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PROTON PUMP INHIBITORS (PPIs) INCREASE THE RISK OF SEVERE RESPIRATORY INFECTIONS, BUT DO NOT AFFECT THE RATES OF SEVERE INFECTIONS OF THE URINARY OR ALIMENTARY TRACT
LE Targownik, CJ Metge, S Leung
INTRODUCTION: The gastrointestinal tract is a potential reservoir for pathogenic organisms which may proceed to infect the gastrointestinal tract (enteritis, diverticulitis, or intra-abdominal infections, as well as organ systems outside the gastrointestinal tract, By decreasing intragastric acidity, proton pump inhibitors diminish the efficacy of one of the body’s defense mechanisms against infection, and may allow augment the ability of the gut to act as a source for these pathogens.
METHODS: We used the Manitoba Health databases to identify all subjects with acute admission to hospital with a primary diagnosis consistent with an infection with associated signs of system failure (i.e respiratory failure, acute renal failure, systemic sepsis). Cases were also divided into system subsets (respiratory, urinary tract, gastrointestinal, and other). Cases were matched with up to 10 controls matched on age, sex, comorbidity score, and index date. PPI use was identified through the provincial drug records, defined as use on the index date or within 14 days of the admission date. Conditional logistic regression was performed to determine the relation between PPI use and overall infections and specific class of infection, adjusting for comorbid illness including GERD, use of other medications, previous admissions for infections, and comorbid diseases. The effects of the intensity and duration of PPI therapy were also analyzed.
RESULTS: 1,728 cases were identified with admission for severe infections (731 respiratory, 296 GI, 284 UTI, 417 miscellaneous), who were matched to 17820 controls. PPI use within 14 days of the index date was associated with a 1.26 times increased risk of admission for a severe community acquired infection (95% CI 1.04-1.52), after adjusting for multiple potential confounders. This increased risk was likely driven by an increased risk specifically of respiratory infections (aOR 1.41, 95% CI: 1.04-1.91). PPI use was not associated with an increased risk of community acquired UTIs (aOR 0.85: 95% CI: 0.53-1.36) or GI infections. (aOR 1.14, 95% CI: 0.70-1.96). Duration and intensity of PPI exposure was not associated with an in creased risk of overall or any specific severe community acquired infection.
CONCLUSION: PPI use is associated with an increased risk of community acquired infections, which is mostly driven by an increased risk of serious respiratory infections. Further work is required to fully delineate the relationship between PPI use and respiratory disease.