Abstract & Overview
Side effects of PPIs 541 Risk of infections The association between the use of PPIs and the increased risk of enteric and extraintestinal infections, particularly Clostridium difficile (CDI) and pneumonia, has been investigated by several studies.Different underlying mechanisms have been identified, namely: 1) reduction of gastric acidity, which may allow organisms to reach the intestine more easily (gastric acid resistance); 2) antineutrophilic effect; and 3) changes induced in the intercellular tight junctions, which may favor bacterial translocation to other organs (intestinal permeability).Enteric infection Several meta -analyses reported a significant association between PPI use and CDI.3-5 Kwok et al 4 reported an increased risk of CDI in PPI users compared with nonusers with an odds ratio (OR) of 1.74 (95% CI, 1.47-2.85),which further increased if PPIs had been associated with antibiotic treatment (OR, 1.96; 95% CI, 1.03-3.7).Clostridium difficile spores are generally resistant to the gastric environment.However, Introduction Proton pump inhibitors (PPIs) are among the most commonly prescribed drugs as a consequence of the increasing incidence of gastroesophageal reflux disease (GERD) and acid--related disorders in the population. 1 However, PPIs are also prescribed in a large number of patients with inappropriate indications.Despite being a well -tolerated class of drugs with a good safety profile, a growing body of evidence has been published regarding potential side effects of PPIs, particularly related to their long--term use. 2 Indeed, prolonged treatment with PPIs has been associated with increased risk of infections, bone fractures, and renal damage, malabsorption of vitamins and minerals, and other complications (FIguRE 1), although with different levels of evidence and, in many cases, conflicting results.This review aims to analyze the most important and established side effects of long -term use of PPIs, together with practical considerations for their clinical management.