Prolonged Acid-Suppressive Therapy and Bacterial Infections: Balancing Risks and Benefits

Although proton pump inhibitors (PPIs) and histamine 2 receptor antagonists are widely prescribed for gastrointestinal disorders caused by excess stomach acid, chronic use has been associated with an increased risk of certain bacterial infections. This article reviews the evidence linking long-term use of these agents—particularly PPIs—to Clostridioides difficile, Salmonella, Campylobacter, spontaneous bacterial peritonitis in cirrhotic patients, community-acquired pneumonia, multidrug-resistant organisms, small intestinal bacterial overgrowth, and infections in young children. The authors advocate for pragmatic prescribing driven by benefit-risk trade-offs. When initiating acid-suppressive therapy, clinicians should carefully evaluate individual patient risk factors—including extremes of age, critical illness requiring hospitalization, and comorbidities such as cirrhosis and chronic kidney disease—and avoid prolonged use when not clinically warranted. Because acid-suppressive agents are widely available without a prescription, pharmacist-led counseling and deprescribing guidance are essential components of safe, individualized management.