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Vancomycin, Metronidazole, or Tolevamer for Clostridium difficile Infection: Results from Two Multinational, Randomized, Controlled Trials.
Clin Infect Dis. 2014 May 5;
Authors: Johnson S, Louie TJ, Gerding DN, Cornely OA, Chasan-Taber S, Fitts D, Gelone SP, Broom C, Davidson DM
Abstract
Background. Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is also treated with antibiotics, contributing to ongoing disruption of the colonic microbiota and CDI recurrence. Two multinational trials were conducted to compare the efficacy of tolevamer, a non-antibiotic, toxin-binding polymer with vancomycin and metronidazole. Methods. Patients with CDI were randomly assigned to oral tolevamer 9 g (loading dose) followed by 3 g every 8 hours for 14 days, vancomycin 125 mg every 6 hours for 10 days, or metronidazole 375 mg every 6 hours for 10 days in a 2:1:1 ratio. The primary endpoint was clinical success defined as resolution of diarrhea and absence of severe abdominal discomfort for >2 consecutive days including day 10. Results. In a pooled analysis, 563 patients received tolevamer, 289 received metronidazole, and 266 received vancomycin. Clinical success of tolevamer was inferior to both metronidazole and vancomycin (P<0.001), and metronidazole was inferior to vancomycin (P=0.02) (44.2% [n=534], 72.7% [n=278], and 81.1% [n=259], respectively). Clinical success in patients with severe CDI who received metronidazole was 66.3% compared with vancomycin, which was 78.5%. (P=0.059). A post-hoc multivariate analysis that excluded tolevamer found three factors that were strongly associated with clinical success: vancomycin treatment, treatment-naïve status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups. Conclusion. Tolevamer was inferior to antibiotic treatment of CDI, and metronidazole was inferior to vancomycin. Trial Registration. clinicaltrials.gov NCT00106509 and NCT00196794.
PMID: 24799326 [PubMed - as supplied by publisher]