Oral fidaxomicin versus vancomycin for the treatment of Clostridioides difficile infection: A systematic review and meta-analysis of randomized controlled trials

Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea in healthcare systems [1,2] and was reported as an urgent threat by the Centers for Disease Control and Prevention in 2019 [3]. The use of broad-spectrum antibiotics, such as clindamycin, carbapenems, cephalosporins, and fluoroquinolones, is strongly associated with the onset of CDI due to the disruption of normal microbiota [[4], [5], [6], [7], [8]]. Clinical manifestations range from mild to moderate to severe complicated CDI, including pseudomembranous colitis or toxic megacolon [9]. One serious challenge in overcoming CDI is the high recurrence rates after standard treatment. Various factors, including older age (≥65 years), systemic antibiotics, serious underlying diseases, previous episodes, and proton pump inhibitors are associated with recurrence [[10], [11], [12], [13]]. As previous episodes of CDI are increasing, recurrence rates are also increasing. Actually, first recurrence rates are approximately 30% [[14], [15], [16], [17], [18], [19]] and second recurrence rates are about 30–65% [[19], [20], [21]]. These troublesome characteristics lead to long hospital stays, increased treatment costs, and higher mortality [19,22].

Vancomycin (VCM) and metronidazole (MNZ) are the mainstay of treatment for CDI in Japan. VCM is significantly more effective than MNZ in severe cases; on the other hand, VCM is associated with no significantly higher clinical cure rates compared with MNZ in non-severe cases. In addition, recurrence rates were not significantly different between them [23,24]. Therefore, considering the possibility of emergence of VCM-resistant Enterococci [25,26] and the low treatment cost of MNZ [27], VCM is recommended for severe cases and MNZ is recommended for non-severe cases by some guidelines [[28], [29], [30]]. Recently, fidaxomicin (FDX), a narrow-spectrum and macrocyclic antibiotic, has received considerable attention as a novel alternative therapeutic agent to VCM and MNZ. This is because FDX contributes to significantly higher global cure rates and significantly lower recurrence rates than VCM, based on several randomized controlled trials (RCTs) [31,32]. These results have advanced FDX as the first-choice therapy in Europe and America [26,29]. However, compared with VCM, the superiority of FDX and the efficacy profile for certain patient groups (non-severe cases, severe cases, initial CDI cases, recurrent CDI cases, strain type, etc.) have not been sufficiently evaluated by a systematic review and meta-analysis.

Therefore, we performed a systematic review and meta-analysis to evaluate the global cure rates, clinical cure rates, and recurrence rates for efficacy and adverse event rates for safety between FDX and VCM. The present study had two major objectives: (i) to elucidate whether FDX is superior to VCM and (ii) to clarify the efficacy profile of FDX.

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