2. Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Background: Clostridioides difficile infection causes chronic and sometimes life-threatening diarrhea in patients as a consequence of antibiotics overuse. A promising experimental procedure for recurrent and/ or refractory C. difficile infection is fecal microbiota transplantation therapy. The aim of this study was to analyze medical records of patients infected with recurrent and/or refractory C. difficilethat were treated with fecal microbiota transplantation therapy to investigate the relationship between time to clinical resolution and explanatory variables.
Methods: The analyses were based on a retrospective review of patients’ data. Data of ninety-two patients between 24 and 95 years of age of which 43.6% were males were available for analyses. Three variables, age group, gender and hospitalization status, were included in the analyses. For time-to-event endpoints, the comparison between two groups was done with the Kaplan-Meier estimator. The nonparametric logrank test was used to compare the survival distributions between two age groups. The Cox proportional hazard model was used to analyze age, gender and hospitalization status as risk factors to clinical resolution. The most satisfactory model was selected based on the value of Akaike’s information criterion. The proportional hazard assumptions and the overall model fit were assessed based on graphical evidence, hypothesis testing and residual analyses.
Results: Overall, clinical resolution was achieved for 92% of the patients. In fact, 95.7% of them in the age group younger than 65 years and 83.1% in the age group 65 years and older achieved clinical resolution. We found that the hazard of fecal microbiota transplantation to C. difficilein patients younger than 65 is twice as high as in patients who were 65 and older. On average, the age group younger than 65 years received 1.3 fecal microbiota transplantations, while the older age group received 2.2 fecal microbiota transplantations. Results of analyses indicate that the used models were appropriate.
Conclusion: Delivery of fecal microbiota transplantation via a retention enema is an effective alternative therapy for recurrent and/or refractory C. difficile infection. Age is strongly associated with clinical resolution, with older patients requiring more fecal microbiota transplantations and more time to be clinically resolved. The Kaplan-Meier estimators and the Cox proportional hazard model are adequate models to analyze data of patients infected with recurrent and/or refractory C. difficile. Randomized control trials with more variables are needed to confirm our findings and more deeply investigate the impact of other risk factors on clinical resolution.
Keywords: Clostridioides difficile infection, fecal microbiota transplantation, log-rank test, Kaplan-Meier estimator, Cox proportional hazard model, residual analysis