Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials.

Abstract

BACKGROUND:

Clostridium difficile infection (CDI) is a common complication of antibiotic therapy that is 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 nonantibiotic, toxin-binding polymer, with vancomycin and metronidazole.

METHODS:

Patients with CDI were randomly assigned in a 2:1:1 ratio 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. The primary endpoint was clinical success, defined as resolution of diarrhea and absence of severe abdominal discomfort for more than 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 < .001), and metronidazole was inferior to vancomycin (P = .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 = .059). A post-hoc multivariate analysis that excluded tolevamer found 3 factors that were strongly associated with clinical success: vancomycin treatment, treatment-naive status, and mild or moderate CDI severity. Adverse events were similar among the treatment groups.

CONCLUSIONS:

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

• Authors: Stuart Johnson, Thomas J Louie, Dale N Gerding, Oliver A Cornely, Scott Chasan-Taber, David Fitts, Steven P Gelone, Colin Broom, David M Davidson, Polymer Alternative for CDI Treatment (PACT) investigators
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 59 Issue 3 Pg. 345-54 (Aug 01 2014) ISSN: 1537-6591 [Electronic] United States
• PMID: 24799326 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chemical References

• Anti-Bacterial Agents
• Polymers
• Sulfonic Acids
• Metronidazole
• Vancomycin
• styrenesulfonic acid polymer

Topics

• Adult
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (therapeutic use)
• Clostridioides difficile (drug effects)
• Clostridium Infections (drug therapy)
• Diarrhea (complications)
• Female
• Humans
• Male
• Metronidazole (therapeutic use)
• Middle Aged
• Polymers (therapeutic use)
• Recurrence
• Sulfonic Acids (therapeutic use)
• Vancomycin (therapeutic use)
• Young Adult