Effectiveness of antibiotic combination therapy in patients with active ulcerative colitis: a randomized, controlled pilot trial with long-term follow-up.
OBJECTIVE
It is proposed that Fusobacterium varium might be one of the elusive pathogenic factors in ulcerative colitis (UC). Our goal was to assess whether an antibiotic combination therapy against F. varium is effective for induction and maintenance of remission of UC.


METHODS
Twenty chronic, active UC patients with F. varium infection were enrolled consecutively and were randomly assigned to receive amoxicillin, tetracycline or metronidazole per os for 2 weeks (treatment group; n=10), or no antibiotics (control group; n=10). F. varium was sensitive to the antibiotics. Symptom assessment, endoscopic and histological evaluations were performed blind before enrollment at 3-5 months and 12-14 months after the treatment. Serum immunoglobulins to F. varium were measured using an enzyme-linked immunosorbent assay (ELISA). Immunohistochemical detection of F. varium in biopsy specimens was carried out using the avidin-biotin complex method.


RESULTS
The clinical activity, endoscopic and histological scores in the treatment group decreased significantly at 3-5 and 12-14 months after the end of treatment compared with those in the control group (p=0.001-0.036). The remission rate in the treatment group was higher than that in the control group (p=0.037). In addition, the titers of antibody to F. varium and the F. varium density in the mucosa decreased at both the short- and long-term follow-ups in the treatment group (p=0.0002-0.049). No serious drug-related toxicity was observed during the trial.


CONCLUSIONS
The 2-week antibiotic combination therapy against F. varium was effective and safe in patients with chronic, active ulcerative colitis in this long-term follow-up study.
Ohkusa
Toshifumi
T
Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. ohkusa@med.juntendo.ac.jp
Nomura
Tetsuya
T
Terai
Takeshi
T
Miwa
Hiroto
H
Kobayashi
Osamu
O
Hojo
Mariko
M
Takei
Yoshiyuki
Y
Ogihara
Tatsuo
T
Hirai
Shu
S
Okayasu
Isao
I
Sato
Nobuhiro
N
D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003093:Colitis, Ulcerative / Q000175:diagnosis / Q000188:drug therapy* / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005673:Fusobacterium / Q000187:drug effects* / Q000302:isolation & purification; D005674:Fusobacterium Infections / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008795:Metronidazole / Q000627:therapeutic use; D008875:Middle Aged; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013752:Tetracycline / Q000627:therapeutic use; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D008795:Metronidazole; D000658:Amoxicillin; D013752:Tetracycline