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Rifaximin

Minimally absorbed oral antibiotic concentrated in the gastrointestinal tract.

A structural analog of rifampin that inhibits the synthesis of bacterial RNA by binding to the beta subunits of bacterial DNA-dependent RNA polymerase.

Trade name Xifaxan.

Has broad spectrum activity against gram positive and gram negative areobic and anaerobic organisms.

Has complex mechanisms of action which include direct antimicrobial effects, inhibition of bacterial translocation across the gut mucosa and subsequent alteration in the release and or absoption of endotoxin and bacterial metabolites, and modulates gut-immune signaling.

Indicated for the treatment of travelers’ diarrhea caused by noninvasive E.coli strains and also for reducing the risk of recurrence of hepatic encephalopathy .

Has a low risk of inducing bacterial resistance.

More effective than lactulose in the treatment of hepatic encephalopathy, and has an efficacy equal to or better than other oral antibiotics in this process.

Rifaximin, an oral, nonsystemic, broad-spectrum antibiotic targets the gastrointestinal tract and is associated with low risk of bacterial resistance: in double blind trials (TARGET 1 and TARGET 2) treating patients with IBS without constipation for 2 weeks with rifaximin provided relief of symptoms, bloating, abdominal pain, and loose or watery stools (Pimentel M et al).

Treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with rifaximin is associated with significant symptomatic improvements.

Improve symptoms of IBS through its modulation of the gut microbiota and host interactions, including treating SIBO via antimicrobial activity, inhibiting bacterial translocation, and altering inflammatory responses.

The development of C difficile infection after the administration of nonsystemic rifaximin is rare.

In the TARGET 3 study that included 2,579 patients, 42% of patients responded to 2 weeks of treatment with of at least a 30% reduction in pain and a 50% or greater decrease in the number of days with scores or 6 (loose) or 7 (watery) on the Bristol Stool Scale.

In the above study 36% of initial responders never relapsed over 18 to 22 weeks of follow-up.

Of the 64% who did relapse that were randomized to a second blinded 2-week course of treatment or placebo, 33% on rifaximin again responded compared with 25% of those receiving placebo.

Of those who again relapsed were re-randomized to the active treatment or placebo, and 37% of the rifaximin group responded compared with 29% of the placebo group.

Study suggested patients with IBS retreated with Rifaximin continue to have benefit.

As a result of above study, it is now believed that a substantial number of patients with IBS have increased microbes in the small intestine.

In the TARGET-3 study the administration of rifaximin, 550 mg three times daily for 2 weeks, followed by a 4-week treatment-free phase during which efficacy was assessed.

In TARGET 3! those who underwent retreatment after symptoms recurred were mostly women, whose mean age was 47.

In the above study gene sequencing and cultures with antibiotic susceptibility testing showed that three courses of treatment led to no changes in bacterial sensitivity and no cross-resistance to other agents.

Dose 550 mg BID.

Headache is the most common adverse event.

Most commonly reported AEs included headache, upper respiratory tract infection, and nausea.

C.difficle associated diarrhea does not occur with use.

After only 10 days of treatment with systemic antibiotics, the gut microbiota can be altered for up to 1 year.

A single and the repeat 2-week courses of nonsystemic rifaximin had minimal effects on the gut microbiota of patients with IBS-D.

Long term use is not associated with fecal bacterial antibiotic resistance.

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