Antibiotic offers long-term benefit for irritable bowel syndrome

December 2005

A study of antibiotic treatment of patients with irritable bowel syndrome (IBS) shows significant improvement in symptoms not only during the course of treatment but 10 weeks later as well, according to a presentation at the 70th American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course, held in Honolulu.

Mark Pimentel, MD, from Cedars-Sinai Medical Center in Los Angeles, noted that although the patient cohort was small (n=87), the study demonstrated significant benefit for these patients.

The notion that IBS symptoms, including abdominal pain, bloating, diarrhea, or constipation, are caused by emotional stress and the commonplace determination of IBS therapy based on whether either diarrhea or constipation predominate have been supplanted in light of newer findings.

Pimentel and colleagues, seeing that bloating was the common symptom in all IBS cases, postulated that bacterial overgrowth in the small intestine subsequent to a lack of cleaning waves was the root cause. That understanding, Pimentel said in a Salix-sponsored teleconference from the ACG meeting, was confirmed by his own research and that of others showing neomycin, a nonabsorbed antibiotic, to be beneficial in IBS as compared with placebo.

“The trouble with neomycin was that despite dramatic improvements in symptoms, it couldn’t be used again because of enormous rates of bacterial resistance with a second use,” Pimentel said.

He noted further that with neomycin’s 5% absorption rate, undesirable inner ear, nerve and renal toxicities occurred. A search for a completely nonabsorbed antibiotic pointed to a European study that showed that a single course of rifaximin (Xifaxan, Salix Pharmaceuticals) successfully treated 70% of bacterial overgrowth in patients. Researchers proposed the current study subsequent to that finding.

Study methods

Pimentel and colleagues randomized patients at two centers to 1,200-mg rifaximin or placebo for 10 days. Participants completed a symptom questionnaire and took a lactulose breath test for seven days prior to and seven days following therapy. Researchers included IBS patients regardless of baseline lactulose breath test (methane positive or negative) or whether their predominant IBS complaint was diarrhea, constipation or their alternation.

Analysis revealed a significant benefit for the rifaximin patients as compared with placebo-treated patients. In an intention-to-treat analysis, researchers reported global improvement in 37.7% of the rifaximin group and 23.4% of the placebo group (P<.05). They noted a greater than 50% global improvement in 37% of rifaximin patients and in 16% of placebo patients (P<.05). Among subgroups, global improvement for rifaximin was found in 49% of those enrolled with diarrhea vs. 23% in placebo. For the smaller group of patients enrolling with constipation, the rifaximin benefit was numeric but not significant. Pimentel attributed the lack of significance to the small numbers in this group.

Pimentel underscored that in this investigation, when patient improvement was tracked for 10 additional weeks following completion of treatment, benefits persisted for most endpoints. In trials of agents used specifically against diarrhea or constipation, patients rebounded to pretrial bowel habits as soon as the drug was stopped, Pimentel stated.

“This means that we are really treating or effecting a change in their bowel function that is permanent or semi-permanent. This was a remarkable finding,” Pimentel said.

Another revelation emerging from the study, Pimentel said, was that breath test results predicted patients’ symptoms. Researchers measuring both methane and hydrogen found not only that the presence of methane correlated completely with constipation as the predominant symptom, but that the amount of methane correlated directly with the severity of constipation (Bristol Stool Scale Scores).

“This is a dramatic finding because it begins to unify IBS under one umbrella concept of bacterial overgrowth with the constituent bacteria dictating clinical outcome in these patients,” he said.

Pimentel concluded by commenting that in treating about 900 patients with IBS with rifaximin in the last year in his practice (among four physicians), he has seen more dramatic improvements than with any other agent.

For more information:

• Pimentel M. A non-absorbable antibiotic improves the symptoms of irritable bowel syndrome: a double-blind randomized controlled study. Abstract #42. Presented at the 70th American College of Gastroenterology (ACG) Annual Scientific Meeting and Postgraduate Course. Oct. 28-Nov. 2, 2005. Honolulu.
• DiStefano Michele, Coraza GR. Treatment of small intestine bacterial overgrowth and related symptoms by rifaximin. Chemotherapy. 2005;51:103-109.