Rifaximin for the treatment of irritable bowel syndrome – a drug safety evaluation

ABSTRACT

Introduction: Irritable bowel syndrome is a functional gastrointestinal disorder with a multifactorial etiology. Alterations of intestinal motility and immunity, gut-brain interactions, as well as gut microbiota dysbiosis contribute to the development of irritable bowel syndrome. Therefore, gut microbiota modulation by non-absorbable antibiotics is a therapeutic option in patients with IBS.

Areas covered: Published articles including patients with irritable bowel syndrome reporting data about rifaximin activity and safety have been searched throughout the literature and selected.

Expert opinion: The optimal antibiotic molecule should be local-acting, long-acting and safe-acting. Rifaximin is a non-absorbable antibiotic with additional anti-inflammatory and gut microbiota-modulating activity. It is effective in inducing symptoms relief in patients with IBS, even after repeated treatment courses. Rifaximin-related side effects in patients with IBS are reported to be mild and infrequent; microbial resistance is rare and transient, due to the high local concentration of the drug and to the absence of horizontal transmission. Clostridium difficile infection is not usual in patients receiving rifaximin in absence of predisposing conditions such as hospitalization and immunosuppression, which are uncommon in patients affected by irritable bowel syndrome. Nevertheless rifaximin is an antibiotic active against Clostridium difficile infection. Rifaximin has limited metabolic interactions and is not expected to interfere with drug metabolism in patients with normal hepatic function. These properties make rifaximin a safe antibiotic for gut microbiota modulation in patients with IBS.     

In vitro activity of rifaximin against isolates from patients with small intestinal bacterial overgrowth

Rifaximin, a non-absorbable rifamycin derivative, has published clinical efficacy in the alleviation of symptoms in patients with irritable bowel syndrome (IBS). Small intestinal bacterial overgrowth (SIBO) is associated with the pathogenesis of IBS. This study describes for the first time the antimicrobial effect of rifaximin against SIBO micro-organisms from humans. Fluid was aspirated from the third part of the duodenum from 567 consecutive patients; quantitative cultures diagnosed SIBO in 117 patients (20.6%). A total of 170 aerobic micro-organisms were isolated and the in vitro efficacy of rifaximin was studied by (i) minimum inhibitory concentration (MIC) testing by a microdilution technique and (ii) time–kill assays using bile to simulate the small intestinal environment. At a breakpoint of 32 μg/mL, rifaximin inhibited in vitro 85.4% of Escherichia coli, 43.6% of Klebsiella spp., 34.8% of Enterobacter spp., 54.5% of other Enterobacteriaceae spp., 82.6% of non-Enterobacteriaceae Gram-negative spp., 100% of Enterococcus faecalis, 100% of Enterococcus faecium and 100% of Staphylococcus aureus. For the time–kill assays, 11 E. coli, 15 non-E. coli Gram-negative enterobacteria and three E. faecalis isolates were studied. Rifaximin produced a >3 log₁₀ decrease in the starting inoculum against most of the tested isolates at 500 μg/mL after 24 h of growth. The results indicate that rifaximin has a potent effect on specific small bowel flora associated with SIBO. This conclusion should be regarded in light of the considerable time–kill effect at concentrations lower than those achieved in the bowel lumen after administration of conventional doses in humans.     

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

Aliment Pharmacol Ther 2010; 32: 1000–1006

Summary

Background 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. Aim To assess whether the combination of partially hydrolysed guar gum and rifaximin is more effective than rifaximin alone in the treatment of SIBO. Methods 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. Results 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). Conclusion The combination of rifaximin with partially hydrolysed guar gum seems to be more useful in eradicating SIBO compared with rifaximin alone.     

Rifaximin for the treatment of diarrhoea-predominant irritable bowel syndrome

Introduction: Rifaximin is a non-absorbable, semisynthetic antibiotic that acts as an inhibitor of bacterial RNA synthesis, with a broad spectrum of antibacterial activity. Due to its poor absorption, rifaximin has an increased exposure to the intestine, thus it is suitable for the treatment of many gastrointestinal (GI) diseases. In irritable bowel syndrome (IBS) pathogenesis, gut microbiota impairment may play a major role. The possibility of modulating intestinal bacteria using antibiotics, in particular, rifaximin, has been demonstrated to improve IBS symptoms in non-constipation subtypes of IBS.

Areas covered: We reviewed the use of rifaximin in diarrhoea-predominant IBS, focusing on its pharmacokinetic characteristics, its absorption in GI disease, its lack of interaction with other drugs and its new extended release formulation.

Expert opinion: Rifaximin, with its low systemic absorption and no clinically significant interactions with other drugs, may represent a treatment of choice for IBS, mainly due to its ability to act on IBS pathogenesis, through the modulation of gut microbiota. Further studies to analyse the effect of rifaximin treatment on the composition of faecal microbiota are warranted. In particular, they need to evaluate whether resistant bacterial strains are selected and whether they are still present in the faecal sample even a long time after therapy.     

Review article: rifaximin,a minimally absorbed oral antibacterial,for the treatment of travellers’ diarrhoea

Aliment Pharmacol Ther 31 , 1155–1164

Summary

Background Travellers’ diarrhoea, a common problem worldwide with significant medical impact, is generally treated with anti‐diarrhoeal agents and fluid replacement. Systemic antibiotics are also used in selected cases, but these may be associated with adverse effects, bacterial resistance and drug–drug interactions. Aim To review the clinical evidence supporting the efficacy and safety of the minimally absorbed oral antibiotic rifaximin in travellers' diarrhoea. Methods PubMed and the Cochrane Register of Controlled Clinical Trials (to January 2010) and International Society of Travel Medicine congress abstracts (2003–2009) were searched to identify relevant publications. Results A total of 10 publications were included in the analysis. When administered three times daily for 3 days, rifaximin is superior to placebo or loperamide; it is at least as effective as ciprofloxacin in reducing duration of illness and restoring wellbeing in patients with travellers' diarrhoea, both with and without identification of a pathogen, as well as in diarrhoea caused by Escherichia coli infection. Rifaximin demonstrates only minimal potential for development of bacterial resistance and for cytochrome P450‐mediated drug–drug interactions, and its tolerability profile is similar to that of placebo. Conclusion When antibiotic therapy is warranted in uncomplicated travellers' diarrhoea, rifaximin may be considered as a first‐line treatment option because of its favourable efficacy, tolerability and safety profiles.     

Rifaximin for the treatment of irritable bowel syndrome

INTRODUCTION: Few therapeutic options are available for irritable bowel syndrome (IBS). Lubiprostone is approved by the FDA for IBS with constipation, and alosetron in IBS with diarrhea (IBS-D). It has been proposed that alterations in the bowel microflora may play a role in the pathophysiology of IBS, and that modulation of the microflora holds therapeutic potential. Rifaximin is a nonsystemic antibiotic that has shown efficacy in IBS. AREAS COVERED: This narrative review covers the treatment options available for IBS-D and focuses on rifaximin. Rifaximin pharmacodynamics, clinical pharmacology and results of clinical studies from proof of concept to the latest Phase III and retreatment studies in IBS are summarized. Challenges to rifaximin use, safety issues and regulatory data are also discussed. EXPERT OPINION: The evidence supports rifaximin as an emerging treatment for IBS. Strategies for appropriate patient selection need to be further developed, and continued efficacy of rifaximin over repeated treatment courses needs to be better characterized.     

Update on the Management of Diarrhea‐Predominant Irritable Bowel Syndrome: Focus on Rifaximin and Eluxadoline

Diarrhea‐predominant irritable bowel syndrome (IBS‐D) is one of the most common diagnoses made by gastroenterologists. Current pharmacologic treatments for IBS‐D include fiber supplements, antidiarrheal over‐the‐counter medications, probiotics, antispasmodics, antidepressants, and a 5‐hydroxytryptophan 3 receptor antagonist. All of these options have limited efficacy in managing IBS‐D. Rifaximin, a nonabsorbable antibiotic, has been evaluated in patients with IBS‐D. In two randomized, double‐blind, placebo‐controlled phase III trials evaluating rifaximin 550 mg by mouth 3 times/day for 14 days, the primary efficacy end point was achieved by 9% more patients randomized to the rifaximin group compared with placebo (40.7% vs 31.7%, p<0.001, number needed to treat ~11). The primary efficacy end point was defined as the proportion of patients having adequate relief of global IBS symptoms for at least 2 of the 4 weeks during the primary follow‐up period (weeks 3–6). In the phase III trial examining the efficacy and safety of repeated courses of rifaximin in patients who responded to the initial 2‐week course, rifaximin given for up to two additional courses provided a statistically significant incremental benefit (33% vs 25%, p=0.02). Eluxadoline is a gut‐targeting μ and κ opioid receptor agonist and a δ opioid receptor antagonist. The dual mechanism of eluxadoline may explain the antidiarrheal and abdominal pain‐modulating properties and lack of profound constipation. In two identically designed randomized, double‐blind, placebo‐controlled phase III studies, 10.3% more patients in an eluxadoline 100 mg by mouth twice/day group met the primary efficacy end point during the follow‐up 1–12 week period compared with placebo (p<0.001). The primary efficacy end point was a composite response, defined as improvement in worst abdominal pain and stool consistency at the same time on most (50% or more) days during the follow‐up period. This review evaluates evidence for the use of rifaximin and eluxadoline in patients with IBS‐D. Rifaximin provides an additional modality for the management of IBS‐D patients; it has mild to moderate efficacy similar to other currently available treatment options. Rifaximin is relatively safe, lacks significant drug‐drug interactions, and can be used for up to two additional retreatment courses. This may make rifaximin a possible initial or second‐line treatment option. Eluxadoline can also offer relief to patients with IBS‐D. While effective, because of several limitations, including drug‐drug interactions and drug disease contraindications, as well as current lack of clinical experience, it may be tried as a second‐ or third‐line agent.     

Rifaximin for the treatment of irritable bowel syndrome

Introduction: Few therapeutic options are available for irritable bowel syndrome (IBS). Lubiprostone is approved by the FDA for IBS with constipation, and alosetron in IBS with diarrhea (IBS-D). It has been proposed that alterations in the bowel microflora may play a role in the pathophysiology of IBS, and that modulation of the microflora holds therapeutic potential. Rifaximin is a nonsystemic antibiotic that has shown efficacy in IBS.

Areas covered: This narrative review covers the treatment options available for IBS-D and focuses on rifaximin. Rifaximin pharmacodynamics, clinical pharmacology and results of clinical studies from proof of concept to the latest Phase III and retreatment studies in IBS are summarized. Challenges to rifaximin use, safety issues and regulatory data are also discussed.

Expert opinion: The evidence supports rifaximin as an emerging treatment for IBS. Strategies for appropriate patient selection need to be further developed, and continued efficacy of rifaximin over repeated treatment courses needs to be better characterized.     

利福昔明治疗感染性腹泻50例的随机双盲对照试验

目的 :评价利福昔明治疗感染性腹泻的疗效及安全性。方法 :采用随机、双盲对照临床试验设计 ,选用 18～ 6 5a病人共 12 6例 ,分为A ,B两组。分别用利福昔明与环丙沙星 2种药物治疗 ,用法一致 ,d 1,2粒 ,tid ,以后 2粒 ,bid ,疗程皆为 3～ 5d。结果 :利福昔明与环丙沙星临床疗效评价病例数分别为 5 0例和 5 7例 ,有效率分别为 94 %与 95 % ,细菌阳性率分别为 4 4%与 4 6 % ,细菌清除率分别为95 %与 92 % ,不良反应发生率分别为 2 %与 5 % (均P >0 .0 5 )。结论 :利福昔明是治疗成人肠道细菌感染的有效和安全的药物 ,与环丙沙星相当     

High dosage rifaximin for the treatment of small intestinal bacterial overgrowth

BACKGROUND: 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. AIMS: To assess efficacy, safety and tolerability of rifaximin 1600 mg with respect to 1200 mg/day for small intestinal bacterial overgrowth treatment. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Clinical predictors of small intestinal bacterial overgrowth by duodenal aspirate culture

Aliment Pharmacol Ther 2011; 33: 1059–1067

Summary

Background There has been increasing interest in small intestinal bacterial overgrowth (SIBO) after reports of a link with irritable bowel syndrome (IBS), yet our understanding of this entity is limited. Aim Our aim was to estimate the yield of patients undergoing duodenal aspirate culture, and to identify symptoms and features that predict SIBO. Methods A medical chart review of patients who had undergone duodenal aspirate culture at an academic medical centre in 2003 was performed to record clinical characteristics and culture results. The associations between aspirate results and symptoms, medical diagnoses and medication use were assessed using logistic regression. Results A total of 675 patients had available aspirate results. Mean age of the sample was 53 (s.d. 17) and 443 (66%) were female patients. Overall, 8% of aspirates were positive for SIBO; 2% of IBS patients had SIBO. Older age, steatorrhoea and narcotic use were associated with SIBO (P < 0.05). PPI use was not associated with SIBO, but was associated with bacterial growth not meeting criteria for SIBO (P < 0.05). Inflammatory bowel disease (IBD), small bowel diverticula and pancreatitis were positively associated with an abnormal duodenal aspirate (P < 0.05), but other conditions including IBS were not associated with SIBO. Conclusion Older age, steatorrhoea, narcotic use, IBD, small bowel diverticula and pancreatitis were associated with small intestinal bacterial overgrowth based on abnormal duodenal aspirate culture results. However, no clear associations of true small intestinal bacterial overgrowth with IBS or PPI use were detected, in contrast to recent speculation.     

Efficacy of rifaximin in the treatment of symptomatic diverticular disease of the colon. A multicentre double-blind placebo-controlled trial

Background and aims: In a recent open trial we have shown the efficacy of long term intermittent administration of a poorly absorbable antibiotic (rifaximin) in obtaining symptomatic relief in uncomplicated diverticular disease of the colon. The aim of this double-blind placebo-controlled trial was to test our previous observations. Methods: One hundred and sixty-eight outpatients with symptomatic uncomplicated diverticular disease were treated with fibre supplementation (glucomannan 2 g/day) plus rifaximin 400 mg b.d. for 7 days every month (84 patients), or with glucomannan 2 g/day plus placebo two tablets b.d. for 7 days every month (84 patients). Clinical evaluation was performed at admission and at three-month intervals for 12 months. Results: After 12 months, 68.9 % of the patients treated with rifaximin were symptom-free or mildly symptomatic, compared to 39.5% in the placebo group (P= 0.001). Symptoms such as bloating and abdominal pain or discomfort were primarily affected by antibiotic treatment when compared with placebo (P < 0.001). Conclusion: Rifaximin appears to be of some advantage in obtaining symptomatic relief in diverticular disease of the colon when compared with fibre supplementation alone.     

Rifaximin: a review of its use in the management of traveller's diarrhoea

Oral rifaximin, a semisynthetic rifamycin derivative, is an effective and well tolerated antibacterial for the management of adults with non-invasive traveller's diarrhoea. Rifaximin was significantly more effective than placebo and no less effective than ciprofloxacin in reducing the duration of diarrhoea after treatment initiation for illness contracted during travel to diverse geographic locations. While rifaximin is effective in patients with Escherichia coli-predominant traveller's diarrhoea, it appears ineffective in patients infected with inflammatory or invasive enteropathogens. Rifaximin has a broad spectrum of antibacterial activity in vitro and undergoes negligible systemic absorption (<0.4%). In contrast to systemically absorbed antibacterials, such as the fluoroquinolones and macrolides, the acquisition of resistance to rifaximin would have limited consequences for global public health, as rifaximin has no role in the management of systemic infections. Rifaximin shows promise as chemoprophylaxis against traveller's diarrhoea and is a valuable new option for the management of traveller's diarrhoea caused by non-invasive bacterial strains.     

The safety of novel drugs used to treat irritable bowel syndrome

Introduction: Irritable bowel syndrome (IBS) is a chronic gastrointestinal (GI) disorder with a high prevalence. Besides efficacy, the safety of each drugs used to treat GI disorders is an important issue in the drug development process.

Areas covered: This article reviews all Phase I to IV clinical trials or case reports with results related to the safety of novel GI drugs. The drugs are currently approved or under evaluation for approval.

Expert opinion: Most of the reported adverse events were related to the GI tract with mild-to-moderate severity. Diarrhea was significantly higher versus placebo following use of linaclotide and renzapride, similar to that of constipation with ramosetron. Lubiprostone, linaclotide and rifaximin with low systemic bioavailability have less adverse events and exert more advantageous results. Asimadoline acts peripherally on κ-opioid receptors and is not associated with CNS side effects. As lubiprostone and linaclotide cause dose-dependent adverse events, starting the treatment with the lowest effective doses is advised. Ramosetron is under evaluation for diarrhea-predominant IBS due to its acceptable safety and tolerability, besides its efficacy. Rifaximin, asimadoline and renzapride are still in need of more long-term studies regarding their safety.     

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome

BACKGROUND: The concept of augmenting the management of irritable bowel syndrome with antibiotics is evolving, and many questions remain regarding this therapy relative to known and hypothesized irritable bowel syndrome pathophysiology. The clinical evidence of small intestinal bacterial overgrowth as an important aetiology of irritable bowel syndrome continues to accumulate. Clinical symptoms of bacterial overgrowth and irritable bowel syndrome are similar; however, a definitive cause-and-effect relationship remains unproven. It is unclear whether motility dysfunction causes bacterial overgrowth or gas products of enteric bacteria affect intestinal motility in irritable bowel syndrome. AIM: To discusses the efficacy and tolerability of current symptom-directed pharmacotherapies and of antibiotics in the treatment of irritable bowel syndrome. METHODS: A computerized search of PubMed was performed with search terms "IBS", "pharmacotherapy" and "antibiotics". Relevant articles were selected, and the reference list of selected articles was reviewed to identify additional references. RESULTS: Antibiotic treatment benefits a subset of irritable bowel syndrome patients. The non-absorbed antibiotic rifaximin has a favourable safety and tolerability profile compared with systemic antibiotics and demonstrates a therapeutic efficacy comparable with symptom-based irritable bowel syndrome pharmacotherapies. CONCLUSION: Rifaximin is the only antibiotic with demonstrated sustained benefit beyond therapy cessation in irritable bowel syndrome patients in a placebo-controlled trial. Whether antibiotics can improve quality of life in patients with irritable bowel syndrome warrants further research.     

Safety and tolerability of the antibacterial rifaximin in the treatment of travellers' diarrhoea.

Although travellers' diarrhoea can sometimes be associated with postinfectious complications, the condition is typically self-limiting. The infectious-diarrhoea guidelines subcommittees of the Infectious Disease Society of America and the American College of Gastroenterology recommend empirical antibacterial therapy for travellers' diarrhoea. Because therapy is directed largely at relieving symptoms and minimising inconvenience, the chosen antibacterial should ideally be both efficacious and pose a low risk of adverse effects.This review discusses the safety and tolerability of rifaximin in the treatment of travellers' diarrhoea, with a focus on data from controlled clinical trials. Data were obtained from a MEDLINE search using the key word 'rifaximin' with no date limits and from the rifaximin New Drug Application submitted to the US FDA for approval to market rifaximin in the US.Currently, the antibacterials considered as standard treatment for travellers' diarrhoea are systemically absorbed, carry defined risks of adverse effects, and have many uses other than the treatment of enteric disease. The minimally absorbed (<0.4%) oral antibacterial rifaximin constitutes a non-systemic approach to antidiarrhoeal therapy that should overcome some of the limitations of current antibacterials used for travellers' diarrhoea. Rifaximin is differentiated from these, and most other antibacterials, by having a tolerability profile comparable with that of placebo and minimal potential for drug interactions. To date, clinically relevant resistance to rifaximin has not been observed. As the first nonabsorbable antibacterial to be marketed for travellers' diarrhoea, rifaximin should help to change the management paradigm for travellers' diarrhoea and other gastrointestinal illnesses from a systemic approach to a predictably safer, non-systemic approach.     

Rifaximin versus chlortetracycline in the short-term treatment of small intestinal bacterial overgrowth

BACKGROUND: Bacterial overgrowth of the small intestine is a condition characterized by nutrient malabsorption due to an excessive number of bacteria in the lumen of the small intestine. Current treatment is based on empirical courses of broad spectrum antibiotics; few controlled data, with respect to the duration and choice of antibiotic drug, exist at present. The recent availability of rifaximin, a non-absorbable rifamycin derivative, highly effective against anaerobic bacteria, prompted us to carry out a randomized, double-blind controlled trial in order to compare its efficacy and tolerability to those of tetracycline, currently considered the first-choice drug. METHODS: In 21 patients affected by small intestinal bacterial overgrowth, fasting, peak and total H2 excretion after ingestion of 50 g glucose and severity of symptoms were evaluated before and after a 7-day course of rifaximin, 1200 mg/day (400 mg t.d.s.), or chlortetracycline, 1 g/day (333 mg t.d.s. ). RESULTS: Fasting, peak and total H2 excretion decreased significantly in the group of patients treated with rifaximin whereas chlortetracycline did not modify these parameters. The H2 breath test normalized in 70% of patients after rifaximin and in 27% of patients after chlortetracycline. The improvement in symptoms was significantly higher in patients treated with rifaximin. CONCLUSIONS: Rifaximin is a promising, easily-handled and safe drug for the short-term treatment of small intestinal bacterial overgrowth.     

利福昔明治疗急性细菌性肠道感染107例

目的　评价利福昔明治疗急性细菌性肠道感染疾病的疗效和安全性。方法　采用多中心随机双盲双模拟平行对照试验。急性细菌性肠道感染患者 211例,随机分为两组,治疗组 107例,每次给予利福昔明 0. 2g,po,q6h,同时给予环丙沙星模拟安慰药片 1片,bid,疗程 5d;对照组 104例每次给予环丙沙星 0 .25g,po,bid,同时给予利福昔明模拟安慰药片 2片,po,q6h,疗程 5d。评价两药的疗效及不良反应。结果　治疗组肠道感染的治愈率和显效率分别是 75 7%和 18 .7%,总有效率为 94 .4%;对照组分别是 84 .6%和 13 .5%,总有效率为 98 .1%。利福昔明和环丙沙星的细菌清除率分别是 96. 2%和 96 3%,不良反应发生率为 2. 8%和 2. 9%。各项结果的差异均无显著性 (P>0 .05)。结论　利福昔明治疗急性细菌性肠道感染具有较好的疗效,不良反应发生率低,与环丙沙星的疗效相仿。     

利福昔明治疗急性感染性腹泻111例临床疗效及安全性

目的:评价利福昔明治疗急性感染性腹泻的临床疗效及安全性。方法:采用多中心、随机、双盲双模拟、阳性药物平行对照研究。入选急性感染性腹泻240例,完成227例,其中利福昔明组111例,男性52例,女性49例,年龄(30±s11)a,入组d1,服用利福昔明300mg和左氧氟沙星安慰剂1片,po,tid,d2~5,利福昔明400mg和左氧氟沙星安慰剂1片,po,bid;左氧氟沙星组116例,男性57例,女性59例,年龄(30±11)a,入组d1,服用左氧氟沙星100mg和利福昔明安慰剂3片,po,tid,d2~5,左氧氟沙星100mg和利福昔明安慰剂4片,po,bid。2组疗程均为3~5d。观察2组疗效和不良反应。结果:利福昔明组痊愈率和有效率分别为84.7%和100%,左氧氟沙星组痊愈率和有效率分别为77.6%和100%。2组疗效无统计学差异(P>0.05)。利福昔明组和左氧氟沙星组细菌清除率分别为100%和99%,2组无统计学差异(P>0.05)。2组均未出现不良反应。结论:利福昔明治疗急性感染性腹泻具有明显疗效,未见不良反应。     

Small intestine bacterial overgrowth in patients with irritable bowel syndrome

Recent investigations in patients with irritable bowel syndrome (IBS) undergoing a breath test (BT) with lactulose, have shown inconclusive results on a possible association between IBS and a small intestine bacterial overgrowth (SIBO), as well as on the effective prevalence of SIBO in IBS patients, because of different geographic areas involved and different criteria adopted for the BT positivity. The aim of this study was to estimate the prevalence of SIBO among IBS patients by means a lactulose BT. Between January 2005 and December 2006, all the patients who were sent to our Gastroenterology Unit by general practitioners (GPs) for "functional" gastrointestinal (GI) symptoms, underwent a lactulose BT for diagnosis of SIBO. The test was considered positive if the hydrogen concentrations in the expired air increased more than 20 ppm over basal values within 90 minutes. A total of 127 patients have been selected, 28 males and 99 females, aged between 17 and 76 (mean age: 41.4 years), with an IBS diagnosis based on the Roma II criteria. Fifty-five patients (43%) resulted positive to the lactulose BT. No significant difference was observed between IBS patients with (SIBO+) and without (SIBO-) an intestinal bacteria contamination. In conclusion, our results indicate that SIBO is relatively frequent in IBS patients and that execution of a lactulose BT should be encouraged in all these patients, being the only way to make correct diagnosis of SIBO and establish a valid therapeutic treatment.