Fidaxomicin vs Vancomycin for the Treatment of a First Episode of Clostridium Difficile Infection: A Meta-analysis and Systematic Review

Abstract

Clostridium difficile infection (CDI) continues to possess a significant disease burden in the United States (US) as well as all over the world. Given the increase in severity and recurrence rate, the decrease in cure rate, and the fact that the virulent ribotype 027 strain remains one of the most commonly identified strains in the US, the Infectious Diseases Society of America (IDSA) published a clinical practice guideline in February 2018 moving away from metronidazole as the first-line treatment for initial CDI and recommending either oral vancomycin or fidaxomicin. The aim of this study is to evaluate the clinical data available comparing the efficacy of primary treatment of CDI between those two antibiotics. We performed a PubMed, PubMed Central, and ScienceDirect database search without restriction to regions, publication types, or languages. A comprehensive literature search was performed from January 1, 1980 up to March 20, 2018. We used the following keywords in different combinations: Clostridium difficile, Clostridium difficile infection, CDI, C. diff, C. difficile, fidaxomicin, vancomycin, pseudomembranous colitis, and antibiotic-associated colitis. The search was limited to human studies. Data were independently extracted by two reviewers with disagreements resolved by a third author. We pooled an odds ratio (OR) on two primary outcomes: Clinical cure rate and rate of recurrence during the follow-up period. The computer search was also supplemented with manual searches by the authors of the retrieved review articles and primary studies. The search phrase “((Clostridium difficile) AND vancomycin) AND fidaxomicin” had the highest yield results. We identified four observational studies with a total of 2,303 patients with CDI that met our inclusion criteria. Compared with vancomycin, fidaxomicin use was associated with a significantly lower recurrence of CDI with a pooled OR of 0.47 (95% confidence interval (CI), 0.37 - 0.60, I2 = 0). On the other hand, there was no significant association of fidaxomicin use with CDI cure rate compared to vancomycin with a pooled OR of 1.22 (95% CI, 0.93 - 1.60, I2 = 0). In light of the recently updated clinical practice guidelines by the IDSA, our review suggests that fidaxomicin has a more sustained clinical response with a statistically significant lower recurrence rate. Although fidaxomicin appears to be the better drug with statistical significance, its cost-effectiveness continues to be an ongoing controversy. More randomized clinical trials are needed to shed light on this matter to assess if there is any clinical significance in fidaxomicin superiority.

Drivers of Clostridioides difficile hypervirulent ribotype 027 spore germination, vegetative cell growth and toxin production in vitro

“…Current treatment for CDI has changed from metronidazole and vancomycin to fidaxomycin and vancomycin (14)(15)(16). Fidaxomycin carries a lower risk of recurrence, but its costeffectiveness is a topic of debate (17). The main risk factor to CDI is gut microbiota dysbiosis (12,18), associated with age and/or administration of broad-spectrum antibiotics.…”

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

“…Several studies have demonstrated a lower incidence of CDI recurrence in fidaxomicin‐treated patients compared with those receiving vancomycin, but these studies have been mostly limited to patients with an initial episode or first recurrence 3‐10 . Furthermore, there is a paucity of data in patients with multiple prior episodes of CDI.…”

Fecal Microbial Transplantation in Critically Ill Patients—Structured Review and Perspectives

“…Fidaxomicin, in addition to being active against vegetative forms, inhibits sporulation as well and has a narrower spectrum, thus less affecting the gut microbiota. Both of these factors translate to lower recurrence rate [2,39,40], but due to high cost, fidaxomicin remains the second line of treatment in most ICUs. In patients with fulminant colitis and/or septic shock refractory to conservative treatment, colectomy is recommended [37].…”