At the Functional Gut Clinic we see many patients with IBS and our recent clinical trial showed that a large proportion of IBS patients have co-existent small intestinal bacterial overgrowth (SIBO).

As the Functional Gut Clinic predominantly sits in the private sector, many patients that we diagnose with SIBO go on to be successfully treated with Rifaxamin. The problem being that they usually pay for themselves at around £300 for a two-week course.

We would really like to help build the case with other healthcare professional to make Rifaxamin more widely available to patients beyond the private sector but before doing so I was struck by the relative paucity of information about how Rifaxamin works.

Fortunately, our new colleague at Functional Gut Diagnostics Ltd, Federico Moschini, is here to help out. Federico is from a pharmacology background and has great experience with Rifaxamin.

This blog reviews some of the older literature on Rifaxamin which have been somewhat lost to is as a community and provides some important insights into how Rifaxamin works, which bacterial species it is effective against, it’s effect on the microflora / resistance and potential synergies in certain conditions like diverticulitis when used with dietary interventions.

We hope you find this of interest and would love to hear your thoughts on this interesting topic,

What is Rifaximin? 

Rifaximin is a product of synthesis experiments designed to modify the parent compound, rifamycin, to achieve low gastrointestinal absorption while retaining good antibacterial activity (1-4). Both experimental and clinical pharmacology have clearly shown that this compound is a poorly absorbed antibiotic with a broad spectrum of antibacterial activity, covering Gram-positive and Gram-negative microorganism, both aerobes and anaerobes (3-6).

Thanks to its targeted action in the intestinal lumen, Rifaximin is the non-absorbable antibiotic of choice for several gastrointestinal diseases like: diarrhea predominant irritable bowel syndrome (IBS-D), travelers’ diarrhea, gastrointestinal infections, diverticular disease, hepatic encephalopathy, pre and post-surgery preparation of the bowel, Clostridium Difficile infections, IBD and SIBO (Small Intestine Bacterial Overgrowth).

How does Rifaximin work? 

Rifaximin is a bactericidal agent that kills bacteria by inhibiting their RNA synthesis; this is possible thanks to an irreversible binding to the bacterial DNA-dependent RNA polymerase (7).

Due to this effective mechanism of action and to the fact that its action is targeted in the gut for its poor systemic absorption, Rifaximin fecal concentration exceeds thousands of times the MIC90 of the main pathogenic intestinal bacteria. The minimum inhibitory concentration (MIC) is the lowest concentration of a chemical (Rifaximin in this case) necessary to inhibit the growth of the 90% of a bacterium (8); this means that Rifaximin is highly effective against all these different common pathogens:

Is Rifaximin a safe intestinal antibiotic?

Rifaximin is considered an extremely safe drug for several reasons:

  1. It does not affect the normal intestinal microflora (as the most common systemic antibiotics do) (9-11). As you can observe by the image here below, the normal flora spontaneously regenerates after a treatment course with Rifaximin: (9). Furthermore, it has been found that rifaximin is able to preserve colonic flora and increases the relative abundance of Lactobacilli and Bifidobacteria, showing an ‘eubiotic’ effect (increasing the concentration of the “good bacteria”) (12, 13).
  2. Rifaximin does not induce significant bacterial resistance, this means that keeps its effectiveness high. This is for several reasons (14)
    A: The high concentrations reached by Rifaximin in the intestine is a condition not favorable to the selection of resistant strains.
    B: The resistance gene to Rifaximin is chromosomal, therefore it is not transferred to other bacteria.
    C: Rifaximin is not absorbed, so that it does not exert a selective pressure to resistant strains in other organs.
    D: Resistant strains disappear from the intestine after finalizing the treatment, because they are unstable and unable to colonize the gastrointestinal tract (see picture below)
  3. Rifaximin is on the market since the 80’ and very few and not severe adverse events (AEs) have been reported.

Diet & Rifaximin in Divericulitis: are there any synergies?

Many studies showed a synergy between Rifaximin and a diet high in fibers intake in non-complicated diverticular disease patients (15,16). Diverticular disease, or diverticulosis, is the condition of having multiple pouches (diverticula) in the colon that are not inflamed. These are out pockets of the colonic mucosa and submucosa through weaknesses of muscle layers in the colon wall [17]. They typically cause no symptoms but a 20% of these patients is symptomatic with a significant impact also in their quality of life [15,16]. When the diverticula become inflamed, known as diverticulitis, the disease becomes a more serious condition where bleeding and eventually perforation can occur. Diverticulitis often requires an emergency surgery of the colon to remove the diverticula (18).

Geographic correlations and time trend analyses suggest that the condition is caused by reduced intake of dietary fiber, a hypothesis supported by experimental, epidemiological and therapeutic studies. Bacterial overgrowth has also been observed at least in a group of diverticular disease patients, a condition that may allow an excessive production of bowel gas with secondary development of abdominal pain, bloating and tenderness as well as a low grade inflammation (15,16).

The efficacy of dietary fiber in the relief of pain and bowel dysfunction in uncomplicated diverticular disease has been held to be related to their capacity to hold water, to increase intraintestinal content mass, to relax the intestinal wall, and to lower the intraluminal pressure.

The mechanism by which rifaximin improves symptoms in uncomplicated diverticular disease is unclear. It has been suggested a synergistic effect of Rifaximin and high fiber diet in reducing proliferation of gut microflora, with a consequent decrease in bacterial gases production (hydrogen and methane) and/or in expanding fecal mass due to a decrease in bacterial degradation of the fibers.

Furthermore, Rifaximin may improve symptoms and lower the frequency of disease complications reducing intestinal bacterial overgrowth [15,16].

Clinical trials showed that addition of cyclic administration of rifaximin to fiber supplementation is more effective in obtaining symptom relief in patients with uncomplicated diverticular disease than fiber supplementation alone, confirming previous observations reported by others (15, 16).

What are the indications of Rifaximin around the world? 

Rifaximin is available in more than 30 countries around the world under different commercial brand names and pharmaceutical presentations (200mg tablets, 550mg tablets, suspension for pediatric use). The indications of use are:

  • SIBO (Small Intestine Bacterial Overgrowth): we will dedicate an article to this topic
  • IBS-D (Irritable Bowel Syndrome diarrhea predominant): we will dedicate an article to this topic
  • travelers’ diarrhea
  • acute gastrointestinal infections
  • diverticular disease
  • hepatic encephalopathy
  • pre and post-surgery preparation of the bowel
  • Clostridium Difficile infections

Is Rifaximin available in the UK? 

Rifaximin is available in the UK under the names of Xifaxanta (200mg tablets presentation) and Targaxan (550mg tablets presentation) for the following indications and dosages (19):

  • Travellers’ diarrhoea that is not associated with fever, bloody diarrhoea, blood or leucocytes in the stool, or 8 or more unformed stools in the previous 24 hours, ADULT over 18 years, 200 mg every 8 hours for 3 days
  • Reduction in recurrence of hepatic encephalopathy, ADULT over 18 years, 550 mg twice daily

Although Rifaxamin is not licensed for IBS-D and SIBO usage in the UK it is often prescribed by private prescription by GMC registered Consultants. We hope that our continuing clinical trial work will help to support the use of this undoubtedly safe and effective drug here in the UK.


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  2. Marchi E, Montecchi L, Venturini AP, Mascellani G, Brufani M, Cellai L. 4Deoxypyrido[1’,2’:1,2]imidazo[5,4-c] rifamycin SV derivatives. A new series of semisynthetic rifamycins with high antibacterial activity and low gastroenteric absorption. J Med Chem 1985; 28: 960–3. 10.
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  13. Ponziani FR, Scaldaferri F, Petito V, et al. Rifaximin treatment increases lactobacillus abundance in patients with different gastrointestinal and liver diseases. UEG Journal 2015; 3(5S): A138. Pimentel, et al. Am J Physiol, 2006
  14. De Leo et al., Drugs Exptl Clin Res 1986; 12: 979-981
  15. Latella et al., Rifaximin improves symptoms of acquired uncomplicated diverticular disease of the colon. Int J Colorectal Dis (2003) 18:55–62 DOI 10.1007/s00384-002-0396-5
  16. Colecchia et al., Efficacy of long term cyclic administration of the poorly absorbed antibiotic Rifaximin in symptomatic, uncomplicated colonic diverticular disease. World J Gastroenterology 2007 January 14; 13(2): 264-269
  17. Feuerstein, JD; Falchuk, KR (August 2016). “Diverticulosis and Diverticulitis”. Mayo Clinic Proceedings (Review). 91 (8): 1094-1104. PMID 27156370. doi:10.1016/j.mayocp.2016.03.012
  18. Review article: the pathophysiology and medical management of diverticulosis and diverticular disease of the colon. Tursi A1, Papa A2, Danese S3. http://onlinelibrary.wiley.com/doi/10.1111/apt.13322/abstract
  19. https://www.evidence.nhs.uk/formulary/bnf/current/5-infections/51-antibacterial-drugs/517-some-other-antibacterials/rifaximin/rifaximin