What is Rifaximin (Rifamycin antibiotic)?

Rifaximin: A Nonabsorbable Rifamycin Antibiotic

Rifaximin is a nonabsorbable rifamycin antibiotic that acts by binding to bacterial DNA-dependent RNA polymerase, inhibiting bacterial protein synthesis, with primary applications in travelers' diarrhea, hepatic encephalopathy, and irritable bowel syndrome with diarrhea. 1

Pharmacological Properties

• Rifaximin is a semi-synthetic derivative of rifampin that inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase 1
• Less than 0.4% of the drug is absorbed after oral administration, allowing it to maintain high concentrations in the intestine until excretion 2, 3
• Average fecal concentration reaches approximately 8000 μg/g of stool after three days of therapy 3
• Rifaximin has a broad spectrum of antimicrobial activity against Gram-positive, Gram-negative, and anaerobic bacteria with MIC90 ranging between 32 and 64 μg/ml 3, 4

Clinical Applications

Travelers' Diarrhea

• FDA-approved for treatment of travelers' diarrhea caused by non-invasive diarrheagenic Escherichia coli at a dose of 200 mg three times daily for 3 days 1, 4
• Demonstrates comparable efficacy to fluoroquinolones in non-invasive TD caused by diarrheagenic E. coli 5
• Not recommended for areas where invasive pathogens (Campylobacter, Salmonella, Shigella) are common due to limited efficacy against these organisms 5
• Not appropriate for treatment of dysentery regardless of illness severity 5

Hepatic Encephalopathy

• Used for prevention of recurrent overt hepatic encephalopathy at doses of 400 mg three times daily or 550 mg twice daily 6, 2
• Studies show rifaximin is at least as effective as lactulose/lactitol and traditional antibiotics (neomycin, paromomycin) in improving neurologic symptoms and reducing blood ammonia levels 2

Irritable Bowel Syndrome with Diarrhea

• Standard dose for IBS-D is 550 mg three times daily for 14 days 6
• Can be taken with or without food 6

Safety Profile

• Rifaximin has an excellent safety profile due to minimal systemic absorption (<0.4%) 2, 3
• Has the best safety profile compared to other first-line antibiotics used for travelers' diarrhea 5
• Limited impact on intestinal microbiome compared to systemic antibiotics 4
• Development of significant bacterial resistance appears to be less common than with related drugs like rifampin 3
• No significant drug interactions with midazolam or oral contraceptives containing ethinyl estradiol and norgestimate 1

Limitations and Precautions

• Not effective against Campylobacter jejuni infections, which are common in Southeast and South Asia 5, 7
• Treatment failure rates up to 50% when used against invasive pathogens 5
• Should not be used for febrile invasive diarrheal disease 5
• Rifaximin prophylaxis has only moderate protective effectiveness in South and Southeast Asia where Campylobacteriosis is more common 5

Emerging Applications

• Small bowel bacterial overgrowth syndrome 3, 8
• Functional bloating 8
• Diverticular disease 8
• Inflammatory bowel disease 4, 8
• Pouchitis 8

Rifaximin represents an important therapeutic option for gastrointestinal disorders due to its unique properties of high intestinal concentration with minimal systemic absorption, resulting in excellent safety and tolerability profiles while maintaining broad-spectrum antimicrobial activity.