Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection
Examination of Potential Mechanisms To Explain the Association between Proton Pump Inhibitors and Clostridium difficile Infection
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DOI：
10.1128/aac.00252-09
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发表时间：
2009-10-01
影响因子：
4.9
通讯作者：
Donskey, Curtis J.
中科院分区：
文献类型：
--
作者：
Nerandzic, Michelle M.;Pultz, Michael J.;Donskey, Curtis J.
在最近的几项研究中，质子泵抑制剂(PPI)与艰难梭菌感染(CDI)有关。然而，其他研究没有显示这种联系，PPI促进CDI的机制也没有阐明。我们推测了两种可能的致病机制：第一，通过提高pH值，PPI可能会阻止胃内容物杀死艰难梭菌孢子；第二，接受PPI治疗的患者的胃内容物可能会促进艰难梭菌孢子的萌发和生长。对6株艰难梭菌的孢子在酸性胃内容物中的存活率进行了测定。通过80℃热休克、相差显微镜和孵育24小时后乙醇休克，在患者的胃内容物以及小鼠的胃、小肠和盲肠内容物中检测孢子的萌发和生长。艰难梭菌孢子存活并在酸性pH的非胆汁性胃内容物中休眠。患者未经修饰的胃内容物中不会发生发芽，但添加牛磺胆酸和氨基酸后会发生发芽。在小鼠中，胃内容物中没有萌发，但小肠和盲肠内容物中发生了萌发。总之，艰难梭菌的孢子在酸性胃内容物中存活，没有在胃内容物中萌发和生长，这可能是由于缺乏必要的发芽物质，如牛磺胆酸。我们的结果表明，胃内PPI的作用与CDI的发病机制无关。
Proton pump inhibitors (PPIs) have been associated with Clostridium difficile infection (CDI) in several recent studies. However, other studies have not shown this association, and the mechanism by which PPIs might promote CDI has not been elucidated. We hypothesized two possible mechanisms of causation: first, by raising pH, PPIs may prevent gastric contents from killing C. difficile spores; second, gastric contents of PPI-treated patients may promote germination and outgrowth of C. difficile spores. Survival rates of spores from six different strains of C. difficile in acidic gastric contents were assessed using quantitative cultures on selective media. Germination and outgrowth of spores were assessed by heat shock at 80 degrees C, phase-contrast microscopy, and ethanol shock after incubation for 24 h in the gastric contents of patients and in the gastric, small intestinal, and cecal contents of mice. C. difficile spores survived and remained dormant in nonbilious gastric contents with acidic pH. Germination did not occur in unmodified gastric contents of patients but did occur with the addition of taurocholic acid and amino acids. In mice, germination did not occur in gastric contents but did occur in small intestinal and cecal contents. In summary, C. difficile spores survived in acidic gastric contents and did not undergo germination and outgrowth in gastric contents, probably due to lack of essential germinants, such as taurocholic acid. Our results suggest that the effects of PPIs in the stomach do not contribute to the pathogenesis of CDI.