Description

Rifaximin is a synthetic, non-systemic antibiotic that belongs to the class of drugs known as rifamycins. Unlike other rifamycins that are used for systemic infections (e.g., tuberculosis), rifaximin is unique because it is minimally absorbed from the gastrointestinal (GI) tract. This means that after oral administration, it remains highly concentrated within the gut lumen, where it exerts its antibacterial effects with minimal systemic exposure.

Indications

Due to its poor systemic absorption, rifaximin is primarily indicated for the treatment and prevention of conditions caused by bacteria within the GI tract. Its key indications include:

• Traveler’s Diarrhea: It is used to treat traveler’s diarrhea caused by non-invasive strains of Escherichia coli in adults and children 12 years of age and older.

• Irritable Bowel Syndrome with Diarrhea (IBS-D): It is used for the treatment of IBS with diarrhea in adults. Its action on the gut flora helps to alleviate symptoms such as abdominal pain, bloating, and urgency.

• Hepatic Encephalopathy: It is used to reduce the risk of overt hepatic encephalopathy (HE) recurrence in adults. HE is a decline in brain function that occurs as a result of severe liver disease. Rifaximin works by reducing the production of ammonia and other neurotoxins by gut bacteria, which are implicated in the development of HE.

Mechanism of Action

Rifaximin’s mechanism of action is based on its ability to inhibit bacterial protein synthesis, but its effectiveness is tied to its unique pharmacokinetic property.

1. Targeting Bacterial RNA Polymerase: Rifaximin works by binding to the beta-subunit of the bacterial DNA-dependent RNA polymerase enzyme.

2. Blocking Transcription: By binding to this enzyme, rifaximin blocks the process of transcription, which is the first step in bacterial protein synthesis. This action prevents the bacterial cell from creating essential proteins and enzymes, leading to the cessation of bacterial growth and proliferation (bacteriostatic effect) or, at higher concentrations, bacterial death (bactericidal effect).

3. Localized Action: The most crucial aspect of rifaximin’s mechanism is its minimal systemic absorption. After oral administration, over 99% of the dose remains in the gastrointestinal tract. This high luminal concentration allows the drug to effectively target and eliminate susceptible bacteria within the gut while having a very low risk of systemic side effects or contributing to widespread antibiotic resistance in other parts of the body.