Path of least recurrence: A systematic review and meta‐analysis of fidaxomicin versus vancomycin for Clostridioides difficile infection

Abstract

Study Objective Current Clostridioides difficile infection (CDI) treatment guidelines recommend either fidaxomicin or vancomycin as first‐line therapy for initial and recurrent CDI. The objective of this study was to compare recurrence rates of fidaxomicin and vancomycin for the treatment of CDI in clinically relevant and real‐world subgroups via systematic review and meta‐analysis. Design & Data Sources A systematic literature review was performed by searching PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and http://clinicaltrials.gov from inception to September 1, 2021, for randomized and observational studies comparing vancomycin and fidaxomicin for CDI treatment in adults. The meta‐analysis was performed with Review Manager 5.4 software (Cochrane Library, Oxford, United Kingdom) using a random‐effects model. The primary end point was CDI recurrence after treatment with fidaxomicin or vancomycin. Subgroup analyses were conducted. Patients, Intervention, Measurements & Main Results The literature search identified six randomized controlled trials and eight observational trials, with a total of 3944 patients (fidaxomicin 32%; vancomycin 68%) included in the meta‐analysis. The mean age of study patients ranged from 46 to 75 years. The CDI recurrence rate was 22.4% (fidaxomicin 16.1%, vancomycin 25.4%). Compared to vancomycin, treatment with fidaxomicin was associated with a 31% reduction in the risk of recurrence (risk ratio 0.69; 95% confidence interval: 0.52–0.91, I2 = 62%). This reduction in recurrence risk was also seen in subgroup analyses for patients with initial CDI, first recurrent CDI, non‐severe and severe CDI, and in both inpatient and outpatient settings. Conclusion Our systematic review and meta‐analysis found fidaxomicin was consistently associated with a lower risk of CDI recurrence than vancomycin. These results confirm CDI guideline recommendations and indicate that fidaxomicin may be preferred over vancomycin to minimize CDI recurrence across multiple clinical scenarios, although further studies are warranted.

A Comparison of Currently Available and Investigational Fecal Microbiota Transplant Products for Recurrent Clostridioides difficile Infection

“…Fidaxomicin has demonstrated a reduction in the rate of first recurrences when compared to vancomycin [11]. However, despite guideline recommendations, clinical evidence is lacking in terms of fidaxomicin's efficacy in subsequent recurrences [12]. Considering the lack of a well-defined prevention strategy for multiple rCDI, managing this disease remains a challenging clinical issue.…”