Rifaxamin

Here at The Functional Gut Clinic, we frequently see patients with irritable bowel syndrome (IBS), and a trial we conducted revealed that a significant proportion of IBS patients also have co-existing small intestinal bacterial overgrowth (SIBO).

One of the first line treatments for getting rid of SIBO is a 2-week course of the antibiotic, Rifaximin. However, this can be expensive and is not available to buy over the counter.

This blog aims to explore some of the earlier literature on Rifaximin, providing valuable insights into its mechanisms of action, the bacterial species it targets, its effects on the microbiome, microbial resistance, and any potential synergistic effects when combined with dietary interventions in conditions such as diverticulitis.

What is Rifaximin? 

Rifaximin is a semi-synthetic antibiotic derived from rifamycin, designed to achieve minimal gastrointestinal (GI) absorption while maintaining robust antibacterial activity. Both experimental and clinical pharmacological studies have demonstrated that Rifaximin is a poorly absorbed antibiotic with a broad spectrum of activity against both gram-positive, gram-negative, anaerobic and aerobic microorganisms.

Due to its targeted action within the intestinal lumen and its limited systemic absorption, Rifaximin is considered the preferred antibiotic for several GI conditions, including diarrhoea-predominant IBS (IBS-D), travelers’ diarrhoea, GI infections, diverticular disease, hepatic encephalopathy, pre- and post-surgical bowel preparation, Clostridium difficile infections, inflammatory bowel disease (IBD) and SIBO.

Mechanism of Action: How does Rifaximin work? 

Rifaximin is a bactericidal agent that exerts its effects by inhibiting bacterial RNA synthesis through irreversible binding to bacterial DNA-dependent RNA polymerase.

Its high efficacy is due in part to its elevated concentrations in the intestinal lumen, where its faecal concentrations are thousands of times greater than the Minimum Inhibitory Concentration (MIC90) for common pathogenic gut bacteria. The MIC90 is the lowest concentration of antimicrobial agent necessary to inhibit the growht of 90% of a bacterial population, which underscores Rifaximin’s potency against a broad range of pathogens in the GI tract.

Safety Profile of Rifaximin

Rifaximin is considered to be an exceptionally safe antibiotic for several reasons:

Firstly, it has minimal impact on the normal microbiome. Unlike most systemic antibiotics, Rifaximin does not significantly disrupt the microbiome. In fact, it has been shown to preserve the microbiome while increasing the relative abundance of beneficial gut bacteria such as Lactobacillus and Bifidobacteria, exhibiting a ‘eubiotic’ effect.

Secondly, there is a low risk of bacterial resistance. Rifaximin does not contribute to significant bacterial resistance. The high concentrations of Rifaximin in the gut create an environment that is unfavourable for the selection of resistant strains. Additionally, the resistance gene is chromosomal and non-transferable to other bacteria. As Rifaximin is not absorbed, it does not exert selective pressure on resistant strains in other organs. Any resistant strains that do emerge are typically unstable and unable to persist the GI tract after treatment is completed.

Rifaximin has been available for clinical use since the 1980s, with very few reports of adverse events, and no severe adverse effects have been documented.

Synergistic Effects of Rifaximin and Dietary Interventions in Diverticulitis

Studies have suggested that Rifaximin may work synergistically with a high-fibre diet in patients with non-complicated diverticular disease. Diverticulosis, characterised by the presence of diverticula (pouches) in the colon, is often asymptomatic. However, in approximately 20% of cases, patients may experience symptoms that significantly impact quality of life. When the diverticula become inflamed, known as diverticulitis, the condition becomes more serious, potentially requiring surgical intervention.

There is a growing body of evidence suggesting that reduced dietary fibre intake contributes to the development of diverticular disease. Furthermore, bacterial overgrowth in the diverticula has been implicated in the production of excessive gas, leading to symptoms such as bloating, abdominal pain, and low-grade inflammation.

The combination of dietary fibre and Rifaximin may be particularly effective in managing diverticular disease. Fibre can help to increase stool bulk and reduce intraluminal pressure, while Rifaximin may reduce bacterial overgrowth and its associated symptoms. Clinical trials have shown that the addition of cyclical Rifaximin treatment with fibre supplementation results in more effective symptom relief compared to fibre supplementation alone.

Indications for Rifaximin Use Globally

Rifaximin is available in over 30 countries under various brand names and pharmaceutical formulations, including 200mg tablets, 550mg tablet, and paediatric suspensions. Its clinical indications include:

• SIBO – we have a blog on this.

• IBS-D – we also have a blog on this.

• Traveller's Diarrhoea

• Acute GI Infections

• Diverticular Disease

• Hepatic Encephalopathy

• Pre- and Post-surgical Bowel Preparation

• Clostridium Diffcile Infections

Is Rifaximin available in the UK? 

In the UK, Rifaximin is marketed under the brand names Xifaxanta (200mg tablets) and Targaxan (550mg tablets). These are prescribed for the following conditions:

Traveler’s Dirrhoea – for adults aged 18 years and older, the recommended dose is 200mg every 8 hours for 3 days but only in those that do not present with fever, bloody diarrhoea, or significant inflammatory markers.

Hepatic Encephalopathy – for adults aged 18 years and older, the recommended dose is 550mg twice daily to reduce the recurrence of episodes.

The Bottom Line

In the UK, Rifaximin is marketed under the brand names Xifaxanta (200mg tablets) and Targaxan (550mg tablets). These are prescribed for the following conditions:

Traveler’s Dirrhoea – for adults aged 18 years and older, the recommended dose is 200mg every 8 hours for 3 days but only in those that do not present with fever, bloody diarrhoea, or significant inflammatory markers.

Hepatic Encephalopathy – for adults aged 18 years and older, the recommended dose is 550mg twice daily to reduce the recurrence of episodes.

REFERENCES:

1. Gatta, C. Scarpignato: Systematic review with meta-analysis: rifaximin is effective and safe for the treatment of small intestine bacterial overgrowth. Aliment Pharmacol Ther 2017; 45: 604–616

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.

3. Scarpignato C, Pelosini I. Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy 2005; 51(Suppl. 1): 36–66. 11.

4. Calanni F, Renzulli C, Barbanti M, Viscomi GC. Rifaximin: beyond the traditional antibiotic activity. J Antibiot 2014; 67: 667–70.

5. Jiang ZD, Dupont HL. Rifaximin: in vitro and in vivo antibacterial activity-a review. Chemotherapy 2005; 51(Suppl. 1): 67–72.

6. Adachi JA, Dupont HL. Rifaximin: a novel non-absorbed rifamycin for gastrointestinal disorders. Clin Infect Dis 2006; 42: 541–7.

7. Gillis J.C. et al. 1995; Vrijsen R. et al. 1992

8. Tripathi, K.D. (2013). Essentials of Medical Pharmacology (7th ed.). New Delhi, India: Jaypee Brothers Medical Publishers. pp. 696,697

9. Gillis et al, Drugs, 1995

10. Corazza GR, Di Stefano M, Scarpignato C. Treatment of functional bowel disorders: is there room for antibiotics? Digestion 2006; 73(Suppl. 1): 38–46.

11. Sullivan A, Edlund C, Nord CE. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect Dis 2001; 1: 101–14.

12. Maccaferri S, Vitali B, Klinder A, et al. Rifaximin modulates the colonic microbiota of patients with Crohn’s disease: an in vitro approach using a continuous culture colonic model system. J Antimicrob Chemother 2010; 65: 2556–65.

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