A Vanished Association Between Proton Pump Inhibitors and Clostridioides Difficile Infection After Minimizing Bias

Area of Science:

• Pharmacovigilance
• Gastroenterology
• Infectious Diseases

Background:

• Proton-pump inhibitors (PPIs) may influence the gut microbiome, potentially increasing Clostridioides difficile infection (CDI) risk.
• The association between PPI use and CDI remains a subject of ongoing debate and investigation.

Purpose of the Study:

• To reevaluate the association between PPIs and CDI using pharmacovigilance data.
• To account for and investigate the impact of competition bias, particularly from antibacterial drugs, on the PPI-CDI association.

Main Methods:

• Analysis of Food and Drug Administration adverse event reports (2004-2023) for PPI-related CDI.
• Disproportionality analysis using Reporting Odds Ratio (ROR) and Information Component (IC).
• Quantitative assessment of competition bias and age-stratified analyses to control for confounding factors.

Main Results:

• Initial analysis showed a significant association between PPIs and CDI (ROR=2.36).
• After adjusting for antibacterial drug co-exposure, the CDI signal strength significantly decreased, implicating pantoprazole and rabeprazole.
• Further adjustments for immunosuppressive drugs and renal events identified pantoprazole as the sole potential signal, with complete signal loss across age groups after antibacterial drug adjustment.

Conclusions:

• The observed association between PPIs and CDI is likely mediated by concurrent use of antibacterial drugs.
• Direct causation of CDI by PPIs is questionable, with co-medications playing a significant role.
• Pharmacovigilance data, when adjusted for confounding factors like antibacterial use, suggests PPIs are not a primary cause of CDI.