Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results From Two Multinational, Randomized, Controlled Trials

Abstract

Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794.

Age-Stratified Treatment Response Rates in Hospitalized Patients with Clostridium difficile Infection Treated with Metronidazole

“…Metronidazole is commonly used for the treatment of CDI and is guideline recommended for an initial episode of mild-to-moderate CDI (3,11). Observational and clinical trials have observed a decreased clinical cure rate with patients treated with metronidazole; however, the reasons for this decreased response rate are unclear (4)(5)(6)8). In this study, continued use of antibiotics, severe CDI, and a high Horn's index were predictive of patients at higher risk for refractory CDI when given metronidazole.…”

“…Oral metronidazole is a treatment option for C. difficile infection (CDI) and is recommended in the guidelines for the treatment of mild-to-moderate disease (3). However, observational (4) and randomized controlled (5,6) studies have demonstrated high clinical failure rates in patients with CDI given metronidazole. Colonic concentrations of metronidazole are relatively low and not predictable, and this drug is not considered by many to be an optimal pharmacologic agent for CDI (7).…”

New and emerging therapies for Clostridium difficile infection

“…12 The most significant recent findings are from a pooled analysis of two phase III trials of tolevamer (a toxin binding polymer), which failed to demonstrate equivalence to standard treatment. 13 These data additionally showed that clinical success occurred significantly less often following metronidazole compared to vancomycin therapy (73% and 81%, respectively, p=0.02). 13 However, metronidazole continues as first-line CDI therapy in many countries due to low acquisition cost and the perceived risk of VRE with vancomycin.…”

“…13 These data additionally showed that clinical success occurred significantly less often following metronidazole compared to vancomycin therapy (73% and 81%, respectively, p=0.02). 13 However, metronidazole continues as first-line CDI therapy in many countries due to low acquisition cost and the perceived risk of VRE with vancomycin. [6][7] Oral vancomycin is often recommended for severe or complicated CDI.…”

There is a trend favoring vancomycin vs. metronidazole in treating severe C. difficile infection

“…Furthermore, this meta-analysis determined the most effective method of treatment for CDI stratified by disease severity 3 . The most comprehensive study of the meta-analysis was by Johnson, et al, titled "Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials," which used two randomized controlled trials to assess treatment efficacy by both primary and secondary outcomes with three different medications, including vancomycin and metronidazole 2 . The meta-analysis contained two other studies that compared the efficacy of metronidazole with vancomycin in patients with severe CDI.…”