Does XIFAXAN Get Rid of Bacteria? A Deep Dive Into Its Mechanism

October 14, 2025 •

4 min read

Affecting up to 15% of the US population, Irritable Bowel Syndrome (IBS) is a common functional bowel disease. For those with the diarrhea-predominant subtype (IBS-D), the question often arises: Does XIFAXAN get rid of bacteria to provide relief? The answer lies in its unique, gut-focused antibiotic action.

Quick Summary

XIFAXAN (rifaximin) is a gut-selective antibiotic that works by stopping bacterial growth in the intestines. It is used to treat traveler's diarrhea, IBS-D, and prevent hepatic encephalopathy by targeting specific gut bacteria.

Key Points

Targeted Action: XIFAXAN is a gut-selective antibiotic that is minimally absorbed into the bloodstream, allowing it to act directly in the intestines.
Mechanism: It works by stopping bacterial growth, binding to an enzyme in bacteria to inhibit their ability to produce essential proteins.
Primary Uses: XIFAXAN is FDA-approved to treat traveler's diarrhea caused by E. coli, Irritable Bowel Syndrome with Diarrhea (IBS-D), and to prevent the recurrence of hepatic encephalopathy.
Microbiome Impact: It helps rebalance the gut microbiome by reducing harmful bacteria, often with minimal disruption to the overall gut flora compared to systemic antibiotics.
Treatment Courses: Treatment is typically short-term for traveler's diarrhea and IBS-D, though it is used long-term for hepatic encephalopathy.
Safety Profile: Due to its low systemic absorption, XIFAXAN generally has fewer side effects than many other antibiotics; common side effects include nausea, headache, and dizziness.
Broad-Spectrum: It is effective against a wide range of gut bacteria, including both Gram-positive and Gram-negative types.

Understanding XIFAXAN (Rifaximin) and Its Role

XIFAXAN, the brand name for the drug rifaximin, is an oral antibiotic belonging to the rifamycin class of antimicrobials. What makes it unique is that it is a gut-selective antibiotic, meaning it is minimally absorbed into the bloodstream. Over 97% of the drug remains in the gastrointestinal tract and is excreted in the stool. This targeted action allows it to reach high concentrations directly where it's needed—in the gut—while minimizing systemic side effects that are common with other antibiotics.

How Does XIFAXAN Get Rid of Bacteria?

The primary mechanism of action for XIFAXAN is the inhibition of bacterial protein synthesis. It works by binding to the beta-subunit of the bacterial DNA-dependent RNA polymerase, which is an essential enzyme for bacteria to create the proteins they need to survive and multiply. By blocking this process, XIFAXAN effectively stops bacterial growth and spread.

XIFAXAN has broad-spectrum activity, meaning it is effective against a wide range of bacteria, including Gram-positive and Gram-negative, as well as aerobic and anaerobic types. This makes it effective for various gastrointestinal conditions where bacterial overgrowth or specific pathogens are a contributing factor.

FDA-Approved Uses for XIFAXAN

XIFAXAN is FDA-approved for three primary conditions:

Traveler's Diarrhea: It is used to treat traveler's diarrhea caused by noninvasive strains of Escherichia coli (E. coli) in adults and children 12 years and older. Treatment is typically for a short duration.
Irritable Bowel Syndrome with Diarrhea (IBS-D): For adults with IBS-D, XIFAXAN can provide relief from symptoms like abdominal pain and diarrhea. A typical treatment involves a specific course length. If symptoms recur, this course can be repeated up to two times. Clinical trials have shown that this treatment provides significant relief from IBS symptoms, including bloating and loose stools, for a period of time after treatment.
Overt Hepatic Encephalopathy (HE): XIFAXAN is used to reduce the risk of recurrence of overt HE, a brain function decline caused by severe liver disease. In this case, bacteria in the gut produce toxins like ammonia, which the damaged liver cannot filter out. By reducing these ammonia-producing bacteria, XIFAXAN helps lower the risk of HE episodes. This treatment is typically long-term.

It's also used "off-label" for conditions like Small Intestinal Bacterial Overgrowth (SIBO), where an excessive amount of bacteria in the small intestine causes symptoms like bloating and diarrhea.

Impact on the Gut Microbiome

A key aspect of XIFAXAN is its effect on the gut microbiome. Unlike some systemic antibiotics that can significantly disrupt the balance of gut flora, studies suggest XIFAXAN has a more modulatory effect. It works by reducing harmful bacteria to help rebalance the gut microbiome. Some research in animal models has even shown that rifaximin treatment can lead to a relative abundance of beneficial bacteria like Lactobacillus species while reducing others. This ability to target pathogenic bacteria with minimal impact on the overall composition of the gut flora is a distinct advantage.

Potential Side Effects

Because XIFAXAN is not significantly absorbed into the bloodstream, it generally has a favorable side effect profile. However, side effects can occur. The most common side effects depend on the condition being treated.

For Hepatic Encephalopathy (long-term use): Peripheral edema (swelling in limbs), dizziness, fatigue, and nausea are most common.
For IBS-D (short-term use): Nausea and an increase in liver enzymes are the most common side effects.
For Traveler's Diarrhea (short-term use): Headache is a commonly reported side effect.

In rare cases, more serious side effects can occur, including Clostridioides difficile (C. diff)-associated diarrhea, a severe gut infection that can be caused by antibiotic use.

XIFAXAN vs. Other Antibiotics


Feature	XIFAXAN (Rifaximin)	Other Systemic Antibiotics (e.g., Ciprofloxacin, Metronidazole)
Absorption	Minimally absorbed (<0.4%); acts locally in the gut	Systemically absorbed; distributed throughout the body
Spectrum	Broad-spectrum against gut pathogens	Broad-spectrum, affecting bacteria systemically
Side Effects	Generally fewer systemic side effects; localized to GI tract	Higher potential for systemic side effects (e.g., yeast infections, tendon issues with fluoroquinolones)
Impact on Microbiome	Modulates gut flora with minimal disruption; can promote some beneficial bacteria	Can cause significant disruption to the gut microbiome
Use Cases	FDA-approved for Traveler's Diarrhea (E. coli), IBS-D, and Hepatic Encephalopathy	Used for a wide range of bacterial infections throughout the body

Conclusion

So, does XIFAXAN get rid of bacteria? Yes, it is a potent antibiotic designed specifically to target and inhibit the growth of bacteria within the gastrointestinal tract. Its unique non-systemic nature makes it a highly effective and well-tolerated treatment for conditions like traveler's diarrhea and IBS-D, where gut bacteria play a significant role. By rebalancing the gut microbiome without causing major systemic disruption, XIFAXAN offers a targeted approach to managing complex gastrointestinal disorders.

For more information on the mechanism of rifaximin, you can visit the National Center for Biotechnology Information (NCBI).

Frequently Asked Questions

XIFAXAN (rifaximin) is a rifamycin antibiotic that is unique because it is minimally absorbed by the body and works almost exclusively in the gut to stop the growth of bacteria.

The time it takes for XIFAXAN to work depends on the condition. For traveler's diarrhea, symptoms may improve within a relatively short period. For IBS-D, it may take up to the completion of the prescribed course to experience symptom relief.

While XIFAXAN is not FDA-approved specifically for Small Intestinal Bacterial Overgrowth (SIBO), it is frequently prescribed 'off-label' for this condition, as it has been shown to be safe and effective in improving SIBO symptoms in studies.

XIFAXAN is designed to reduce harmful bacteria and help rebalance the gut microbiome. Unlike many systemic antibiotics, it has been shown to have minimal negative effects on the overall composition of the gut's normal flora and may even promote some beneficial bacteria.

For IBS-D, if your symptoms return after finishing the initial treatment, your doctor may prescribe the same treatment course again. You can be re-treated up to a certain number of times as directed by a healthcare professional.

Whether XIFAXAN is used long-term depends on the condition. It is used for short-term treatment for traveler's diarrhea and IBS-D. However, it is typically prescribed as a long-term maintenance therapy to prevent episodes of hepatic encephalopathy.

Common side effects vary by condition but can include nausea, headache, dizziness, fatigue, and swelling (peripheral edema). Side effects are generally mild because the drug stays within the gut.