Ischemic Colitis Is a Risk Factor for Clostridium difficile Infection

Introduction: Clostridium difficile infection (CDI) is an anaerobic infection that can carry detrimental outcomes for patients and is a growing burden to the US healthcare system. Various theories have been proposed for the etiopathogenesis of CDI, including antibiotic use, dysbiosis, and acid suppression. The role of ischemia in CDI has not been explored. We hypothesize that tissue ischemia is a risk factor for the development of CDI. The study aimed to assess whether ischemia was a risk factor for CDI using ischemic colitis as a target population. Methods: We performed a case-control study using the National Inpatient Sample (NIS) database in 2013. The study group included all patients with ischemic colitis (ICD 9 Code: 557.0, 557.1, 557.9) and the control group included all patients with diverticulitis (ICD 9 Code: 562.11, 562.13). Univariable and multivariable analyses were performed to assess the risk factors associated with CDI (ICD 9 Code: 008.45). The case and control groups were compared using the chi-square test for analysis. Continuous variables were compared using t-tests and categorical variables were compared using Rao-Scott chi-square tests. In addition, multivariable logistic regression analysis was performed to assess the association between disease group and CDI while adjusting for confounders. Univariable analysis was performed to assess differences between subjects with ischemic colitis and those with diverticulitis; continuous variables were compared using t-tests and categorical variables were compared using Rao-Scott chi-square tests. All analyses were done using SAS (version 9.4, The SAS Institute, Cary, NC). Results: We analyzed more than 30 million hospitalizations in 2013, with 120,490 being Ischemic colitis-related admissions and 309,940 being diverticulitis-related admissions. The rate of CDI was more in the ischemic colitis group than in the diverticulitis group (odds ratio [OR] = 1.39; 95% confidence interval [CI] [1.03-1.88], p=0.03). After adjusting for all variables, multivariate analysis showed CDI was associated with ischemic colitis (OR = 2.06; 95% CI 1.59-2.65, p<0.001). Conclusion: CDI was shown to be more prevalent in ischemic colitis than in diverticulitis control in this population-based study. As C. difficile is an anaerobe, we hypothesize that tissue hypoxia is a risk factor for its development. Further studies are needed to validate our findings.