Treatment Of Small Intestinal Bacterial Overgrowth Research Articles

Breath Testing for Small Intestinal Bacterial Overgrowth: Maximizing Test Accuracy

The diagnosis of small intestinal bacterial overgrowth (SIBO) has increased considerably owing to a growing recognition of its association with common bowel symptoms including chronic diarrhea, bloating, abdominal distention, and the irritable bowel syndrome. Ideally, an accurate and objective diagnosis of SIBO should be established before initiating antibiotic treatment. Unfortunately, no perfect test exists for the diagnosis of SIBO. The current gold standard, small-bowel aspiration and quantitative culture, is limited by its high cost, invasive nature, lack of standardization, sampling error, and need for dedicated infrastructure. Although not without shortcomings, hydrogen breath testing provides the simplest noninvasive and widely available diagnostic modality for suspected SIBO. Carbohydrates such as lactulose and glucose are the most widely used substrates in hydrogen breath testing, with glucose arguably providing greater testing accuracy. Lactose, fructose, and sorbitol should not be used as substrates in the assessment of suspected SIBO. The measurement of methane in addition to hydrogen can increase the sensitivity of breath testing for SIBO. Diagnostic accuracy of hydrogen breath testing in SIBO can be maximized by careful patient selection for testing, proper test preparation, and standardization of test performance as well as test interpretation.

Rifaximin in irritable bowel syndrome: rationale, evidence and clinical use

Irritable bowel syndrome (IBS) is the most common functional bowel disease that affects up to 15% of the US population. The majority of patients with IBS have significant bloating and gas. Recent evidence is beginning to suggest that patients with IBS may have an alteration in the gastrointestinal flora. Specifically, findings suggest that patients with IBS have excessive bacteria in the small bowel, referred to as bacterial overgrowth. Therefore there may be benefits of antibiotic-based therapies for IBS. Rifaximin is a nonabsorbable antibiotic that demonstrates no clinically relevant bacterial resistance. Some studies have demonstrated the efficacy and durable improvement of IBS symptoms after treatment with rifaximin. In this review we explore the current data showing the association of small intestinal bacterial overgrowth (SIBO) and IBS as well as review the available data on the clinical use of rifaximin in the treatment of SIBO in patients with IBS.

Probable Interaction Between Warfarin and Rifaximin in a Patient Treated for Small Intestine Bacterial Overgrowth

To report a case in which the anticoagulant effects of warfarin were attenuated during concomitant administration of rifaximin, possibly through induction of CYP3A4 following increased absorption of rifaximin in a patient with small intestine bacterial overgrowth (SIBO). A 49-year-old African American female had received effective anticoagulant therapy for 5 months with a target international normalized ratio (INR) of 2.0-3.5 on a warfarin regimen of 7.5 mg daily. Five days following initiation of rifaximin 400 mg 3 times daily to treat SIBO, her INR had fallen to 1.2 and remained suppressed throughout the duration of her rifaximin regimen despite incremental warfarin dosage increases (highest dose, 15 mg/day for 2 days, followed by 11.25 mg/day). Twelve days after completion of the rifaximin treatment course, the INR was supratherapeutic at 4.2, requiring titration to her baseline warfarin dosage to achieve an INR within the target range. Similar results were obtained following rechallenge with rifaximin. Rifaximin has been shown in vitro to induce the CYP3A4 enzyme for which the R-isomer of warfarin is a known substrate. The lack of in vivo CYP3A4 induction with rifaximin in other patient populations has repeatedly been attributed to its minimal oral bioavailability, while a recent study found that patients with SIBO had a clinically significant increase in intestinal permeability. In this patient population it is plausible that rifaximin bioavailability increases enough to induce CYP3A4, leading to clinically significant reductions in the bioavailability of CYP3A4 substrates, including R-warfarin. An objective causality assessment of this case revealed that a warfarin-rifaximin interaction was probable. No other drug dosages were altered during the timeframe in question, and the patient had an impeccable medication adherence history; we therefore ruled out these potential etiologies. To our knowledge, an interaction between warfarin and rifaximin has not been previously reported. While further research needs to be conducted to confirm these results, practitioners should be aware of this possibility because of the increasing use of rifaximin as a first-line choice in the treatment of SIBO.

Clinical trial: the combination of rifaximin with partially hydrolysed guar gum is more effective than rifaximin alone in eradicating small intestinal bacterial overgrowth

Abnormal intestinal clearance is involved in the pathogenesis of small intestinal bacterial overgrowth (SIBO). It is known that partially hydrolysed guar gum affects intestinal motility. Eradication therapy of SIBO is based on antibiotic treatment: no data are available on the role of fibre supplementation in eradicating SIBO. To assess whether the combination of partially hydrolysed guar gum and rifaximin is more effective than rifaximin alone in the treatment of SIBO. A 50 g-glucose breath test was given to 500 consecutive patients. Patients with a positive glucose breath test and predisposing conditions to SIBO entered into the study, and were randomized to receive rifaximin 1200 mg/day or rifaximin 1200 mg/day plus partially hydrolysed guar gum 5 g/day for 10 days. Patients completed a symptom questionnaire and glucose breath test both in basal condition and 1 month after withdrawal of therapy. Seventy-seven patients had SIBO. Eradication rate of SIBO was 62.1% in the rifaximin group (both on per-protocol and intention-to-treat analyses), and 87.1% (per-protocol, P=0.017) and 85.0% (intention-to-treat, P=0.036) in the rifaximin-plus-partially hydrolysed guar gum group. Clinical improvement was observed in 86.9% and 91.1% of eradicated cases in rifaximin and rifaximin-plus-partially hydrolysed guar gum groups respectively (P=0.677). The combination of rifaximin with partially hydrolysed guar gum seems to be more useful in eradicating SIBO compared with rifaximin alone.

Review of rifaximin as treatment for SIBO and IBS

Background: Rifaximin is a broad-range, gastrointestinal-specific antibiotic that demonstrates no clinically relevant bacterial resistance. Therefore, rifaximin may be useful in the treatment of gastrointestinal disorders associated with altered bacterial flora, including irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). Objective: To review rifaximin for treatment of IBS and SIBO. Methods: Review of rifaximin clinical trials. Results/conclusion: Rifaximin improved global symptoms in 33 – 92% of patients and eradicated SIBO in up to 84% of patients with IBS, with results sustained up to 10 weeks post-treatment. Rifaximin caused a lower number of adverse events compared with metronidazole or levofloxacin and may have a more favorable adverse event profile than systemic antibiotics, without clinically relevant antibiotic resistance.

Small intestine bacterial overgrowth and irritable bowel syndrome-related symptoms: Experience with Rifaximin

To estimate the prevalence of small intestinal bacterial overgrowth (SIBO) in our geographical area (Western Sicily, Italy) by means of an observational study, and to gather information on the use of locally active, non-absorbable antibiotics for treatment of SIBO. Our survey included 115 patients fulfilling the Rome II criteria for diagnosis of irritable bowel syndrome (IBS); a total of 97 patients accepted to perform a breath test with lactulose (BTLact), and those who had a positive test, received Rifaximin (Normix, Alfa Wassermann) 1200 mg/d for 7 d; 3 wk after the end of treatment, the BTLact was repeated. Based on the BTLact results, SIBO was present in about 56% of IBS patients, and it was responsible for some IBS-related symptoms, such as abdominal bloating and discomfort, and diarrhoea. 1-wk treatment with Rifaximin turned the BTLact to negative in about 50% of patients and significantly reduced the symptoms, especially in those patients with an alternated constipation/diarrhoea-variant IBS. SIBO should be always suspected in patients with IBS, and a differential diagnosis is done by means of a "breath test". Rifaximin may represent a valid approach to the treatment of SIBO.

A Retrospective Study of Small Intestinal Bacterial Overgrowth in Patients with Bloating

Purpose: Many patients (80–90%) with IBS consider bloating their most bothersome symptom. Recent studies suggest a link between abdominal bloating and/or irritable bowel syndrome (IBS) and small intestinal bacterial overgrowth (SIBO). The prevalence of SIBO in patients with bloating, with or without IBS, is unknown. We determined the prevalence of SIBO in patients referred for lactulose breath test (LBT) and response to treatment for SIBO in patients with bloating. Methods: Selection criteria for enrollment included; >18 years of age and LBT with bloating as a symptom at the UUHSC from Jan 2004 to May 2007. A chart review was performed to collect information including; indication for LBT, LBT results, presence or absence of IBS and treatment and response. SIBO was diagnosed by LBT. An LBT positive result was defined as an early rise (<90 min) in hydrogen (>20 ppm) or methane (>12 ppm). IBS was diagnosed clinically. A positive response was defined as moderate or greater improvement by patient or physician subjective criteria. Chi square or Fisher's exact test were used to make comparisons between groups. Results: A total of 255 breath tests were performed. There were 169 patients with bloating as a symptom (9 with no result). The mean age for patients with bloating was 47.6 years ± 15.8, 69% were female. The prevalence of positive SIBO in patients with bloating was 51% (82/160). The prevalence of positive SIBO was different between patients referred for bloating vs. referred for other reasons ((82/160 (51%) vs. 27/86 (31%), P= 0.004)). The prevalence of positive SIBO in patients with bloating and IBS was 22/42 (52%). There was no difference in the prevalence of SIBO in patients with and without IBS ((22/42 (52%) versus 62/118 (46%) P= NS)). 82% (28/34) of patients with bloating and positive LBT responded to antibiotic treatment vs. 33% (3/9) of patients with bloating and negative LBT (P= 0.008, OR = 9.3). Patients were followed for 10.4 ± 7.7 months for response. Conclusion: In patients with bloating referred for LBT, SIBO positivity was significantly higher than in patients referred for other reasons. In patients with bloating, SIBO positivity was not different in patients with and without IBS. Patients with bloating and positive SIBO by LBT are significantly more likely to respond to antibiotic Rx than patients with bloating and negative SIBO by LBT. Further investigation of factors associated with bloating, SIBO and response to antibiotic therapy is warranted.

Rifaximin Treatment for Symptoms of Irritable Bowel Syndrome

To evaluate the role of rifaximin in the treatment of symptoms associated with irritable bowel syndrome (IBS). Clinical literature was accessed through MEDLINE (1990-September 2007) using the terms rifaximin, small intestinal bacterial overgrowth (SIBO), bacterial overgrowth, and irritable bowel syndrome. Additionally, references in publications identified in the search were reviewed for relevant information. All articles published in English identified from the data source were evaluated. Randomized clinical trials in adult populations were included. IBS is a common functional bowel disorder of unknown etiology. Some evidence suggests that symptoms are secondary to bacterial overgrowth in the small intestine. Rifaximin, a nonsystemic antibiotic that targets the gastrointestinal tract, has been evaluated in the treatment of SIBO. Six studies that evaluated rifaximin in either IBS, with or without documented SIBO, or SIBO alone, were reviewed. Significant symptom improvement was reported, and in some cases, correlated with reductions in hydrogen breath tests, suggesting successful treatment of bacterial overgrowth. Data are limited by controversial diagnostic techniques for SIBO, small sample sizes, the unpredictable course of the disorder, and variability in clinical trial methodology that prevents direct comparison. Rifaximin offers a potential new therapeutic option for patients with refractory IBS. Larger, well-designed trials are necessary to elucidate the role of rifaximin in the treatment of this disorder.

Calcium Deficiency Is Associated with Small Intestinal Bacterial Overgrowth after Roux-en-Y Gastric Bypass Surgery

Purpose: We have shown that after Roux-en-Y gastric bypass surgery (GBS), patients frequently have elevated serum folate levels, a marker of small intestinal bacterial overgrowth (SIBO). Gastric pouch achlorhydria after GBS may lead to SIBO. Calcium deficiency with subsequent hyperparathyroidism and decreased bone mineral density has been reported after GBS. We hypothesize that by altering gut ecology, GBS induces calcium deficiency. Methods: This is a retrospective chart review of 452 patients who underwent Roux-en-Y gastric bypass surgery from 1999–2005. Of these patients, 154 had determination of serum folate, serum calcium, and 24 hour urinary calcium levels. Baseline patient demographics and characteristics included age, sex, and BMI. Glucose-hydrogen breath testing (HBT) had been performed in 43 patients (abnormal test was: hydrogen concentration >15 ppm over baseline fasting value or fasting hydrogen level >10 ppm). Results: In 129 female and 25 male patients, average age was 42 years (21 to 63 years) with BMI range of 40 to 80 kg/m2. Among 43 patients who underwent HBT, 42 had an abnormal breath test. Of these 42 patients, 38 also had elevated serum folate (90% sensitivity for elevated serum folate as a predictor of SIBO). Of 42 patients with abnormal HBT, 30 had low 24 hour urinary calcium (Chi-squared 2 × 2: P < .01). In the154 patients, 48 patients had normal serum folate levels of whom 38 had normal urinary calcium; in 106 patients with elevated serum folate, 80 had low 24 hour urinary calcium (Chi-squared 2 × 2: P < .001). Corrected serum calcium was within the normal range in all patients. Conclusion: Using HBT as the gold standard, almost all GBS patients who were tested had abnormal HBT, supporting the belief that SIBO is common after GBS. Elevated serum folate has a high sensitivity for detecting SIBO. Serum calcium determination is not accurate in predicting calcium metabolism in these patients. This study supports our hypothesis that by altering gut ecology, GBS induces calcium deficiency. Calcium malabsorption and secondary hyperparathyroidism may increase the risk for developing osteopenia, osteoporosis, and ultimately osteomalacia. Further studies of calcium metabolism after treatment of SIBO may support a treatment option for these patients.

Nitazoxanide for the Treatment of SIBO Related Gastrointestinal Symptoms in Pediatric Population

Purpose: Many pediatric patients present with symptoms of Small Intestinal Bacterial Overgrowth (SIBO). Intestinal anaerobic bacteria are known to contribute to the symptoms exhibited by these patients. However, without a definitive test to confirm SIBO, many pediatric practitioners empirically treat these patients with a course of antibiotics with or without probiotics. Nitazoxanide (NTZ) is a first in class thiazolide antibiotic with a targeted anaerobic antibacterial activity, placebo-like safety profile, high gastrointestinal (GI) concentration, and has limited to no activity against probiotic species. To date no studies have evaluated the empiric use of NTZ for the treatment of GI related symptoms in pediatric SIBO patients. Methods: A chart review was performed on patients treated with NTZ from February 2006 to May 2007. The diagnosis of SIBO was made by the attending physician based on the patient's history, signs and symptoms. Efficacy was measured as resolution of the patient's GI related symptoms, 3–8 weeks after the end of therapy. Primary markers for resolution included: abdominal pain, diarrhea, constipation, bloating, and/or flatulence. Overall 22 patients met the inclusion criteria for review. Results: Of the 22 patients treated with NTZ, 13 (median age – 6.8 years) patients returned to the office for adequate follow up. Nine patients were prescribed NTZ for SIBO and have not returned to the office for any GI complaints. The range of NTZ doses used was 100 mg – 500 mg BID for 5–10 days depending on age of the pediatric patient. The mean dose and duration was 422 mg/d for 7.7 days. The most common dose was 200 mg BID for 10 Days (N = 5). All patients treated with NTZ and a probiotic (13/13 [100%]) had complete resolution of symptoms that were present at initial visit. No clinically significant adverse reactions attributable to NTZ were identified during the study. Conclusion: Nitazoxanide appears to be a safe and effective therapy for the empiric treatment of SIBO related GI symptoms in pediatric patients. Larger controlled clinical trials are warranted to support these findings.Table. Results

High dosage rifaximin for the treatment of small intestinal bacterial overgrowth

Rifaximin is a broad spectrum non-absorbable antibiotic used for treatment of small intestinal bacterial overgrowth. Doses of 1200 mg/day showed a decontamination rate of 60% with low side-effects incidence. To assess efficacy, safety and tolerability of rifaximin 1600 mg with respect to 1200 mg/day for small intestinal bacterial overgrowth treatment. Eighty consecutive small intestinal bacterial overgrowth patients were enrolled. Diagnosis of small intestinal bacterial overgrowth based the clinical history and positivity to H(2)/CH(4) glucose breath test. Patients were randomized in two 7-day treatment groups: rifaximin 1600 mg (group 1); rifaximin 1200 mg (group 2). Glucose breath test was reassessed 1 month after. Compliance and side-effect incidence were also evaluated. One drop-out was observed in group 1 and two in group 2. Glucose breath test normalization rate was significantly higher in group 1 with respect to group 2 both in intention-to-treat (80% vs. 58%; P < 0.05) and per protocol analysis (82% vs. 61%; P < 0.05). No significant differences in patient compliance and incidence of side effects were found between groups. Rifaximin 1600 mg/day showed a significantly higher efficacy for small intestinal bacterial overgrowth treatment with respect to 1200 mg with similar compliance and side-effect profile.

Are higher doses of rifaximin more effective for the treatment of small-intestinal bacterial overgrowth?

Are higher doses of rifaximin more effective for the treatment of small-intestinal bacterial overgrowth?