Fidaxomicin for the Treatment of Clostridioides difficile Infection in Adult Patients: An Update on Results from Randomized Controlled Trials

Abstract

In recently updated international guidelines, fidaxomicin is preferentially recommended as first-line treatment over vancomycin both for the first episode of CDI and for rCDI, based on the results of different randomized controlled trials (RCTs). Although noninferiority was the rule in phase-3 RCTs with regard to the primary endpoint of clinical cure, for shaping these recommendations, particular attention was devoted to the improved global cure and reduced risk of recurrent CDI (rCDI) observed with fidaxomicin compared to vancomycin in RCTs. Overall, while the major driver of choice should remain the global benefit for the patient, consideration of available resources should be necessarily weighed in the balance, since fidaxomicin still remains more costly than vancomycin. Against this background, precisely stratifying risk groups for rCDI will represent a crucial research trajectory of future real-life studies on the treatment of first CDI episodes. In the current narrative review, we discuss the updated evidence from RCTs on the efficacy of fidaxomicin for the treatment of either the first CDI episode or rCDI, which eventually supports its positioning within current treatment algorithms and guidelines.

A Comparison of the Efficacy of Treatment With Fidaxomicin Versus Vancomycin in Clostridioides difficile Infection

“…Another study [ 14 ] with a higher percentage of patients treated in the first episode replicated the results of the pivotal trials. Nevertheless, all these post-authorization studies [ 12 , 14 , 26 , 27 ] confirmed the outcomes in both clinical cure and recurrence rate that appeared in the RCT [ 9 , 10 ] varying from 82% to 92% cure [ 12 , 14 , 26 , 27 ], with recurrence rate from 15% to 28% [ 12 , 14 , 16 , 26 , 28 ], similar to our results (cure 84% and recurrence 33% in fidaxomicin group). In addition, Gentry et al reported higher failure rates in patients with severe CDI treated with fidaxomicin compared to vancomycin (9.39% vs. 1.41%), as well as higher combined outcome clinical failure or recurrence at 12 weeks (32% in fidaxomicin vs 25% in vancomycin) [ 16 ].…”

Clostridioides difficile infection: a changing treatment paradigm

“…In the IDSA/SHEA guideline updates, a significant consideration is introduced regarding the recommendation of fidaxomicin over a standard course of vancomycin for initial CDI treatment – specifically, the choice of fidaxomicin hinges on resource availability [ 7 ]. The considerable cost associated with fidaxomicin has indeed posed a barrier to its widespread adoption [ 5 , 11 ]. Consequently, the IDSA/SHEA guidelines deem vancomycin as an acceptable alternative to fidaxomicin for patients with an initial CDI [ 7 ].…”

“…Furthermore, the FDA advises caution in administering bezlotoxumab, emphasising that it should be considered only when the benefits outweigh the risks in patients with a history of congestive heart failure [ 7 ]. Additionally, there remains limited knowledge regarding the efficacy of fidaxomicin in combination with bezlotoxumab for preventing recurrent CDI [ 5 ].…”

Clostridioides difficile Infection in an Italian Tertiary Care University Hospital: A Retrospective Analysis

“…Indeed, the benefit has been demonstrated to be higher in most fragile patients [46,47]. Risk group stratification strategies are needed to identify patients who are most likely to benefit from fidaxomicin [48].…”