Newly developed antibiotic combination therapy for ulcerative colitis: a double-blind placebo-controlled multicenter trial

Am J Gastroenterol. 2010 Aug;105(8):1820-9. doi: 10.1038/ajg.2010.84. Epub 2010 Mar 9.


Objectives: Fusobacterium varium may contribute to ulcerative colitis (UC). We conducted a double-blind placebo-controlled multicenter trial to determine whether antibiotic combination therapy induces and/or maintains remission of active UC.

Methods: Patients with chronic mild-to-severe relapsing UC were randomly assigned to oral amoxicillin 1500 mg/day, tetracycline 1500 mg/day, and metronidazole 750 mg/day, vs. placebo, for 2 weeks, and then followed up. The primary study end point was clinical response (Mayo score at 3 months after treatment completion) and secondary end points were clinical and endoscopic score improvements at 12 months. Anti-F. varium antibodies were measured by enzyme-linked immunosorbent assay.

Results: Treatment and placebo groups each had 105 subjects. At the primary end point, response rates were significantly greater with antibiotics than with placebo (44.8 vs. 22.8%, P=0.0011). Endoscopic scores significantly improved at 3 months (P=0.002 vs. placebo). Remission rates were 19.0% (antibiotics) vs. 15.8% (placebo) at 3 months (P=0.59). At the secondary end point, response rates were significantly greater with antibiotics than with placebo (49.5 vs. 21.8%, respectively, P<0.0001). Endoscopic scores were significantly improved at 12 months after antibiotic treatment (P=0.002 vs. placebo). Remission rates had improved to 26.7% with antibiotics vs. 14.9% for placebo, at 12 months (P=0.041). F. varium antibody titers decreased in responders but not in nonresponders, and more in the antibiotic than in the placebo group. More pretreatment steroid-dependent UC patients discontinued corticosteroids after treatment completion (6 months: 28.6 vs. 11.8%, respectively, P=0.046; 9 months: 34.7 vs. 13.7%, respectively, P=0.019; and 12 months: 34.7 vs. 13.7%, respectively, P=0.019). These effects were greater in the subanalysis of the active group (Mayo scores of 6-12) than in that of total cases (0-12). No serious drug-related toxicities occurred.

Conclusions: The 2-week triple antibiotic therapy produced improvement, remission, and steroid withdrawal in active UC more effectively than a placebo.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adrenal Cortex Hormones / therapeutic use
  • Adult
  • Amoxicillin / administration & dosage
  • Amoxicillin / therapeutic use*
  • Colitis, Ulcerative / drug therapy*
  • Colitis, Ulcerative / microbiology*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endoscopy, Gastrointestinal
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fusobacterium Infections / drug therapy*
  • Fusobacterium Infections / microbiology*
  • Humans
  • Male
  • Metronidazole / administration & dosage
  • Metronidazole / therapeutic use*
  • Placebos
  • Statistics, Nonparametric
  • Tetracycline / administration & dosage
  • Tetracycline / therapeutic use*
  • Treatment Outcome


  • Adrenal Cortex Hormones
  • Placebos
  • Metronidazole
  • Amoxicillin
  • Tetracycline