Antimicrobial Peptides Are Differentially Expressed in Clostridium difficile Infection

Abstract

rence. Methods: Adults with CDI symptoms and a positive toxin test received oral fidaxomicin or vancomycin for ten days as part of a phase 3 clinical trial. Recurrence was defined as the reappearance of diarrhea and a positive stool toxin test within 4 weeks following completion of therapy. Multivariate analysis was used to identify patient characteristics at either the beginning or completion of therapy that correlated with recurrence or time to recurrence. Results: Of 518 patients (253 treatedwith fidaxomicin and 265with vancomycin), 106 had a recurrence of CDI (20.5%). The distribution of recurrences over timewas consistent with two distinct periods: early (within the first 2 weeks after stopping initial therapy; 10.5 reoccurrences/1000 patient days) and late (2 to 4 weeks after stopping initial therapy; 5.0 reoccurrences/1000 patient days). The table summarizes patient characteristics associated with increased incidence of early or late recurrence. Treatment with fidaxomicin was associated with a lower rate of early recurrence (5.9 recurrences/1000 patient days) compared with vancomycin (15.1 recurrences/1000 patient days, p<0.001). There was no difference between treatments in the rate of recurrence during weeks 3 and 4 of follow-up. Conclusions: CDI treatment with fidaxomicin resulted in a lower rate of early recurrence (within 14 days of completing therapy) than vancomycin. This differential effect is likely due to a less deleterious effect of fidaxomicin on normal fecal microflora. Late recurrence is likely related to a new infection and is affected by patient-related factors, not initial treatment choices. Such factors may define a group at high risk of a new infection and could guide prevention measures and treatment choices.