Barbulescu Andrei, Oskarsson Viktor, Lindblad Mats, Ljung Rickard, Brooke Hannah L
Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden,
Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Epidemiol. 2018 Oct 25;10:1573-1581. doi: 10.2147/CLEP.S159702. eCollection 2018.
Oral metronidazole used in combined regimens for eradication has been associated with an increased risk of acute pancreatitis; however, it is less clear whether a similar association exists for single-regimen metronidazole. We, therefore, examined the association of single and combined regimens of oral metronidazole with risk of acute pancreatitis.
In this population-based case-control study, all individuals in Sweden (aged 40-84 years) hospitalized with acute pancreatitis between January 2006 and December 2008 were identified from a national hospital register (n=5,996). Controls, matched for calendar year, age, and sex, were randomly sampled from a national population register (n=60,681). Data on oral metronidazole and covariates were extracted from national health and prescription registers. Odds ratios (ORs) of acute pancreatitis, according to timing of the latest metronidazole prescription before hospitalization, were estimated using logistic regression models. Confounding by indication was examined by contrasting the main results with the association when amoxicillin was used as exposure. The robustness of results was examined by calculating incidence rate ratios using a self-controlled case series approach.
After adjustment for potential confounders, there was a substantially increased risk of acute pancreatitis within 30 days of oral metronidazole exposure, both for single (OR: 4.06; 95% confidence interval [CI]: 1.90-8.64) and combined (OR: 11.80; 95% CI: 6.86-20.28) regimens, compared to nonexposure. In contrast, the adjusted OR was 1.79 (95% CI: 1.25-2.54) for current use of amoxicillin compared to nonexposure. These results were supported by the self-controlled cases series analysis (incidence rate ratio: 3.30; 95% CI: 2.69-4.06, for single and combined regimens of oral metronidazole pooled). There was no strong association between oral metronidazole and acute pancreatitis more than 30 days after exposure.
There was an increased risk of acute pancreatitis within 30 days of exposure to single and combined regimens of oral metronidazole. While reverse causality and confounding by indication cannot be entirely excluded, they are unlikely to fully explain the association. These results warrant an increased awareness among physicians.
在根除幽门螺杆菌的联合治疗方案中使用口服甲硝唑与急性胰腺炎风险增加有关；然而，单药治疗方案的甲硝唑是否存在类似关联尚不清楚。因此，我们研究了口服甲硝唑单药及联合治疗方案与急性胰腺炎风险之间的关联。
在这项基于人群的病例对照研究中，从国家医院登记册中识别出2006年1月至2008年12月期间在瑞典住院治疗急性胰腺炎的所有40-84岁个体（n=5996）。从国家人口登记册中随机抽取与病例在年份、年龄和性别上匹配的对照（n=60681）。从国家健康和处方登记册中提取口服甲硝唑及协变量的数据。根据住院前最后一次甲硝唑处方的时间，使用逻辑回归模型估计急性胰腺炎的比值比（OR）。通过将主要结果与以阿莫西林作为暴露因素时的关联进行对比，来检验指示性混杂。使用自控病例系列方法计算发病率比，以检验结果的稳健性。
在对潜在混杂因素进行调整后，与未暴露相比，口服甲硝唑暴露后30天内，单药治疗方案（OR：4.06；95%置信区间[CI]：1.90-8.64）和联合治疗方案（OR：11.80；95%CI：6.86-20.28）发生急性胰腺炎的风险均大幅增加。相比之下，与未暴露相比，当前使用阿莫西林的调整后OR为1.79（95%CI：1.25-2.54）。这些结果得到了自控病例系列分析的支持（口服甲硝唑单药及联合治疗方案合并后的发病率比：3.30；95%CI：2.69-4.06）。暴露后30天以上，口服甲硝唑与急性胰腺炎之间没有强关联。
口服甲硝唑单药及联合治疗方案暴露后30天内，急性胰腺炎风险增加。虽然不能完全排除反向因果关系和指示性混杂，但它们不太可能完全解释这种关联。这些结果值得医生提高认识。
