Rifaximin for IBS

[Glynis Steele]

http://www.nejm.org/doi/full/10.1056/NEJMoa1004409

Background
Evidence suggests that gut flora may play an important role in the pathophysiology of the irritable bowel syndrome (IBS). We evaluated rifaximin, a minimally absorbed antibiotic, as treatment for IBS.

Full Text of Background...

Methods
In two identically designed, phase 3, double-blind, placebo-controlled trials (TARGET 1 and TARGET 2), patients who had IBS without constipation were randomly assigned to either rifaximin at a dose of 550 mg or placebo, three times daily for 2 weeks, and were followed for an additional 10 weeks. The primary end point, the proportion of patients who had adequate relief of global IBS symptoms, and the key secondary end point, the proportion of patients who had adequate relief of IBS-related bloating, were assessed weekly. Adequate relief was defined as self-reported relief of symptoms for at least 2 of the first 4 weeks after treatment. Other secondary end points included the percentage of patients who had a response to treatment as assessed by daily self-ratings of global IBS symptoms and individual symptoms of bloating, abdominal pain, and stool consistency during the 4 weeks after treatment and during the entire 3 months of the study.

Full Text of Methods...

Results
Significantly more patients in the rifaximin group than in the placebo group had adequate relief of global IBS symptoms during the first 4 weeks after treatment (40.8% vs. 31.2%, P=0.01, in TARGET 1; 40.6% vs. 32.2%, P=0.03, in TARGET 2; 40.7% vs. 31.7%, P<0.001, in the two studies combined). Similarly, more patients in the rifaximin group than in the placebo group had adequate relief of bloating (39.5% vs. 28.7%, P=0.005, in TARGET 1; 41.0% vs. 31.9%, P=0.02, in TARGET 2; 40.2% vs. 30.3%, P<0.001, in the two studies combined). In addition, significantly more patients in the rifaximin group had a response to treatment as assessed by daily ratings of IBS symptoms, bloating, abdominal pain, and stool consistency. The incidence of adverse events was similar in the two groups.

Glynis

 

[CBS]

IMO, a lot of IBS is actually small intestinal bacterial overgrowth (SIBO) that has been misdiagnosed.

Because no reliable biologic or structural markers have been identified, the effects of pharmacotherapy are typically assessed by asking patients to report whether they had adequate relief of IBS symptoms.

Duodenal aspirate tested for anaerobic bacteria or a hydrogen breath test could have been done to distinguish IBS from SIBO.

The data on the efficacy of Rifaxamin in SIBO is fairly extensive. Still, this article is good news. A lot of people have been dealing with symptoms for years and they may now start getting the treatment they need. The biggest obstacle here is going to be cost (and push back from insurance companies). Rifaxamin is expensive ($12 a tablet three times a day for fourteen days = $500) and the treatment typically has to be repeated once every 3-5 months. Rifaxamin is a powerful antibiotic. The up side is that it does not cross out of the intestinal track into the rest of the body. The big question is - what are the long term effects of taking an extended course of this medication (it is typically prescribed for traveler's diarrhea at a dose of three tablets a day for three days - 9 tablets for a one time use versus the recommended 54 tablets) several times a year?

All of that said, it appears to be an excellent article on the real benefits of Rifaxamin for many people with GI issues. My own experience has been that the bloating is a key symptom that suggests a person my benefit from Rifaxamin Tx (especially if the bloating is temporarily relieved by Gas-x - generic name: simethecone).

 

[drex13]

I could not take Rifaximin. After the third day, I had horrible diahrrea, cramping, and nausea and had to stop taking it on the 5th day. It was not a good experience and I have not fully recovered from it. That was back in July of 2010. There seems to be a fair amount of evidence backing up it's use, but it was not good for me.

 

[ballard]

I took two tablets of Rifaximin (400mg) twice a day for 10 days. It worked well for I.B.S for about 3 months. My insurance would only pay for
one trial of the drug. I would use it again if my insurance would cover it. I don't recall any side effects.

 

[ixchelkali]

A question based on complete ignorance about Rifaximin: since it's an antibiotic, doesn't it kill the good flora as well as the bad? I put some effort into cultivating healthy intestinal flora, because I find that really helps keep my IBS controlled. I hate having to take antibiotics because that means starting back at square one in growing my good-guy gut biota.

My belief, not necessarily based on science (call it a GUT feeling) is that IBS, as well as some other diseases, occurs when the good-guy gut bacteria get outnumbered by the pathogenic flora, such as clostridium, e. coli, and staph. I try to prevent that by cultivating healthy probiotics, limiting sugar, getting plenty of different kinds of fiber. I look on it as farming, and consider a bout of diarrhea or taking antibiotics as a crop failure. So my knee-jerk reaction to taking antibiotics for IBS is negative. Am I missing something here?

 

[CBS]

A question based on complete ignorance about Rifaximin: since it's an antibiotic, doesn't it kill the good flora as well as the bad? I put some effort into cultivating healthy intestinal flora, because I find that really helps keep my IBS controlled. I hate having to take antibiotics because that means starting back at square one in growing my good-guy gut biota.

My belief, not necessarily based on science (call it a GUT feeling) is that IBS, as well as some other diseases, occurs when the good-guy gut bacteria get outnumbered by the pathogenic flora, such as clostridium, e. coli, and staph. I try to prevent that by cultivating healthy probiotics, limiting sugar, getting plenty of different kinds of fiber. I look on it as farming, and consider a bout of diarrhea or taking antibiotics as a crop failure. So my knee-jerk reaction to taking antibiotics for IBS is negative. Am I missing something here?

Hi Ixchelkali,

Excellent point. Rifaxamin is not kind to the good guys living in your gut. Taking this antibiotic for an extended course will decimate the friendly biota. My GI prescribes probiotics to help repopulate the crop. Not a panacea but it helps.

In some cases, the story is a bit more complex than just diet and good husbandry. Diet Immune dysfunction and lack of motility can cause over growth. Diabetic neuropathy is a classic cause of dysmotilty. My GI feels that both immune suppression and neurally mediated dysmotilty are factors in my SIBO. I also think that reduced activity is an issue. The simple mechanics of moving your body improves motility.

That said, your points about IBS being caused by the bad guys out numbering the good guys is spot on. Limiting sugar and lots of good fiber is key. Motility can be helped with several small meals, eating slowly and thoroughly chewing your food. All of this is important in limiting the need to use an extreme measure like Rifaximin. Anti-virals are also part of trying to minimize the neural dysfunction/potential damage.

 

[Glynis Steele]

I think it depends what has overgrown in your bowel. Even the good bacteria can overgrow, creating an acidic envoironment, which takes out other bacteria, and can change the bowel pH. Some people here cannot take acidophilus, react to it, become more ill and develop worsening symptoms. Each person's gut bacteria is different, and I think it would be helpful to tailor treatment based on this, instead of going in with an antibiotic which might not be appropriate. If probiotics are helpful, brilliant, but not all do well on them.

Glynis

 

[guest]

Same story on science daily. I guess it's worth a try.

http://www.sciencedaily.com/releases/2011/01/110105194836.htm

ScienceDaily (Jan. 6, 2011) — A ground-breaking antibiotic therapy developed at Cedars-Sinai Medical Center is the first potential drug treatment to provide irritable bowel syndrome patients with long-lasting relief of their symptoms even after they stop taking the medication, according to a study published in the Jan. 6 issue of the New England Journal of Medicine.

Unlike in traditional therapies, such as when taking antidepressant and other medications that have benefits only while on the drug, patients in the study reported relief of their symptoms extended for weeks after completing treatment with rifaximin. Rifaximin is a minimally absorbed antibiotic that stays in the gut. Specifically, patients reported relief from bloating, less abdominal pain and improved stool consistency for up to 10 weeks.
While the concept of bacteria playing a key role in this condition was controversial when first unveiled a decade ago, this research confirms that bacteria in the gut, also known as "gut flora," trigger the symptoms of the chronic condition, affecting an estimated 30 million people in the United States.
These findings show that targeted antibiotics provide safe and effective long-lasting relief for this condition, said Mark Pimentel, M.D., GI Motility Program director and principal investigator of the clinical trials at Cedars-Sinai.
"For years, the treatment options for IBS patients have been extremely limited," Pimentel said. "IBS often does not respond well to treatments currently available, such as dietary changes and fiber supplements alone. With this antibiotic treatment, the patients feel better, and they continue to feel better after stopping the drug. This means that we did something to strike at the cause of the disease."
In two, 600-plus patient double-blind trials, IBS patients with mild to moderate diarrhea and bloating were randomly assigned to take a 550 milligram dose of rifaximin or placebo three times daily for two weeks. Study participants were then followed for 10 weeks more. About 40 percent of patients who took the drug reported they had significant relief from bloating, abdominal pain and loose or watery stools. Further, that relief was sustained for weeks after they stopped taking the antibiotic.
Doctors commonly categorize IBS patients with a "constipation predominant" condition, a "diarrhea-predominant" condition, or an alternating pattern of diarrhea and constipation. In addition, patients often experience abdominal pain or cramps, excess gas or bloating, and visible abdominal distension.
Because the cause of the disease had been elusive, treatments for the disease historically have focused on relieving its symptoms with medications that either slow or speed up the digestive process. Earlier research by Pimentel and colleagues documents a link between bloating, the most common symptom, and bacterial fermentation in the gut related to small intestine bacterial overgrowth, or SIBO.
Rifaximin is approved by the U.S. Food and Drug Administration to treat travelers' diarrhea and hepatic encephalopathy.
Besides Cedars-Sinai, other centers participating in the clinical trials included Beth Israel Deaconess Medical Center in Boston, University of Michigan Medical Center in Ann Arbor, University of North Carolina at Chapel Hill, and Connecticut Gastroenterology Institute in Bristol, Conn.
Rifaximin is marketed by Salix Pharmaceuticals Inc. Salix also provided funding for the studies. Pimentel discovered the use of rifaximin for IBS, and Cedars-Sinai holds patent rights to this discovery and has licensed rights to the invention to Salix. Dr. Pimentel is a consultant to Salix, Inc, and serves on its scientific advisory board.

 

[illsince1977]

A course of Rifaximin seemed to help my bloating (which was a fairly new symptom at the time, but I'm not eager to repeat it if the bloating returns as it may have precipitated severe constipation leading to nausea - I'm just not sure if it caused the problem or not). The bloating was highly uncomfortable and I feel terrible for anyone who suffers from this IBS symptom for years. I'm still afraid it will return. If indeed courses of Rifaxamin must be repeated every 6 months or so, it's definitely not really getting at the root of the problem. I wish I knew what was as I'm now experiencing a non-stop vaginal yeast infection and have grown intolerant of probiotics. I feel like I'm between a rock and a hard place - needing to adjust my gut flora as evidenced by the yeast infection, but not able to tolerate what it will take to do so.