Antibiotic Treatment of Constipation-Predominant Irritable Bowel Syndrome

Background

The antibiotic rifaximin is used to treat non-constipated irritable bowel syndrome (IBS). Methane production is associated with constipation and its severity in constipation-predominant IBS (C-IBS). A previous retrospective study suggested that rifaximin and neomycin was superior to neomycin alone in improving symptoms in methane-positive subjects.

Aims

To determine the effectiveness of neomycin alone or with rifaximin in improving symptoms in methane-positive C-IBS subjects.

Methods

A double-blind, randomized, placebo-controlled trial was performed from 2010 to 2013 at three tertiary care centers. Subjects aged 18–65 with C-IBS (Rome II criteria) and breath methane (>3 ppm) meeting the inclusion and exclusion criteria were recruited. Subjects completed a baseline symptom questionnaire rating the severity of abdominal and bowel symptoms on a visual analog scale and were randomized to receive neomycin and placebo or neomycin and rifaximin for 14 days. Symptom severity was assessed by weekly questionnaire for 2 weeks of therapy and 4 additional weeks of follow-up.

Results

Thirty-one subjects (16 neomycin and placebo, 15 neomycin and rifaximin) were included in the intention-to-treat analysis. Constipation severity was significantly lower in the neomycin and rifaximin group (28.6 ± 30.8) compared to neomycin alone (61.2 ± 24.1) (P = 0.0042), with greater improvement in constipation (P = 0.007), straining (P = 0.017) and bloating (P = 0.020), but not abdominal pain. In the neomycin and rifaximin group, subjects with methane <3 ppm after treatment reported significantly lower constipation severity (30.5 ± 21.8) than subjects with persistent methane (67.2 ± 32.1) (P = 0.020).

Conclusions

Rifaximin plus neomycin is superior to neomycin alone in improving multiple C-IBS symptoms. This effect is predicted by a reduction in breath methane.     

Rifaximin is associated with modest,transient decreases in multiple taxa in the gut microbiota of patients with diarrhoea-predominant irritable bowel syndrome

Rifaximin, a non-systemic antibiotic, is efficacious for the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D). Given the emerging association between the gut microbiota and IBS, this study examined potential effects of rifaximin on the gastrointestinal microbial community in patients with IBS-D. TARGET 3 was a randomised, double-blind, placebo-controlled, phase 3 study. Patients with IBS-D initially received open-label rifaximin 550 mg 3 times daily (TID) for 2 weeks. Patients who responded to the initial treatment and then relapsed were randomised to receive 2 repeat courses of rifaximin 550 mg TID or placebo for 2 weeks, with each course separated by 10 weeks. Stool samples were collected at the beginning and end of open-label treatment, at the beginning and end of the first double-blind treatment, and at the end of the study. As a secondary analysis to the TARGET 3 trial, the composition and diversity of the gut microbiota were assessed, from a random subset of patients, using variable 4 hypervariable region 16S ribosomal RNA gene sequencing. Samples from 103 patients were included. After open-label rifaximin treatment for 2 weeks, 7 taxa (e.g. Peptostreptococcaceae, Verrucomicrobiaceae, Enterobacteriaceae) had significantly lower relative abundance at a 10% false discovery rate threshold. The effects of rifaximin were generally short-term, as there was little evidence of significantly different changes in taxa relative abundance at the end of the study (up to 46 weeks) versus baseline. The results suggest that rifaximin has a modest, largely transient effect across a broad range of stool microbes. Future research may determine whether the taxa affected by rifaximin are causally linked to IBS-D.

ClinicalTrials.gov identifier number: NCT01543178.     

Current gut-directed therapies for irritable bowel syndrome

Opinion statement Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that can present with a wide array of symptoms that make treatment difficult. Current therapies are directed at relieving symptoms of abdominal pain or discomfort, bloating, constipation, and diarrhea. Pharmacologic agents used to treat IBS-associated pain include myorelaxants, peppermint oil, and peripherally acting opiates. Dicyclomine and hyoscyamine, the two myorelaxants available in the United States, have not been proven effective in reducing abdominal pain in patients with IBS. The efficacy of peppermint oil is debated, but methodological problems with existing studies preclude definitive judgment. Loperamide is ineffective for relief of abdominal pain. For IBS patients with excessive abdominal bloating, a small number of studies suggest that bacterial eradication with gut-directed antibiotics and bacterial reconstitution with nonpathogenic probiotics may reduce flatulence. For constipation-predominant (C-IBS) symptoms, current treatment options include fiber supplementation, polyethylene glycol, and tegaserod. Soluble fibers (ispaghula, calcium polycarbophil, psyllium) are more effective than insoluble fibers (wheat bran, corn fiber) in alleviating global symptoms and relieving constipation, although fiber in general has marginal benefit in treatment of overall IBS symptoms. Polyethylene glycol increases bowel frequency in chronic constipation, but its overall efficacy against IBS is unclear. Tegaserod, a 5-HT₄ agonist, demonstrates superiority over placebo in improving bowel frequency and stool consistency and alleviating abdominal pain and bloating in women with C-IBS. Overall global symptoms are modestly improved with tegaserod when compared with placebo. Additional agents under investigation for C-IBS include the ClC₂ chloride channel opener lubiprostone, μ-opioid receptor antagonist alvimopan, and 5-HT₄ agonist renzapride. For diarrhea-predominant (D-IBS) symptoms, available therapies include loperamide, alosetron, and clonidine. Alosetron, a 5-HT₃ antagonist, is superior to placebo for reducing bowel frequency, improving stool consistency, and relieving abdominal pain in women with D-IBS. However, alosetron is available under a restricted license because of concerns for ischemic colitis and severe constipation necessitating colectomy. Clonidine may be helpful in alleviating global symptoms for D-IBS patients.     

A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation

BACKGROUND: It has been proposed that treatments for irritable bowel syndrome with constipation (IBS-C) should provide rapid symptomatic relief, be intermittent, and effective upon repeated use. AIMS: To evaluate the efficacy and safety of tegaserod on IBS symptoms, and its impact on quality of life and health economic measures. PATIENTS: Women (> or = 18 years of age) with IBS-C according to the Rome II criteria. METHODS: Prospective, double blind, placebo controlled, randomised trial. Women with IBS-C either received tegaserod 6 mg twice daily or placebo for one month. Patients with at least a partial response entered a treatment free interval. Upon symptom recurrence, tegaserod treated patients were re-randomised to tegaserod or placebo for an additional month. Primary efficacy variables were response (overall IBS symptoms and abdominal discomfort/pain) to first and repeated treatment. Analysis was by intention to treat. RESULTS: 2660 patients and 1191 patients were randomised for first and repeated treatment respectively. Tegaserod was superior to placebo for each primary efficacy variable (first treatment: 33.7% v 24.2% responders respectively for relief of IBS symptoms and 31.3% v 22.1% for relief of abdominal discomfort/pain; repeated treatment: 44.9% v 28.7%, and 42.4% v 27.1%, all p < 0.0001). Tegaserod was superior to placebo for every secondary efficacy variable (relief of abdominal discomfort/pain, bloating and constipation; stool frequency and consistency). A response to tegaserod was observed within the first treatment week. Tegaserod produced greater satisfaction, work productivity, and improved quality of life than placebo (p < 0.05). CONCLUSION: Tegaserod provides rapid and sustained relief of IBS-C symptoms both during first and repeated treatment.     

An Asia-Pacific,double blind,placebo controlled,randomised study to evaluate the efficacy,safety, and tolerability of tegaserod in patients with irritable bowel syndrome

BACKGROUND: Tegaserod has been shown to be an effective therapy for the multiple symptoms of irritable bowel syndrome (IBS) in Western populations. However, little information is available regarding the use of tegaserod in the Asia-Pacific population. AIMS: To evaluate the efficacy, safety, and tolerability of tegaserod versus placebo in patients with IBS from the Asia-Pacific region. PATIENTS: A total of 520 patients from the Asia-Pacific region with IBS, excluding those with diarrhoea predominant IBS. METHODS: Patients were randomised to receive either tegaserod 6 mg twice daily (n=259) or placebo (n=261) for a 12 week treatment period. The primary efficacy variable (over weeks 1-4) was the response to the question: "Over the past week do you consider that you have had satisfactory relief from your IBS symptoms?" Secondary efficacy variables assessed overall satisfactory relief over 12 weeks and individual symptoms of IBS. RESULTS: The mean proportion of patients with overall satisfactory relief was greater in the tegaserod group than in the placebo group over weeks 1-4 (56% v 35%, respectively; p<0.0001) and weeks 1-12 (62% v 44%, respectively; p<0.0001). A clinically relevant effect was observed as early as week 1 and was maintained throughout the treatment period. Reductions in the number of days with at least moderate abdominal pain/discomfort, bloating, no bowel movements, and hard/lumpy stools were greater in the tegaserod group compared with the placebo group. Headache was the most commonly reported adverse event (12.0% tegaserod v 11.1% placebo). Diarrhoea led to discontinuation in 2.3% of tegaserod patients. Serious adverse events were infrequent (1.5% tegaserod v 3.4% placebo). CONCLUSIONS: Tegaserod 6 mg twice daily is an effective, safe, and well tolerated treatment for patients in the Asia-Pacific region suffering from IBS and whose main bowel symptom is not diarrhoea.     

替加色罗治疗肠易激综合征的系统评价

目的 评价替加色罗治疗肠易激综合征(irritable bowel syndrome,IBS)的有效性和安全性.方法 对替加色罗治疗便秘型或非腹泻型IBS的随机对照试验(RCTs)进行系统评价.结果 共纳入13项RCTs,7 189例患者.替加色罗12 mg/d和4 mg/d对总体IBS症状的改善均优于安慰剂;对腹痛/腹部不适症状的缓解与安慰剂比无显著差异;对腹胀的疗效,各研究结果不一致;腹泻发生率显著高于安慰剂,替加色罗组报道了2例缺血性心脏病,严重不良事件的发生率与安慰剂比无显著差异.结论 替加色罗能改善便秘型或非腹泻型IBS患者的总体症状;缓解腹痛/腹部不适和腹胀等症状的证据不足;腹泻是替加色罗的主要不良反应.     

Symptom patterns and relative distribution of functional bowel disorders in 1,023 gastroenterology patients in Iran

Background and aims There are scanty data on functional bowel disorder (FBD) patterns in Iran. This first-time study tried to provide preliminary data on relative distribution of different types of FBD and their symptom patterns in Iranian patients.Methods A consecutive sample of 1,023 patients in an outpatient gastroenterology clinic in central Tehran was interviewed using two questionnaires based on Rome II criteria from December 2004 to May 2005 to detect FBD patients.Results Of 1,023 gastroenterology patients, 410 met Rome II criteria for FBD; functional constipation, 115 (28%); irritable bowel syndrome (IBS), 110 (27%) [IBS-C, 29%; IBS-D, 11%; IBS-A, 60%]; functional bloating, 102 (25%); unspecified FBD, 76 (18%); and functional diarrhea, 7 (2%). FBD had no association with age or level of education, while it was more frequent in women (P=0.001). FBD was also more frequent among those with a history of abdominal/pelvic surgery (P=0.021). IBS patients had a lower mean of age compared with non-FBD group, while patients with constipation were older (Mann–Whitney U test, P=0.006). Constipation-related symptoms were the most frequent symptoms among IBS patients. Constipation (<3 defecations/week) was also the most frequent change in bowel habit in bloating and unspecified FBD patients. Fourteen percent of IBS consulters and 8.7% of functional constipation consulters met Rome II criteria for dyspepsia (disregarding the ruling out of upper gastrointestinal organic disease). Only 20% of patients with functional constipation were consulters.Conclusions Population-based studies at provincial levels are essential to clarify FBD patterns in each provincial district in the country.     

Development of Functional Diarrhea,Constipation, Irritable Bowel Syndrome,and Dyspepsia During and After Traveling Outside the USA

Background Persistent gastrointestinal (GI) symptoms after travel abroad may be common. It remains unclear how often subjects who developed new GI symptoms while abroad have persistent symptoms on return. The objective of this retrospective study was to evaluate the prevalence of persistent GI symptoms in a healthy cohort of travelers. Methods One hundred and eight consecutive patients, mostly returned missionaries, attending the University of Utah International Travel Clinic for any reason (but mostly GI symptoms) had data recorded about their bowel habits before, during, and after travel abroad. All subjects had standard hematological, biochemical, and microbiological tests to exclude known causes of their symptoms. Endoscopic procedures were performed when considered necessary by the treating physician. Diarrhea, constipation, irritable bowel syndrome (IBS), bloating, and dyspepsia were defined according to the Rome II Criteria. Results Eighty three (82% men and 18% women, median age 21 years) completed the survey with 68 subjects completing the questionnaire about bowel habits before and during travel. Among the respondents, 55 (82.1%) did not have any symptoms before travel. During travel, 41 (63%) developed new onset diarrhea; 6 (9%) developed constipation; 16 (24%) IBS, 29 (45%) bloating; and 11 (16%) dyspepsia. Of those who developed symptoms during travel, 27 (68%) had persistent diarrhea, 3 (50%) had persistent constipation, 10 (63%) had persistent IBS, 12 (43%) had persistent bloating and 8 (73%) had persistent dyspepsia. The presence of bowel symptoms during and after travel was not associated with age, gender, travel destination, or duration of travel. Conclusions: This study suggests that new onset of diarrhea, IBS, constipation, and dyspepsia are common among subjects traveling abroad. Gastrointestinal symptoms that develop during travel abroad usually persist on return. Institution where work was performed: Department of Medicine, University of Utah, Salt Lake City, Utah, USA An erratum to this article can be found at     

Germs, gas and the gut; the evolving role of the enteric flora in IBS

Gas-related symptoms are common in irritable bowel syndrome (IBS), though their pathophysiology remains poorly understood, various studies invoking increased gas production, impaired gas transit, and increased sensitivity to gas. Recent evidence suggests a potential role for bacterial overgrowth in some patients with IBS; the study discussed herein provides further support for this concept by describing an amelioration of bloating and flatulence following a short course of the poorly absorbed antibiotic, rifaximin.     

Abnormalities of GI transit in bloated irritable bowel syndrome: effect of bran on transit and symptoms

OBJECTIVES: Bloating is an important but poorly understood symptom in irritable bowel syndrome (IBS) that is often aggravated by bran. The aim of our study was to determine whether IBS patients with bloating responded to bran differently from healthy controls. METHODS: A total of 12 patients with IBS (according to Rome I criteria), all with moderate to severe bloating, and 12 healthy controls participated in a two way, double blind, randomized, cross-over trial of bran versus placebo (crushed biscuits) 15 g b.i.d. An average daily pain index and bloating score were derived from daily symptom diaries. On day 14, gastric emptying, small bowel transit, percent remaining in ascending colon, and geometric center of a meal marker at 24 h were calculated from scintigraphic images obtained after ingesting a Tc99m-labeled rice pudding meal with 15 g of either placebo or coarse bran. RESULTS: Results are given as median (range). Bran significantly increased the pain index and bloating (p < 0.02) in IBS patients but not controls. The most striking finding was that the small bowel transit time of the meal without bran was markedly faster in IBS patients than in controls, being 203 min (range 109-313) versus 367 min (219-543), p < 0.001. Although in controls bran accelerated small bowel transit time to 262 min (180-380), p = 0.03, and significantly reduced % remaining in the ascending colon from 22% (0-46) to 3% (0-25), p = 0.03, this was not seen in the IBS patients. Bran accelerated whole gut transit as assessed by geometric center at 24 h in both IBS patients and controls. CONCLUSIONS: Bran accelerates small bowel transit and ascending colon clearance without causing symptoms in controls. Small bowel transit is rapid in IBS patients with bloating and, unlike in healthy control subjects, cannot be further accelerated by bran, which nevertheless aggravates symptoms of pain and bloating. We speculate that bran-induced bloating may originate in the colon rather than the small bowel.     

Does rifaximin offer any promise in Crohn's disease in remission and concurrent irritable bowel syndrome-like symptoms?

Microbiota plays an important role in many diseases including inflammatory bowel diseases. Inflammatory bowel disease patients can have concurrent irritable bowel syndrome symptoms similar to those associated with a flare. The potential role of gut dysbiosis in the pathogenesis of inflammatory bowel disease provides a rationale for treating such patients with rifaximin. This study aimed to assess the efficacy of rifaximin in the management of irritable bowel syndrome-like symptoms (bloating, abdominal pain, stool consistency) and quality of life in patients with Crohn''s disease in remission.The present study included 86 patients with Crohn''s disease in remission (fecal calprotectin <50 μg/g, C-reactive protein <0.5 mg/dL, simple endoscopic score for Crohn''s disease <2) and associated irritable bowel syndrome-like symptoms (bloating, abdominal pain, diarrhea). These patients were randomly assigned to rifaximin treatment group (44 patients) and the control group (42 patients). Besides the baseline inflammatory bowel disease treatment and antispasmodics (as needed), patients in the rifaximin treatment group received 3 repeated courses of treatment, each course being represented by 1200 mg/d of rifaximin for 10 days and 20 days free of treatment (3 months consecutively); patients in the control group also received antispamodics as needed and were observed for 3 months.Monthly analyses of bloating score, abdominal pain score, stool consistency score, and quality of life score showed significant improvement after treatment in the rifaximin group in contrast with control group. Significantly more patients in the rifaximin group than in the control group met the criteria for adequate improvement of bloating score after 3 months of treatment (59.09% vs 19.04%, P = .01), adequate improvement of abdominal pain score (54.5% vs 21.4%, P = .04), stool consistency score (34.09% vs 14.2%, P = .03), and quality of life score (70.4% vs 21.4%, P < .001).Rifaximin in a dose of 1200 mg/d, 10 d/mo, 3 months consecutively is an effective medication for concurrent irritable bowel syndrome-like symptoms in patients with Crohn''s disease in remission.     

Identification of Patients with Non-D,Non-C Irritable Bowel Syndrome and Treatment with Renzapride: An Exploratory,Multicenter, Randomized,Double-Blind,Placebo-Controlled Clinical Trial

This was an exploratory study of renzapride in 168 male and female patients with non-D, non-C irritable bowel syndrome (IBS). Patients were randomized to placebo or renzapride (1, 2, or 4 mg/day) for 8 weeks. The primary efficacy variable was patient-reported satisfactory relief of IBS symptoms. Secondary variables included relief of abdominal pain/discomfort. The proportion of patients reporting satisfactory relief of their IBS symptoms for at least 50% of the time did not differ significantly from those on placebo. However, post hoc analysis in women showed differences in responder rate on renzapride versus placebo of 18.2% (95% CI −5% to 42%; P = 0.066) during weeks 1–4 and 6% (95% CI −21% to 33%; P = 0.339) during weeks 5–8. Renzapride was well tolerated and most adverse events were mild to moderate in intensity. Further studies are warranted to determine whether renzapride is beneficial in this patient population.     

Rifaximin,gut microbes and mucosal inflammation: unraveling a complex relationship

Rifaximin is a non-systemic, broad-spectrum antibiotic that acts against gram-positive, gram-negative, and anaerobic bacteria. Clinical studies indicate that rifaximin is beneficial in treating irritable bowel syndrome (IBS). The mechanism responsible for the beneficial effects of rifaximin is not clear. In a recent study, we reported that rifaximin alters the bacterial population in the ileum of rats, leading to a relative abundance of Lactobacillus species. These changes prevent gut inflammation and visceral hyperalgesia caused by chronic stress. To more closely mirror human clinical studies in which rifaximin is used to treat IBS symptoms, we performed additional studies and showed that rifaximin reversed mucosal inflammation and barrier dysfunction evoked by chronic stress. These beneficial effects were accompanied by a striking increase in the abundance of Lactobacillaceae and a marked reduction in the number of segmented filamentous bacteria after rifaximin treatment. These microbial changes may contribute to the antiinflammatory effects of rifaximin on the intestinal mucosa.     

Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome – a pilot study

Abstract

Objective. Post-infective irritable bowel syndrome (PI-IBS) is characterized by continuing symptoms of irritable bowel syndrome, typically diarrhea-predominant, following an episode of acute gastroenteritis. There is often an increase in sub-epithelial inflammatory and neuroendocrine cells on colonic mucosal biopsy. Mesalamine is an anti-inflammatory agent, effective in the treatment of inflammatory bowel disease. The goal of this study was to compare mesalamine to placebo on symptoms and quality-of-life (QOL) in PI-IBS. Material and methods. Twenty patients who developed diarrhea-predominant IBS after gastroenteritis were randomized to receive mesalamine (Asacol®) 1.6 gm b.i.d. or placebo for 12 weeks in a double-blind placebo-controlled study. QOL was assessed using the IBS-QOL questionnaire. Stool frequency, stool consistency, urgency, severity of abdominal pain, severity of bloating, and global-improvement scale were recorded in daily diaries for 7 days at baseline and every 4 weeks. Data were analyzed by comparing the change from baseline to last follow-up. Results. One patient withdrew after randomization; data were incomplete in two patients. Thus, data were analyzed from 17 patients (11 men and 6 women, median age: 27 years, range 22–45 years). Mesalamine was not associated with significant improvement in global symptoms, abdominal pain, bloating, stool urgency, frequency, or consistency (all p ≥ 0.11) or QOL (p ≥ 0.16). Conclusions. There was no significant improvement in global symptoms or overall QOL with mesalamine in patients with PI-IBS.     

The Efficacy of an Herbal Medicine, Carmint, on the Relief of Abdominal Pain and Bloating in Patients with Irritable Bowel Syndrome: A Pilot Study

Carmint contains total extracts of Melissa officinalis, Mentha spicata, and Coriandrum sativum, which have antispasmodic, carminative, and sedative effects. As abdominal pain/discomfort and bloating are commonly observed in patients with irritable bowel syndrome, we decided to evaluate the effectiveness of Carmint in relieving these symptoms in irritable bowel syndrome patients. We randomly assigned 32 irritable bowel syndrome patients to receive either Carmint or placebo, plus Loperamide or psyllium (based on their predominant bowel function), for 8 weeks. T-test analysis of the results showed that the severity and frequency of abdominal pain/discomfort were significantly lower in the Carmint group than the placebo group at the end of the treatment (P=0.016 and P=0.001, respectively), as were the severity and frequency of bloating (P=0.02 and P=0.002, respectively). This pilot study suggests that Carmint plus loperamide or Carmint plus psyllium (depending on the irritable bowel syndrome subtype) might be effective in these patients.     

Daily gastrointestinal symptoms in women with and without a diagnosis of IBS

This study compared daily gastrointestinal symptoms and stool characteristics across two menstrual cycles, and recalled bowel symptoms and psychological distress in women with irritable bowel syndrome (IBS,N=22), IBS nonpatients (IBS-NP,N=22), and controls (N =25). Daily reports of abdominal pain, bloating, intestinal gas, constipation, and diarrhea did not differ significantly between the IBS and IBS-NP groups but both groups reported significantly higher symptoms than the control group. Stool consistencies was significantly looser in the IBS group relative to the control group. Menstrual cycle effects on symptoms were noted in all the groups. There were no significant differences in psychological distress between women with IBS, and IBS-NP, but both groups reported significantly higher global distress than the control group. The lack of difference between the IBS and IBS-NP groups in contrast to the results of others, can be understood in terms of differences in recruitment strategies.This work was supported by the National Institute for Nursing Research, NIH, grant NR01094.     

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence

AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence. METHODS: Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H2-breath test (LHBT) was performed at baseline and end of study. RESULTS: One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3% vs 22.9%, p = 0.03). This improvement was maintained at the end of phase 3 (28.6% vs 11.5%, p = 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p < 0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5% vs 18.2%; p = 0.04) persisting by the end of phase 3 (27% vs 9.1%; p = 0.05). H2-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p = 0.01). No adverse events were reported. CONCLUSIONS: Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H2-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.     

Single‐blind follow‐up study on the effectiveness of a symbiotic preparation in irritable bowel syndrome

OBJECTIVE: Experimental and clinical studies have shown that a novel symbiotic (known as SCM‐III) exerts a beneficial effect on gut translocation and local and systemic inflammatory and microbial metabolic parameters. The present investigation was a preliminary trial on the effectiveness of SCM‐III for irritable bowel syndrome (IBS). METHODS: Sixty‐eight consecutive adult patients with IBS who were free from lactose malabsorption, abdominal surgery, overt psychiatric disorders and ongoing psychotropic drug therapy or ethanol abuse were studied prospectively and divided into 2 groups that were comparable for age, gender, body size, education and pattern of presenting symptoms. The 2 groups were blindly given for 12 weeks either SCM‐III 10 mL t.i.d or the same dosage of heat‐inactivated symbiotic. RESULTS: Treatment with SCM‐III was ‘effective’ or ‘very effective’ in more than 80% of the patients (P < 0.01 vs baseline values and control). Less than 5% reported ‘not effective’ as the final evaluation compared with over 40% of patients in the control group. After 6 weeks of treatment, a significant improvement of pain and bloating was reported in the treatment group compared with control and baseline values. There was also a benefit for bowel habits, mostly for patients with constipation or alternating bowel habits. No overt clinical or biochemical adverse side‐effects were recorded. CONCLUSION: Compared with baseline values and the control group, SCM‐III resulted in a significant increase in lactobacilla, eubacteria and bifidobacteria, which suggests that some selected IBS patients could benefit substantially from symbiotics, but the treatment may need to be given on a cyclic schedule because of the temporary modification of the fecal flora.     

Irritable bowel syndrome and bloating

Gaseous symptoms in irritable bowel syndrome (IBS) including eructation, flatulence, and bloating occur as a consequence of excess gas production, altered gas transit, abnormal perception of normal amounts of gas within the gastrointestinal tract, or dysfunctional somatic muscle activity in the abdominal wall. Because of the prominence of gaseous complaints in IBS, recent investigations have focussed on new insights into pathogenesis and novel therapies of bloating. The evaluation of the IBS patient with unexplained gas and bloating relies on careful exclusion of organic disease with further characterisation of the underlying condition with directed functional testing. Treatment of gaseous symptomatology in IBS should be targeted to pathophysiologic defects whenever possible. Available therapies include lifestyle alterations, dietary modifications, enzyme preparations, adsorbents and agents which reduce surface tension, treatments that alter gut flora, and drugs that modulate gut transit.     

A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS

BACKGROUND: A randomized, double blind, placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Six hundred and sixty-two men were randomized to treatment with alosetron 0.5, 1.0, 2.0, 4.0 mg, or placebo twice daily for 12 wk, followed by a 4-wk posttreatment period. Adequate relief of IBS pain and discomfort during week 5-12 of the treatment phase was the primary endpoint; secondary endpoints included bowel urgency, stool frequency, and consistency, incomplete evacuation, bloating, and abdominal pain or discomfort. RESULTS: Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms. The average rate of adequate relief during week 5-12 was significantly higher in the alosetron 1.0 mg twice-daily group compared to placebo (53%vs 40%, p= 0.04), and all doses of alosetron significantly reduced stool consistency scores (p < 0.001) indicating firmer stools. No significant effects of alosetron were seen with regard to urgency, number of bowel movements, bloating, and incomplete evacuation. Constipation was the most common adverse event and occurred in a dose-related manner among subjects receiving alosetron, 9% (0.5 mg twice daily), 15% (1.0 mg twice daily), 11% (2.0 mg twice daily), and 21% (4.0 mg twice daily). No serious adverse events of constipation were reported. One subject in the 0.5 mg twice-daily group had an episode of rectal bleeding suggestive of a possible diagnosis of ischemic colitis. CONCLUSIONS: Alosetron 1 mg twice daily provided adequate relief of IBS pain and discomfort, and improved stool consistency in men with diarrhea-predominant IBS.