Dial Sandra, Delaney J A Chris, Schneider Verena, Suissa Samy
Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University Health Centre, and the Department of Epidemiology and Biostatistics, McGill University, Montréal, Que.
CMAJ. 2006 Sep 26;175(7):745-8. doi: 10.1503/cmaj.060284.
The association between the use of proton pump inhibitors and the risk of Clostridium difficile-associated disease (CDAD) is controversial. In this study we re-examined a previously reported association between the use of proton pump inhibitors and the development of community-acquired CDAD, this time using an alternative case definition of the disease.
We performed a case-control study of community-acquired CDAD using a United Kingdom clinical research database. Patients receiving oral vancomycin therapy were identified as having CDAD, the only indication for this drug. Each case subject was matched with up to 10 control subjects. Neither the cases nor the controls had been admitted to hospital in the year before the date of the vancomycin prescription (index date). Conditional logistic regression analysis was used to adjust for key covariates.
We identified 317 cases of community-acquired CDAD treated with oral vancomycin therapy and 3167 matched control subjects. Exposure to a proton pump inhibitor in the 90 days before the index date was associated with an increased risk of CDAD (odds ratio [OR] 3.5, 95% confidence interval [CI] 2.3-5.2). Antibiotic exposure in the 90 days before the index date was also a significant risk factor for community-acquired CDAD (OR 8.2, 95% CI 6.1- 11.0), even though 45% of the case subjects had not received a prescription for an antibiotic during that period. Certain comorbidities, in particular renal failure, inflammatory bowel disease and malignant disease, as well as prior methicillin-resistant Staphylococcus aureus infection, were also associated with an increased risk.
Proton pump inhibitor use was associated with an increased risk of community-acquired CDAD, when cases were defined by receipt of prescription for oral vancomycin therapy. Prior antibiotic exposure was also a significant risk factor, but a significant proportion of the patients with community-acquired CDAD had no such exposure.
质子泵抑制剂的使用与艰难梭菌相关性疾病（CDAD）风险之间的关联存在争议。在本研究中，我们重新审视了先前报道的质子泵抑制剂使用与社区获得性CDAD发生之间的关联，此次使用了该疾病的另一种病例定义。
我们利用英国临床研究数据库对社区获得性CDAD进行了病例对照研究。接受口服万古霉素治疗的患者被确定为患有CDAD，这是该药物的唯一适应证。每个病例对象最多与10名对照对象匹配。病例组和对照组在万古霉素处方日期（索引日期）前一年均未住院。采用条件逻辑回归分析对关键协变量进行校正。
我们确定了317例接受口服万古霉素治疗的社区获得性CDAD病例和3167名匹配的对照对象。索引日期前90天内暴露于质子泵抑制剂与CDAD风险增加相关（比值比[OR]3.5，95%置信区间[CI]2.3 - 5.2）。索引日期前90天内的抗生素暴露也是社区获得性CDAD的一个显著危险因素（OR 8.2，95%CI 6.1 - 11.0），尽管45%的病例对象在此期间未接受抗生素处方。某些合并症，特别是肾衰竭、炎症性肠病和恶性疾病，以及既往耐甲氧西林金黄色葡萄球菌感染，也与风险增加相关。
当病例通过接受口服万古霉素治疗处方来定义时，质子泵抑制剂的使用与社区获得性CDAD风险增加相关。既往抗生素暴露也是一个显著危险因素，但相当比例的社区获得性CDAD患者没有此类暴露。
