title: 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.affiliation: Loyola University Medical Center and Hines Veterans Administration Hospital, Chicago, Illinois.
authors.forename: Stuart
authors.initials: S
authors.lastname: Johnson
authors.affiliation: University of Calgary, Alberta, Canada.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Louie
authors.affiliation: Loyola University Medical Center and Hines Veterans Administration Hospital, Chicago, Illinois.
authors.forename: Dale N
authors.initials: DN
authors.lastname: Gerding
authors.affiliation: Department of Internal Medicine, Clinical Trials Centre Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Germany.
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
authors.affiliation: Genzyme, Cambridge, Massachusetts.
authors.forename: Scott
authors.initials: S
authors.lastname: Chasan-Taber
authors.affiliation: ViroPharma Incorporated, Exton, Pennsylvania.
authors.forename: David
authors.initials: D
authors.lastname: Fitts
authors.affiliation: ViroPharma Incorporated, Exton, Pennsylvania.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Gelone
authors.affiliation: ViroPharma Incorporated, Exton, Pennsylvania.
authors.forename: Colin
authors.initials: C
authors.lastname: Broom
authors.affiliation: Genzyme, Cambridge, Massachusetts.
authors.forename: David M
authors.initials: DM
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects*; D003015:Clostridium Infections / Q000188:drug therapy*; D003967:Diarrhea / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use*; D008875:Middle Aged; D011108:Polymers / Q000627:therapeutic use*; D012008:Recurrence; D013451:Sulfonic Acids / Q000627:therapeutic use*; D014640:Vancomycin / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D011108:Polymers; D013451:Sulfonic Acids; D008795:Metronidazole; D014640:Vancomycin; C077114:styrenesulfonic acid polymer
keywords: Clostridium difficile; infection; metronidazole; vancomycin