The Use of PPIs and Susceptibility to Enteric Infection
The Use of PPIs and Susceptibility to Enteric Infection
Background The use of proton pump inhibitors (PPIs) is increasing worldwide. Suppression of gastric acid alters the susceptibility to enteric bacterial pathogens.
Aim This systematic review was undertaken to examine the relationship between PPI use and susceptibility to enteric infections by a specific pathogen based on published literature and to discuss the potential mechanisms of PPI enhanced pathogenesis of enteric infections.
Methods PubMed, OVID Medline Databases were searched. Search terms included proton pump inhibitors and mechanisms of, actions of, gastric acid, enteric infections, diarrhoea, Clostridium difficile, Salmonella, Shigella and Campylobacter.
Results The use of PPIs increases gastric pH, encourages growth of the gut microflora, increases bacterial translocation and alters various immunomodulatory and anti-inflammatory effects. Enteric pathogens show variable gastric acid pH susceptibility and acid tolerance levels. By multiple mechanisms, PPIs appear to increase susceptibility to the following bacterial enteropathogens: Salmonella, Campylobacter jejuni, invasive strains of Escherichia coli, vegetative cells of Clostridium difficile, Vibrio cholerae and Listeria. We describe the available evidence for enhanced susceptibility to enteric infection caused by Salmonella, Campylobacter and C. difficile by PPI use, with adjusted relative risk ranges of 4.2–8.3 (two studies); 3.5–11.7 (four studies); and 1.2–5.0 (17 of 27 studies) for the three respective organisms.
Conclusions Severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increased susceptibility to enteric bacterial infection. The clinical implication of chronic PPI use among hospitalized patients placed on antibiotics and travellers departing for areas with high incidence of diarrhoea should be considered by their physicians.
Proton pump inhibitors (PPIs) are the major treatment for many gastroesophageal diseases. Omeprazole (1988), lansoprazole (1995), pantoprazole (1997), rabeprazole (1999) and esomeprazole (2001) are the widely used PPIs clinically and omeprazole is available over-the-counter without a prescription in many countries. According to one report, PPIs are the third most prescribed medications in United States with 13.9 billion dollar sales per year. With the widespread use of PPIs worldwide, the authors of this review have attempted to put the added risk for acquisition of enteric infection in PPI-treated people into perspective based on the published literature.
Bacterial colonisation by exogenous enteric microbes is kept in check by a number of host defence mechanisms such as gastric acid, host gut microflora, local gut immunity, intestinal motility, intestinal secretion and epithelial barrier. These forces work synergistically in maintaining intestinal homeostasis. A compromise in host defences may influence susceptibility to various enteric pathogens. In this review we will discuss the association of PPI treatment and enhanced susceptibility to enteric infection with an emphasis on potential mechanisms.
Abstract and Introduction
Abstract
Background The use of proton pump inhibitors (PPIs) is increasing worldwide. Suppression of gastric acid alters the susceptibility to enteric bacterial pathogens.
Aim This systematic review was undertaken to examine the relationship between PPI use and susceptibility to enteric infections by a specific pathogen based on published literature and to discuss the potential mechanisms of PPI enhanced pathogenesis of enteric infections.
Methods PubMed, OVID Medline Databases were searched. Search terms included proton pump inhibitors and mechanisms of, actions of, gastric acid, enteric infections, diarrhoea, Clostridium difficile, Salmonella, Shigella and Campylobacter.
Results The use of PPIs increases gastric pH, encourages growth of the gut microflora, increases bacterial translocation and alters various immunomodulatory and anti-inflammatory effects. Enteric pathogens show variable gastric acid pH susceptibility and acid tolerance levels. By multiple mechanisms, PPIs appear to increase susceptibility to the following bacterial enteropathogens: Salmonella, Campylobacter jejuni, invasive strains of Escherichia coli, vegetative cells of Clostridium difficile, Vibrio cholerae and Listeria. We describe the available evidence for enhanced susceptibility to enteric infection caused by Salmonella, Campylobacter and C. difficile by PPI use, with adjusted relative risk ranges of 4.2–8.3 (two studies); 3.5–11.7 (four studies); and 1.2–5.0 (17 of 27 studies) for the three respective organisms.
Conclusions Severe hypochlorhydria generated by PPI use leads to bacterial colonisation and increased susceptibility to enteric bacterial infection. The clinical implication of chronic PPI use among hospitalized patients placed on antibiotics and travellers departing for areas with high incidence of diarrhoea should be considered by their physicians.
Introduction
Proton pump inhibitors (PPIs) are the major treatment for many gastroesophageal diseases. Omeprazole (1988), lansoprazole (1995), pantoprazole (1997), rabeprazole (1999) and esomeprazole (2001) are the widely used PPIs clinically and omeprazole is available over-the-counter without a prescription in many countries. According to one report, PPIs are the third most prescribed medications in United States with 13.9 billion dollar sales per year. With the widespread use of PPIs worldwide, the authors of this review have attempted to put the added risk for acquisition of enteric infection in PPI-treated people into perspective based on the published literature.
Bacterial colonisation by exogenous enteric microbes is kept in check by a number of host defence mechanisms such as gastric acid, host gut microflora, local gut immunity, intestinal motility, intestinal secretion and epithelial barrier. These forces work synergistically in maintaining intestinal homeostasis. A compromise in host defences may influence susceptibility to various enteric pathogens. In this review we will discuss the association of PPI treatment and enhanced susceptibility to enteric infection with an emphasis on potential mechanisms.
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