Problem: Gastroesophageal Reflux Disease and Peptic Ulcer Disease Long-term proton-pump inhibitor (PPI) use is associated with which health problem(s)? While conflicting data exist about the risk of chronic PPI, long-term side-effects can occur, including hypergastrinemia, fractures, infections (Clostridium difficile colitis and bacterial gastroenteritis), vitamin B12 deficiency, and hypomagnesemia. In the short term, PPIs may increase the risk of community-acquired pneumonia; however, this risk appears to disappear after long-term use.