Prediction of Clostridium Difficile Infection Recurrence and Risk-Based Heterogeneity of Treatment Effect of Vnacomycin vs Fidaxomicin.

摘要

Despite successful therapy for Clostridium Difficile Infection (CDI), a significant number of patients will experience a recurrence. We aimed to develop a predictive model for recurrent CDI and to compare the efficacy of fidaxomicin and vancomycin in different risk groups. We included patients enrolled in two phase 3 clinical trials, comparing the efficacy and safety of fidaxomicin vs vancomycin in the treatment of CDI. Using logistic regression, we developed a predictive model for CDI recurrence, including significant predictors as well as established risk factors for recurrence. Patients were divided into tertiles based on their predicted probability of CDI recurrence. We compared the efficacy of fidaxomicin versus vancomycin within each risk tertile. The total number of patients was 794 patients. 150 patients (19%) experienced CDI recurrence by day 28. The following variables were included in the model for CDI recurrence: age>40 years (OR 1.27; p= 0.47), low creatinine clearance (OR 0.99; p= 0.06), low serum albumin (OR 0.89; p= 0.46), urinary tract infection (UTI) within one month prior to CDI (OR 1.61; p= 0.05), CDI in the past 3 months (OR 1.73; p= 0.02) and history of cardiovascular disease (OR 1.68; p= 0.02). Use of acid lowering agents was protective for CDI recurrence (OR 0.60; p= 0.01). Calibration and discrimination of the model were good (c-statistic=0.66 and a non-significant p-value for the Hosmer-Lemeshow test). While there was no risk-by-treatment interaction on the odds ratio scale, there was substantial variation in the absolute risk reduction across risk groups (absolute risk reduction was 17.1%, 14.6% and 2.1% in the high, intermediate and low risk groups respectively). CDI recurrence can be predicted on the basis of easily obtainable clinical factors at the time of initial presentation. Targeting fidaxomicin therapy to patients at higher risk of recurrence may be a worthwhile clinical strategy.