Is there any merit in retreating small intestinal bacterial overgrowth (SIBO) with a second round of Rifaximin (rifamycin derivative)?

From the Guidelines

There is merit in retreating small intestinal bacterial overgrowth (SIBO) with a second round of Rifaximin, as suggested by the American Gastroenterological Association (AGA) in their 2022 clinical practice guideline 1. For patients who initially respond to Rifaximin but experience symptom recurrence, a repeat course of the same antibiotic is often effective. The typical retreatment regimen remains 550 mg three times daily for 14 days, the same as the initial treatment. Some clinicians may consider adding neomycin (500 mg twice daily) alongside Rifaximin if methane-predominant SIBO is suspected, as this combination targets different bacterial populations. Retreatment is particularly appropriate when patients experienced clear symptom improvement during the first course. The rationale for retreatment is that SIBO frequently recurs due to underlying conditions that promote bacterial overgrowth, such as altered motility, anatomical abnormalities, or immunological factors. Rifaximin works well for retreatment because it has minimal systemic absorption, acts locally in the intestine, and has a low risk of developing bacterial resistance compared to other antibiotics, as noted in the management of adult patients with severe chronic small intestinal dysmotility 1. For patients with multiple recurrences, addressing the underlying cause of SIBO and considering prokinetic agents after antibiotic therapy may help prevent further episodes. Key points to consider when retreating SIBO with Rifaximin include:

• The AGA suggests retreatment with Rifaximin in patients with IBS-D who develop recurrent symptoms after an initial response 1
• Rifaximin has a broad spectrum of activity against both gram-negative and gram-positive anaerobic and aerobic bacteria
• The typical dosage regimen for retreatment is 550 mg three times daily for 14 days
• Patients can be retreated up to 2 times with the same dosage regimen 1

From the FDA Drug Label

Table 8 Efficacy Responder Rates in Trial 3 in a Given Week for at Least 2 Weeks During Weeks 3 to 6 of the Double-Blind, First Repeat Treatment Phase Placebo (n=308) n (%) XIFAXAN (n=328) n (%) Treatment Difference (95% CIa) Combined Responderb: Abdominal Pain and Stool Consistency Respondersc 97(31) 125(38) 7%(0.9%,16.9%) Abdominal Pain Responders (≥30% reduction in abdominal pain) 130(42) 166(51) 9%(1. 6%,17.0%) Stool Consistency Responders (≥50% reduction from baseline in days/week with loose or watery stools) 154(50) 170(52) 2%(-4.7%,11. 0%)

There is some merit in retreating small intestinal bacterial overgrowth (SIBO) with a second round of Rifaximin, as shown by the results of Trial 3, where more patients receiving XIFAXAN were monthly responders for abdominal pain and stool consistency in the primary analysis 2. The treatment difference for combined responders was 7% (0.9%, 16.9%) in favor of XIFAXAN. However, the clinical relevance of these findings should be considered on a case-by-case basis, taking into account the individual patient's response to initial treatment and the risk of developing resistance to rifaximin.

From the Research

Rifaximin Retreatment for SIBO

• There is limited research on the effectiveness of a second round of rifaximin for treating small intestinal bacterial overgrowth (SIBO) 3, 4, 5, 6, 7.
• A 2014 study found that herbal therapy was equivalent to rifaximin for the treatment of SIBO, with 34% of rifaximin users achieving a negative follow-up lactulose breath test (LBT) compared to 46% of herbal therapy users 3.
• A 2020 review noted that the mainstay of treatment for SIBO is antibiotics, but alternative therapies such as herbal medications, dietary modifications, and prokinetic agents may also be effective 5.
• A 2024 study found that rifaximin may be beneficial in alleviating SIBO and reducing small intestinal gas volume in SIBO-positive patients with chronic intestinal pseudo-obstruction, with a 75% SIBO eradication rate in the rifaximin group 6.
• The 2020 AGA Clinical Practice Update on SIBO recommends that management should focus on identifying and correcting underlying causes, correcting nutritional deficiencies, and administering antibiotics, but notes that there is a limited database to guide antibiotic strategies for SIBO 7.

Considerations for Rifaximin Retreatment

• The decision to retreat with rifaximin should be based on individual patient factors, such as the presence of ongoing symptoms and the results of diagnostic testing 3, 4, 5, 6, 7.
• Patients who do not respond to initial rifaximin treatment may be considered for alternative therapies, such as herbal medications or prokinetic agents 3, 5.
• The potential risks and benefits of long-term broad-spectrum antibiotic therapy should be carefully considered when developing treatment strategies for SIBO 7.