PPIs. Conclusions Exposure to antibiotics was the most important risk factor for healthcare facility–onset CDI in the ICU. PPIs did not increase risk for CDI in the ICU regardless of use of antibiotics.

Prophylaxis for Stress Ulcers With Proton Pump Inhibitors Is Not Associated With Increased Risk of Bloodstream Infections in the Intensive Care Unit

“…Along with previous studies, these data suggest that PPIs do not meaningfully alter clinical outcomes with respect to some of the most important ICU infections: bloodstream infections, VAP, or Clostridium difficile infection. 35 In the ICU setting, any effects of PPIs may simply be too subtle or too short-lived to exert a downstream effect on risk for BSI or other infections.…”

Evaluation of Risk Factors forClostridium difficileInfection in Hematopoietic Stem Cell Transplant Recipients

“…It has been hypothesized that PPIs alter the colonic flora by facilitating the growth of potentially pathogenic organisms in the gastrointestinal tract . A few studies reported no increased risk of developing CDI if patients are exposed to a PPI . However, significantly more clinical studies found the use of a PPI among hospitalized patients as a risk factor for the development of CDI …”

Clostridium Difficile Infection - An Optimistic View

“…While most studies suggest a higher risk for CDI during PPI treatment, there are contradictory reports in literature [19]. Given that acid suppression drugs may be over-prescribed in surgical settings, consideration should be given to stopping PPIs in patients at high risk of CDI [8].…”

“…The prophylactic dose given immediately before surgery is associated with dramatically reduced rates of wound infection and post-operative sepsis [18]. It is likely that any slightly increased risk of post-operative CDI associated with such prophylactic use of antibiotics would be outweighed by benefit [8].While most studies suggest a higher risk for CDI during PPI treatment, there are contradictory reports in literature [19]. Given that acid suppression drugs may be over-prescribed in surgical settings, consideration should be given to stopping PPIs in patients at high risk of CDI [8].…”