Rifaximin Treatment for Irritable Bowel Syndrome
Rifaximin Treatment for Irritable Bowel Syndrome
Background While rifaximin was able to improve symptoms in patients with irritable bowel syndrome (IBS) in phase III trials, these results are yet to be repeated in phase IV studies.
Aim To evaluate the treatment response to rifaximin in IBS patients in a phase IV trial.
Methods IBS patients underwent lactulose hydrogen breath testing (LHBT). LHBT-positive patients were treated with rifaximin for 14 days. Prior to treatment as well as at week 4 and 14 following the start of rifaximin treatment, patients completed a questionnaire assessing symptom severity on a Likert scale from 0 to 10.
Results One hundred and six of 150 IBS patients (71%) were LHBT-positive and treated with rifaximin. As assessed at week 4 following commencement of the therapy, rifaximin provided significant improvement of the following IBS-associated symptoms: bloating (5.5±2.6 before the start of the treatment vs. 3.6±2.7 at week 4, P<0.001), flatulence (5.0±2.7 vs. 4.0±2.7, P=0.015), diarrhoea (2.9±2.4 vs. 2.0±2.4, P=0.005) and abdominal pain (4.8±2.7 vs. 3.3±2.5, P<0.001). Overall well-being also significantly improved (3.9 ± 2.4 vs. 2.7 ± 2.3, P < 0.001). Similar improvements in IBS symptoms were obtained at week 14. Eighty-six per cent of patients undergoing repetitive LHBT (55/64) tested negative at week 4.
Conclusions We found a high percentage of LHBT-positive IBS patients. IBS-associated symptoms (bloating, flatulence, diarrhoea, pain) were improved for a period of 3 months following 2 weeks of treatment with rifaximin. We conclude that rifaximin treatment alleviates symptoms in LHBT-positive IBS patients.
Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition of unknown aetiology and is characterised by the presence of abdominal pain and altered bowel function in the absence of clinical 'alarm' signs, such as anaemia or significant weight loss. Currently, more than 10% of the general population suffers from IBS, leading to considerable healthcare expenditures. The exact pathophysiology of IBS remains unknown; both central and peripheral mechanisms have been implicated in IBS pathogenesis. IBS patients may present with alterations in their intestinal microbiota and they are tested significantly more frequently positive by lactulose hydrogen breath test (LHBT) when compared to healthy controls. The reported prevalence of the positive LHBT in IBS patients ranges from 14% to 78%. Authors of a systematic review and meta-analysis have calculated that a pooled prevalence of a positive LHBT or glucose hydrogen test is 54% (95% CI: 32–76%) or 31% (95% CI: 14–50%) respectively. The pooled odds ratio for any positive hydrogen test in IBS patients compared to healthy subjects was 3.45 (95% CI: 0.9–12.7) or 4.7 (95% CI: 1.7–12.95), depending on the criteria used for defining a positive readout of a test.
The LHBT is one of the most commonly used breath tests that is based on measurement of hydrogen concentration in breath samples every 15 min (for up to 3 h) following the ingestion of 10 g of the non-absorbable sugar lactulose dissolved in water. According to the original definition of the positive LHBT, the rise of >20 ppm in hydrogen concentration occurring at least 15 min before a second rise in hydrogen concentration is believed to be indicative, among other phenomena, of rapid small bowel transit and/or small intestinal bacterial overgrowth (SIBO). A recent meta-analysis concluded that the breath test findings in IBS appear to be valid for SIBO diagnosis. However, the appropriateness of use of hydrogen breath testing in IBS as well as the choice of substrate that provides the best test characteristics is a subject of some controversy. In addition, it is also debated whether carbohydrate breath testing is an appropriate surrogate for diagnosing SIBO in IBS patients. SIBO has been conventionally diagnosed using jejunal fluid culture; the cultures are considered positive for SIBO if the total bacterial count is ≥10 colony forming units (CFU) of coliform bacteria per ml of jejunal fluid aspirate. The results of the early studies, where sampling of the small intestinal luminal contents was performed using an aseptic technique demonstrated an LHBT sensitivity and specificity of 68% and 44% and 16.7% and 70%, arguing that breath- hydrogen testing may not be entirely adequate for SIBO diagnosis. However, difficulties in aspiration of jejunal fluid, potential for contamination during sampling, and the possibility of false negative results, especially when culturing for obligate anaerobes, are important limitations of this methodology. Therefore, many view indirect tests, such as breath tests, as a better alternative to this laborious method.
The use of systemic antibiotics for treatment of IBS has been reported with mixed results. Rifaximin is a semisynthetic derivative of rifamycin, which contains an additional benzimidazole ring that prevents rifaximin from being absorbed systemically (absorption 0.4% after oral administration).In vitro, rifaximin demonstrates activity against Gram-positive and Gram-negative, aerobic and anaerobic bacteria. This antibiotic has been approved by the Food and Drug Administration (FDA) for treating traveller's diarrhoea and minimal hepatic encephalopathy. Several trials have demonstrated efficacy of rifaximin for treatment of global symptoms and bloating in IBS. Validation of these findings in a phase IV trial is currently lacking. Therefore, we aimed to perform a study to assess the prevalence of positive LHBT and the treatment efficacy of rifaximin in a cohort of IBS patients in daily clinical practice.
Abstract and Introduction
Abstract
Background While rifaximin was able to improve symptoms in patients with irritable bowel syndrome (IBS) in phase III trials, these results are yet to be repeated in phase IV studies.
Aim To evaluate the treatment response to rifaximin in IBS patients in a phase IV trial.
Methods IBS patients underwent lactulose hydrogen breath testing (LHBT). LHBT-positive patients were treated with rifaximin for 14 days. Prior to treatment as well as at week 4 and 14 following the start of rifaximin treatment, patients completed a questionnaire assessing symptom severity on a Likert scale from 0 to 10.
Results One hundred and six of 150 IBS patients (71%) were LHBT-positive and treated with rifaximin. As assessed at week 4 following commencement of the therapy, rifaximin provided significant improvement of the following IBS-associated symptoms: bloating (5.5±2.6 before the start of the treatment vs. 3.6±2.7 at week 4, P<0.001), flatulence (5.0±2.7 vs. 4.0±2.7, P=0.015), diarrhoea (2.9±2.4 vs. 2.0±2.4, P=0.005) and abdominal pain (4.8±2.7 vs. 3.3±2.5, P<0.001). Overall well-being also significantly improved (3.9 ± 2.4 vs. 2.7 ± 2.3, P < 0.001). Similar improvements in IBS symptoms were obtained at week 14. Eighty-six per cent of patients undergoing repetitive LHBT (55/64) tested negative at week 4.
Conclusions We found a high percentage of LHBT-positive IBS patients. IBS-associated symptoms (bloating, flatulence, diarrhoea, pain) were improved for a period of 3 months following 2 weeks of treatment with rifaximin. We conclude that rifaximin treatment alleviates symptoms in LHBT-positive IBS patients.
Introduction
Irritable bowel syndrome (IBS) is a chronic gastrointestinal condition of unknown aetiology and is characterised by the presence of abdominal pain and altered bowel function in the absence of clinical 'alarm' signs, such as anaemia or significant weight loss. Currently, more than 10% of the general population suffers from IBS, leading to considerable healthcare expenditures. The exact pathophysiology of IBS remains unknown; both central and peripheral mechanisms have been implicated in IBS pathogenesis. IBS patients may present with alterations in their intestinal microbiota and they are tested significantly more frequently positive by lactulose hydrogen breath test (LHBT) when compared to healthy controls. The reported prevalence of the positive LHBT in IBS patients ranges from 14% to 78%. Authors of a systematic review and meta-analysis have calculated that a pooled prevalence of a positive LHBT or glucose hydrogen test is 54% (95% CI: 32–76%) or 31% (95% CI: 14–50%) respectively. The pooled odds ratio for any positive hydrogen test in IBS patients compared to healthy subjects was 3.45 (95% CI: 0.9–12.7) or 4.7 (95% CI: 1.7–12.95), depending on the criteria used for defining a positive readout of a test.
The LHBT is one of the most commonly used breath tests that is based on measurement of hydrogen concentration in breath samples every 15 min (for up to 3 h) following the ingestion of 10 g of the non-absorbable sugar lactulose dissolved in water. According to the original definition of the positive LHBT, the rise of >20 ppm in hydrogen concentration occurring at least 15 min before a second rise in hydrogen concentration is believed to be indicative, among other phenomena, of rapid small bowel transit and/or small intestinal bacterial overgrowth (SIBO). A recent meta-analysis concluded that the breath test findings in IBS appear to be valid for SIBO diagnosis. However, the appropriateness of use of hydrogen breath testing in IBS as well as the choice of substrate that provides the best test characteristics is a subject of some controversy. In addition, it is also debated whether carbohydrate breath testing is an appropriate surrogate for diagnosing SIBO in IBS patients. SIBO has been conventionally diagnosed using jejunal fluid culture; the cultures are considered positive for SIBO if the total bacterial count is ≥10 colony forming units (CFU) of coliform bacteria per ml of jejunal fluid aspirate. The results of the early studies, where sampling of the small intestinal luminal contents was performed using an aseptic technique demonstrated an LHBT sensitivity and specificity of 68% and 44% and 16.7% and 70%, arguing that breath- hydrogen testing may not be entirely adequate for SIBO diagnosis. However, difficulties in aspiration of jejunal fluid, potential for contamination during sampling, and the possibility of false negative results, especially when culturing for obligate anaerobes, are important limitations of this methodology. Therefore, many view indirect tests, such as breath tests, as a better alternative to this laborious method.
The use of systemic antibiotics for treatment of IBS has been reported with mixed results. Rifaximin is a semisynthetic derivative of rifamycin, which contains an additional benzimidazole ring that prevents rifaximin from being absorbed systemically (absorption 0.4% after oral administration).In vitro, rifaximin demonstrates activity against Gram-positive and Gram-negative, aerobic and anaerobic bacteria. This antibiotic has been approved by the Food and Drug Administration (FDA) for treating traveller's diarrhoea and minimal hepatic encephalopathy. Several trials have demonstrated efficacy of rifaximin for treatment of global symptoms and bloating in IBS. Validation of these findings in a phase IV trial is currently lacking. Therefore, we aimed to perform a study to assess the prevalence of positive LHBT and the treatment efficacy of rifaximin in a cohort of IBS patients in daily clinical practice.