Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA.
Am J Gastroenterol. 2013 Nov;108(11):1794-801. doi: 10.1038/ajg.2013.333. Epub 2013 Sep 24.
Observational studies suggest that proton pump inhibitors (PPIs) are a risk factor for incident Clostridium difficile infection (CDI). Data also suggest an association between PPIs and recurrent CDI, although large-scale studies focusing solely on hospitalized patients are lacking. We therefore performed a retrospective cohort analysis of inpatients with incident CDI to assess receipt of PPIs as a risk factor for CDI recurrence in this population.
Using electronic medical records, we identified hospitalized adult patients between 1 December 2009 and 30 June 2012 with incident CDI, defined as a first positive stool test for C. difficile toxin B and who received appropriate treatment. Electronic records were parsed for clinical factors including receipt of PPIs, other acid suppression, non-CDI antibiotics, and comorbidities. The primary exposure was in-hospital PPIs given concurrently with C. difficile treatment. Recurrence was defined as a second positive stool test 15-90 days after the initial positive test. C. difficile recurrence rates in the PPI exposed and unexposed groups were compared with the log-rank test. Multivariable Cox proportional hazards modeling was performed to control for demographics, comorbidities, and other clinical factors.
We identified 894 inpatients with incident CDI. The cumulative incidence of CDI recurrence in the cohort was 23%. Receipt of PPIs concurrent with CDI treatment was not associated with C. difficile recurrence (hazard ratio (HR)=0.82; 95% confidence interval (CI)=0.58-1.16). Black race (HR=1.66, 95% CI=1.05-2.63), increased age (HR=1.02, 95% CI=1.01-1.03), and increased comorbidities (HR=1.09, 95% CI=1.04-1.14) were associated with CDI recurrence. In light of a higher 90-day mortality seen among those who received PPIs (log-rank P=0.02), we also analyzed the subset of patients who survived to 90 days of follow-up. Again, there was no association between PPIs and CDI recurrence (HR=0.87; 95% CI=0.60-1.28). Finally, there was no association between recurrent CDI and increased duration or dose of PPIs.
Among hospitalized adults with C. difficile, receipt of PPIs concurrent with C. difficile treatment was not associated with CDI recurrence. Black race, increased age, and increased comorbidities significantly predicted recurrence. Future studies should test interventions to prevent CDI recurrence among high-risk inpatients.
观察性研究表明质子泵抑制剂（PPIs）是艰难梭菌感染（CDI）的一个发病因素。数据还表明 PPI 与复发性 CDI 之间存在关联，尽管缺乏专门针对住院患者的大规模研究。因此，我们对患有 CDI 的住院患者进行了回顾性队列分析，以评估在该人群中 PPI 的使用是否是 CDI 复发的一个风险因素。
使用电子病历，我们确定了 2009 年 12 月 1 日至 2012 年 6 月 30 日期间患有 CDI 的住院成年患者，其定义为首次粪便检测出艰难梭菌毒素 B 阳性且接受了适当治疗。对电子记录进行解析，以获取包括接受 PPI、其他抑酸剂、非 CDI 抗生素和合并症在内的临床因素。主要暴露因素为在接受艰难梭菌治疗时同时使用 PPI。复发定义为初次阳性检测后 15-90 天的第二次阳性粪便检测。用对数秩检验比较 PPI 暴露组和未暴露组的 CDI 复发率。采用多变量 Cox 比例风险模型来控制人口统计学、合并症和其他临床因素。
我们确定了 894 例患有 CDI 的住院患者。该队列中 CDI 复发的累积发生率为 23%。在接受 CDI 治疗时同时使用 PPI 与艰难梭菌复发无关（风险比（HR）=0.82；95%置信区间（CI）=0.58-1.16）。黑人种族（HR=1.66，95%CI=1.05-2.63）、年龄增加（HR=1.02，95%CI=1.01-1.03）和合并症增加（HR=1.09，95%CI=1.04-1.14）与 CDI 复发相关。鉴于接受 PPI 治疗的患者中 90 天死亡率较高（对数秩检验 P=0.02），我们还分析了存活至 90 天随访的患者亚组。同样，PPI 与 CDI 复发之间没有关联（HR=0.87；95%CI=0.60-1.28）。最后，PPIs 的使用时间或剂量与复发性 CDI 之间没有关联。
在患有艰难梭菌的住院成人中，在接受艰难梭菌治疗时同时使用 PPI 与 CDI 复发无关。黑人种族、年龄增加和合并症增加显著预测了复发。未来的研究应该测试预防高危住院患者 CDI 复发的干预措施。
