DDW: Antibiotics Improve Colitis Symptoms

WASHINGTON, May 24 -- A combination of antibiotics aimed at Fusobacterium varium offers ulcerative colitis patients improved symptoms, a Japanese researcher said here.

The finding, from a double-blind, placebo-controlled trial, supports the idea that bacteria may play a role in the pathogenesis of the condition, according to Toshifumi Ohkusa, M.D., of the department of gastroenterology of Juntendo University in Tokyo.

The proposed pathogen is a member of a genus of anerobic, Gram-negative filamentous bacteria, Dr. Ohkusa told researchers at Digestive Disease Week.

Dr. Ohkusa and colleagues have been suggesting for several years that the bacteria play a role in ulcerative colitis. Two years ago he reported a small trial that showed inhibiting the bacteria benefited patients with mild to severe colitis.

But that study was small and not double-blind, so he and colleagues enrolled 210 patients with active colitis and randomized them to placebo or to a combination of three antibiotics -- ampicillin, tetracycline (both at 500 mg three times a day), and metronidazole (at 250 mg three times a day.)

The treatment period was two weeks long, followed by a year of follow-up. Concomitant medications for colitis were maintained throughout the study, with the exception that steroids were tapered off if the patient went into remission, he said.

The primary endpoints were clinical response at three months on Lichitiger's symptom score, St. Mark's index, and Mayo score, and mucosal healing on Matt's grading score. A range of secondary endpoints was evaluated at 12 months, he said.

The analysis found:

• For placebo patients, the Lichitiger's symptom score fell by one at three months, compared to a drop of two for antibiotic patients, a difference that was significant at P=0.0007.
• For placebo patients, the St. Mark's index fell by one at three months, compared to a drop of two for antibiotic patients, a difference that was significant at P=0.0002.
• For placebo patients, the Mayo score fell by one at three months, compared to a drop of two for antibiotic patients, a difference that was significant at P=0.0001.
• For placebo patients, the Matt's grading score did not change at three months, compared to a drop of one for antibiotic patients, a difference that was significant at P=0.0013.

Also, Dr. Ohkusa said, scores of frequency of watery diarrhea, nocturnal diarrhea, fecal incontinence, and general well-being were significantly improved in the treatment group.

Adverse events were higher in the treatment group -- mainly nausea and fever -- but there were no serious adverse events, Dr. Ohkusa said.

He concluded that the two-week antibiotic treatment is both effective and safe.

The study was weakened because the researchers did not check to see if the presence of the F. varium in the stool changed after antibiotic treatment, according to Hillary Steinhart, M.D., head of gastroenterology at Toronto's University Health Network, who was co-chairman of the session.

Dr. Steinhart said he wasn't persuaded by the results that the bacteria play a pathogenic role in ulcerative colitis.

"It doesn't convince me," he said. Among other things, he said, the researchers "didn't really make any attempt to look at either the fusobacterium itself in stool or other microbes."

Other studies suggest that inhibiting other microbes has a similar effect, he said, so that "it may be a general effect on the microbiology of the gut."

Dr. Steinhart said the currently accepted theory is that the ulcerative colitis is caused -- not by a pathogen -- but by alterations in the normal flora interacting with the host immune response.

"So that's another possible hypothesis as to why that study seemed to show a benefit -- it wasn't treating the fusobacterium, it was altering some other bacteria," he said.