University of Texas Health Science Center at Houston School of Public Health, Center for Infectious Diseases, Houston, USA.
Aliment Pharmacol Ther. 2011 Dec;34(11-12):1269-81. doi: 10.1111/j.1365-2036.2011.04874.x. Epub 2011 Oct 17.
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.
质子泵抑制剂（PPIs）的使用在全球范围内不断增加。胃酸的抑制会改变对肠道细菌病原体的易感性。目的：本系统评价旨在根据已发表的文献，检查 PPI 使用与特定病原体引起的肠道感染易感性之间的关系，并讨论 PPI 增强肠道感染发病机制的潜在机制。方法：检索了 PubMed、OVID Medline 数据库。搜索词包括质子泵抑制剂和机制、作用、胃酸、肠道感染、腹泻、艰难梭菌、沙门氏菌、志贺氏菌和弯曲杆菌。结果：使用 PPIs 会增加胃 pH 值，促进肠道菌群生长，增加细菌易位，并改变各种免疫调节和抗炎作用。肠道病原体对胃酸 pH 值的敏感性和耐酸水平存在差异。通过多种机制，PPIs 似乎会增加对以下细菌肠道病原体的易感性：沙门氏菌、空肠弯曲菌、侵袭性大肠埃希菌、艰难梭菌的营养细胞、霍乱弧菌和李斯特菌。我们描述了使用 PPI 导致沙门氏菌、弯曲杆菌和艰难梭菌感染易感性增加的现有证据，相应的调整相对风险范围分别为 4.2-8.3（两项研究）；3.5-11.7（四项研究）；和 1.2-5.0（27 项研究中的 17 项）。结论：PPI 使用引起的严重低胃酸会导致细菌定植和增加肠道细菌感染的易感性。接受抗生素治疗的住院患者和前往腹泻高发地区的旅行者应考虑其医生对慢性 PPI 使用的临床影响。
