Effectiveness of fidaxomicin versus oral vancomycin in the treatment of recurrent clostridioides difficile

Abstract

What is Known and Objective The 2017 IDSA/SHEA Clinical Practice Guidelines for Clostridioides difficile infection (CDI) recommend treating recurrent episodes with fidaxomicin or oral vancomycin, but there is little evidence to support one strategy over another, particularly beyond the first recurrence. The aim of this study was to compare clinical outcomes in patients with recurrent CDI treated with vancomycin vs. fidaxomicin. Methods This retrospective study evaluated inpatients with recurrent CDI treated with vancomycin or fidaxomicin between 1 January 2013 and 1 May 2019. The primary outcome was CDI recurrence. Secondary outcomes included re‐infection, treatment failure, infection‐related length of stay (IRLOS) and in‐hospital all‐cause mortality (IHACM). The Wilcoxon rank‐sum test, Pearson's chi‐square test or Fisher's exact test was utilized, as appropriate. A multivariable logistic regression (MLR) model was used to estimate the adjusted odds ratio and 95% confidence interval assessing recurrence while adjusting for confounding variables. A survival analysis was also conducted. Results 135 patients met the inclusion criteria (35 fidaxomicin vs. 100 vancomycin). There was no difference in CDI recurrence [7 (20%) fidaxomicin vs. 11 (11%) vancomycin, p = 0.18]; this persisted in the MLR model (OR: 0.85 [95% CI 0.27–2.7]) and survival analysis (p = 0.1954). Additionally, there was no difference in re‐infection rate (p = 0.73), treatment failure (p = 0.13), IRLOS (p = 0.19) or IHACM (p = 0.65). What is New and Conclusion This represents the first analysis of CDI recurrence that included patients with >2 prior episodes of CDI. The study found no difference in additional recurrences when patients were treated with oral vancomycin vs fidaxomicin for recurrent CDI. However, the current study is limited by the small sample size available for inclusion. Prospective randomized studies with larger sample sizes are needed to confirm this study's conclusions.

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

“…For the sensitivity analysis for 28 to 59-day follow-up, the removal of the Rinaldi study evaluating rCDI and mrCDI patients decreased heterogeneity from 58% to 34% without changing the overall RR; the removal of the Guery study decreased heterogeneity from 58% to 45% and yielded a non-significant RR. 9,28 The removal of both the Rinaldi and Guery study decreased heterogeneity to 0%, with a similar RR and tighter CI relative to the original analysis (see Figure A4). For the sensitivity analysis for 60 to 90 day follow-up, heterogeneity decreased to 0% with the exclusion of the Polivkova study resulting in a similar RR (see Figure A5).…”

“…Of the remaining 22 full-text articles reviewed, 14 studies (six RCTs and eight observational trials) met eligibility criteria for the final meta-analysis (Figure 1). [9][10][11][12][20][21][22][23][24][25][26][27][28][29][30] Reasons for excluding full-text articles included an unspecified follow-up period for recurrence, missing data, population overlap, and concomitant use of fecal microbiota transplantation. [31][32][33][34][35][36][37] For included RCTs, three studies were assessed to have a low risk of bias and three with some concerns, primarily due to problems related to the unblinding of standard-of-care treatments (Figure 2A).…”

“…The sensitivity analysis for removal of individual studies found over 10% reductions in heterogeneity with the removal of the Guery study (the only RCT evaluating fidaxomicin extended-pulsed dosing and the Polivkova study). 9,24 While these studies had the lowest Reports excluded: Adjunctive fecal microbiota transplantation (n=2) 32,33 Population overlap (n=1) 31 Missing data (n=3) 34,35,37 Unclear follow-up period (n=1) 36 Studies included in review (n=14) [9][10][11][12][21][22][23][24][25][26][27][28][29][30] Controlled trials (n=6) Observational trials (n=8)…”

Impact of Updated Clinical Practice Guidelines on Outpatient Treatment for Clostridioides difficile Infection and Associated Clinical Outcomes

“…Again, the absolute reduction in CDI recurrence was similar to the randomized trials. While it should be noted that some observational studies conducted in certain high-risk groups [ 18 , 19 ] have not found a meaningful difference in outcomes between fidaxomicin and vancomycin, several other observational studies conducted by Goldenberg et al [ 20 ], Gallagher et al [ 21 ], and Polivkova et al [ 22 ] have demonstrated fidaxomicin’s superiority over vancomycin in treating CDI. The evidence on the superiority of fidaxomicin over vancomycin has also been acknowledged in the latest update to IDSA guidelines for CDI treatment published in 2021 [ 11 ], which now recommends fidaxomicin as first-line treatment for both initial and recurrent CDI episodes, with vancomycin an acceptable alternative.…”

Treatment of Clostridioides difficile infection: from guidelines to clinical practice

“…From observational studies, both FDX and BZL show lower efficacy from the first and, definitely, the second recurrence [10][11][12]; hence, probably positioning these drugs in the second recurrence and thereafter, provides a sign of their lower efficiency. In the event of a second recurrence and particularly in the subsequent ones, the most effective treatment today is FMT.…”