Effect of rifaximin on intestinal bacterial overgrowth in Crohn's disease as assessed by the H2-Glucose Breath Test

The occurrence of intestinal bacterial overgrowth in patients with Crohn's Disease (CD) has been described and antimicrobial treatment has been shown to be effective in reversing this condition. However, the mechanisms underlying the efficacy of antimicrobial therapy are still only partially known. The aim of the present study was to evaluate the effect of a non-absorbable antibiotic (rifaximin) in comparison to placebo on bacterial overgrowth in patients with CD. METHODS: Fourteen patients with inactive CD of the ileum and bacterial overgrowth, as assessed by the hydrogen breath test, were blindly allocated to receive rifaximin (1200 mg/day) or placebo t.i.d. for one week. A hydrogen breath test, and clinical and biochemical parameters were further performed 14 days and 30 days after starting treatment. RESULTS: After 14 days, the hydrogen breath test proved to be negative in seven out of seven patients treated with rifaximin (p < 0.05), and in two out of seven in the placebo group (p = ns). After 30 days, the hydrogen breath test was positive in all patients of the rifaximin and placebo group, respectively. No changes in the CDAI score were documented in any patients. CONCLUSIONS: Short-term administration of rifaximin is effective in the therapy of bacterial overgrowth in patients with inactive CD of the ileum, thus suggesting that the control of luminal bacterial growth could be useful in the management of these patients. However, since we observed a decline with time in this positive effect, further studies are needed to identify the most appropriate therapeutic strategies.     

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 dose-finding study for the treatment of small intestinal bacterial overgrowth

BACKGROUND: Few controlled studies assessing choice and duration of antibiotic therapy for small intestinal bacterial overgrowth are available. AIM: To assess efficacy, safety and tolerability of different doses of rifaximin, a broad spectrum non-absorbable antibiotic, for intestinal bacterial overgrowth eradication. METHODS: We enrolled 90 consecutive patients affected by small intestinal bacterial overgrowth. The presence of small intestinal bacterial overgrowth was based on the occurrence of a rise of H2 values >12 p.p.m. above the basal value after 50 g glucose ingestion. Patients were randomized in three 7-day treatment groups: rifaximin 600 mg/day (group 1); rifaximin 800 mg/day (group 2) and rifaximin 1200 mg/day (group 3). Glucose breath test was reassessed 1 month after the end of therapy. Compliance to the treatment and incidence of side-effects were also evaluated. RESULTS: No drop-outs were observed in the three groups. Glucose breath test normalization rate was significantly higher in group 3 (60%) with respect to group 1 (17%; P < 0.001) and group 2 (27%, P < 0.01). No significant differences in patient compliance and incidence of side-effects were found among groups. CONCLUSIONS: Higher doses of rifaximin lead to a significant gain in terms of therapeutic efficacy in small intestinal bacterial overgrowth eradication without increasing the incidence of side-effects.     

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.     

Abnormal breath tests to lactose, fructose and sorbitol in irritable bowel syndrome may be explained by small intestinal bacterial overgrowth

BACKGROUND: Small intestinal bacterial overgrowth and sugar malabsorption (lactose, fructose, sorbitol) may play a role in irritable bowel syndrome. The lactulose breath test is a reliable and non-invasive test for the diagnosis of small intestinal bacterial overgrowth. The lactose, fructose and sorbitol hydrogen breath tests are widely used to detect specific sugar malabsorption. AIM: To assess the extent to which small intestinal bacterial overgrowth may influence the results of hydrogen sugar breath tests in irritable bowel syndrome patients. METHODS: We enrolled 98 consecutive irritable bowel syndrome patients. All subjects underwent hydrogen lactulose, lactose, fructose and sorbitol hydrogen breath tests. Small intestinal bacterial overgrowth patients were treated with 1-week course of antibiotics. All tests were repeated 1 month after the end of therapy. RESULTS: A positive lactulose breath test was found in 64 of 98 (65%) subjects; these small intestinal bacterial overgrowth patients showed a significantly higher prevalence of positivity to the lactose breath test (P < 0.05), fructose breath test (P < 0.01) and sorbitol breath test (P < 0.01) when compared with the small intestinal bacterial overgrowth-negatives. Small intestinal bacterial overgrowth eradication, as confirmed by negative lactulose breath test, caused a significant reduction in lactose, fructose and sorbitol breath tests positivity (17% vs. 100%, 3% vs. 62%, and 10% vs. 71% respectively: P < 0.0001). CONCLUSIONS: In irritable bowel syndrome patients with small intestinal bacterial overgrowth, sugar breath tests may be falsely abnormal. Eradication of small intestinal bacterial overgrowth normalizes sugar breath tests in the majority of patients. Testing for small intestinal bacterial overgrowth should be performed before other sugar breath tests tests to avoid sugar malabsorption misdiagnosis.     

Evaluation of the effect of rifaximin in colon diverticular disease by means of lactulose hydrogen breath test

Summary

To understand better the mechanism by which rifaximin produces symptomatic relief in diverticular disease of the colon, the effect of this antibiotic on orocaecal transit time and on the production of hydrogen by intestinal microflora after ingestion of lactulose was studied in 33 patients with this disease and in 11 healthy subjects. An hydrogen breath test was carried out to measure pulmonary hydrogen excreted during the 3 hours after ingestion of 10?g lactulose. In patients, the hydrogen breath test with lactulose was repeated after treatment with 400?mg rifaximin twice daily for 10 days. In patients under basal conditions and controls, orocaecal transit time did not differ significantly, but hydrogen production was significantly higher in the former (p<0.02). In patients, transit time and hydrogen excretion in response to lactulose administration did not differ significantly before and after treatment with rifaximin, and these two parameters were inversely correlated both before (r=0.49, p<0.01) and after rifaximin (r=0.58, p<0.001). Fifteen of the 33 patients showed accelerated transit time after treatment with the antibiotic, 10 showed no variation, and 8 showed prolonged transit. In 19 patients a reduction in hydrogen production was noted after rifaximin, while in 14 an increase was demonstrated. Twenty-one of the 33 patients reported an improvement in their symptoms with rifaximin; of these, only 10 showed accelerated transit time and 9 a reduction in hydrogen production after rifaximin. The results indicate that, while an increase in pulmonary hydrogen excretion is evident in diverticular disease, the therapeutic effect of rifaximin does not seem to be due to a persistent correction of this alteration. In addition, this drug appears to cause no significant imbalance in the intestinal ecosystem.     

Absorbable vs. non-absorbable antibiotics in the treatment of small intestine bacterial overgrowth in patients with blind-loop syndrome

BACKGROUND: Small intestine bacterial overgrowth is associated with the presence of predisposing conditions, acting through different mechanisms. Therefore, the failure to define a standardized therapy may be due to a methodological bias: to treat a condition characterized by different pathophysiological mechanisms with the same pharmacological approach. Non-absorbable antibiotics could have a lower efficacy than absorbable drugs in patients with blind loops which exclude a portion of the intestine from the transit. AIM: To evaluate the efficacy of absorbable vs. non-absorbable antibiotics in this subgroup of patients. METHODS: A group of small intestine bacterial overgrowth patients with total gastrectomy or gastrojejunostomy and blind loop underwent a therapeutic trial comparing rifaximin to metronidazole. Seven patients underwent a course of rifaximin followed by a course of metronidazole on recurrence of symptoms. To compare the effect of the drugs, another two groups of patients underwent two consecutive courses of rifaximin or metronidazole. Hydrogen breath test after glucose administration and symptom severity measurement were performed. RESULTS: Both drugs reduced breath H(2) excretion but a much better improvement was achieved after metronidazole. Symptom improvement was higher after metronidazole. CONCLUSION: Metronidazole is more effective than rifaximin for the treatment of small intestine bacterial overgrowth associated with the presence of a blind loop.     

Interaction between rifaximin and dietary fibre in patients with diverticular disease

BACKGROUND: Cyclic administration of rifaximin in association with dietary fibre achieves symptomatic relief in uncomplicated diverticular disease (DD) by means of a still undefined mechanism. AIM: To investigate the effects of a combination of rifaximin and fibre on both hydrogen production by intestinal microflora and oro-anal transit time. METHODS: In a controlled, double-blind crossover trial, 64 patients with uncomplicated DD were given bran (20 g/day) and randomly treated with rifaximin (1200 mg/day) or a placebo for 14 days. Evaluation was based on clinical status, breath test, oro-anal transit time and faecal weight. RESULTS: The global symptomatic score was significantly reduced after rifaximin (7.1 +/- 4.1 to 4.1 +/- 3.3; P < 0.005) but not after placebo (6.8 +/- 3.8 to 6.1 +/- 3.5). Hydrogen production significantly increased after placebo from 198 +/- 134 to 267 +/- 161 ppm/min, while Rifaximin reduced it from 222 +/- 187 to 166 +/- 131 ppm/min (P = 0.05). The total oro-anal transit time decreased from 56.1 +/- 28.2 to 51.3 +/- 28.0 h in placebo and from 54.4 +/- 31.9 to 45.1 +/- 32.4 h (P < 0.05) in rifaximin-treated patients. CONCLUSIONS: The administration of rifamixin improves the benefits of dietary fibre in uncomplicated DD by preventing its bacterial degradation.     

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.     

Non-absorbable antibiotics for managing intestinal gas production and gas-related symptoms

BACKGROUND: Simethicone, activated charcoal and antimicrobial drugs have been used to treat gas-related symptoms with conflicting results. AIM: To study the relationship between gaseous symptoms and colonic gas production and to test the efficacy of rifaximin, a new non-absorbable antimicrobial agent, on these symptoms. METHODS: Intestinal gas production was measured by hydrogen (H2) and methane (CH4) breath testing after lactulose in 21 healthy volunteers and 34 functional patients. Only the 34 functional patients took part in a double-blind, double-dummy controlled trial, receiving, at random, rifaximin (400 mg b.d per 7 days), or activated charcoal (400 mg b.d per 7 days). The following parameters were evaluated at the start of the study and 1 and 10 days after therapy: bloating, abdominal pain, number of flatus episodes, abdominal girth, and cumulative breath H2 excretion. RESULTS: Hydrogen excretion was greater in functional patients than in healthy volunteers. Rifaximin, but not activated charcoal, led to a significant reduction in H2 excretion and overall severity of symptoms. In particular, in patients treated with rifaximin, a significant reduction in the mean number of flatus episodes and of mean abdominal girth was evident. CONCLUSIONS: In patients with gas-related symptoms the colonic production of H2 is increased. Rifaximin significantly reduces this production and the excessive number of flatus episodes.     

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.     

Intestinal bacterial overgrowth during chronic pancreatitis

INTRODUCTION: The presence of an intestinal bacterial overgrowth (IBO) in patients with pancreatic insufficiency has been recently suggested to justify the worsening of their clinical conditions despite pancreatic enzyme supplementation. AIM: The purposes of this study were (a) to verify IBO frequency in patients with pancreatic insufficiency owing to chronic pancreatitis and (b) to evaluate the effect of chronic administration of a non-absorbable antibiotic, Rifaximin, in reducing IBO frequency and influencing the clinical picture of the disease. MATERIAL AND METHODS: Thirty-five patients with pancreatic insufficiency owing to chronic pancreatitis and 61 gastro-resected patients without pancreatic disease were studied. The presence of IBO was tested in both groups of patients using the hydrogen breath test with glucose. Chronic pancreatitis patients were subsequently treated with Rifaximin, 400 mg t.i.d for seven consecutive days each month for three months. RESULTS: A positive hydrogen breath test was present in 12 out of 35 (34%) chronic pancreatitis patients and in 13 out 61 (21%) controls (p < 0.002). In chronic pancreatitis patients an IBO was most likely to be present in the presence of a high ethanol intake, pancreatic microcalcifications, concomitant gallstones, diarrhoea and a history of gastric resection. In all patients with IBO, Rifaximin administration normalised the hydrogen breath test and reduced symptoms. CONCLUSIONS: IBO is frequent in patients with pancreatic insufficiency, particularly in those with a history of gastroduodenal surgery. Treatment with Rifaximin reduces IBO frequency and improves symptoms.     

The benefit of pancreatic enzyme substitution after total gastrectomy

The aim of the present study was to evaluate the effect of the pancreatic enzyme preparation Kreon on abdominal symptoms, bowel habits, faecal fat excretion and oro-caecal transit time in patients after total gastrectomy for carcinoma of the stomach with Roux-en-Y anastomosis. A hydrogen breath test was carried out in each patient to detect bacterial overgrowth. In a double-blind crossover trial, 15 patients were treated with either Kreon or placebo (3.6 g/day) in two test-periods each of seven days. During treatment with the active substance, the stool consistency became more solid (P less than 0.05). The number of bowel movements and the abdominal symptoms, however, remained statistically unchanged. Treatment with Kreon did not influence the oro-caecal transit time. Faecal fat excretion did not significantly decrease in the whole group of patients. However, in those patients with massive steatorrhoea (free and esterified fatty acids greater than 350 mmol/72 h; upper reference limit 60 mmol/72 h) a significant (P less than 0.05) reduction from a median excretion of 643 mmol/72 h to 501 mmol/72 h was seen. Such a decrease in faecal fat excretion did not occur in patients with steatorrhoea below this limit. Bacterial overgrowth or rapid upper intestinal transit were not over-represented in patients with a high-degree of steatorrhoea. We conclude that after total gastrectomy pancreatic enzyme substitution reduces massive steatorrhoea and improves stool consistency.     

Hydrogen glucose breath test to detect small intestinal bacterial overgrowth: a prevalence case-control study in irritable bowel syndrome

BACKGROUND: Studies assessing the prevalence of small intestinal bacterial overgrowth in irritable bowel syndrome gave contrasting results. Differences in criteria to define irritable bowel syndrome patients and methods to assess small intestinal bacterial overgrowth may explain different results. Moreover, no data exist on small intestinal bacterial overgrowth prevalence in a significant population of healthy non-irritable bowel syndrome subjects. AIM: To assess the prevalence of small intestinal bacterial overgrowth by glucose breath test in patients with irritable bowel syndrome symptoms with respect to a consistent control group. METHODS: Consecutive patients with irritable bowel syndrome according to Rome II criteria were enrolled. The control population consisted of 102 sex- and age-matched healthy subjects without irritable bowel syndrome symptoms. All subjects underwent glucose breath test. A peak of H2 values >10 p.p.m above the basal value after 50 g of glucose ingestion was considered suggestive of small intestinal bacterial overgrowth. RESULTS: A total of 65 irritable bowel syndrome patients and 102 healthy controls were enrolled. Positivity to glucose breath test was found in 31% of irritable bowel syndrome patients with respect to 4% in the control group, the difference between groups resulting statistically significant (OR: 2.65; 95% CI: 3.5-33.7, P < 0.00001). CONCLUSIONS: The present case-control study showed an epidemiological association between irritable bowel syndrome and small intestinal bacterial overgrowth. Placebo-controlled small intestinal bacterial overgrowth-eradication studies are necessary to clarify the real impact of small intestinal bacterial overgrowth on irritable bowel syndrome symptoms.     

Antibiotic treatment of small bowel bacterial overgrowth in patients with Crohn's disease

BACKGROUND: Small bowel bacterial overgrowth is common in Crohn's disease but its treatment is not clearly defined. Metronidazole and ciprofloxacin are effective antibiotics in active Crohn's disease. AIM: To investigate the efficacy of metronidazole and ciprofloxacin in the treatment of bacterial overgrowth in patients with Crohn's disease. PATIENTS AND METHODS: We performed the lactulose breath test in 145 consecutive patients affected by Crohn's disease. Patients positive to the lactulose breath test underwent a glucose breath test to confirm the overgrowth. These patients were randomized in two treatment groups: metronidazole 250 mg t.d.s. (Group A) and ciprofloxacin 500 mg b.d. (Group B), both orally for 10 days. The glucose breath test was repeated at the end of treatment. The clinical outcome after therapy was also recorded. RESULTS: Bacterial overgrowth was present in 29 patients (20%). Breath test normalization occurred in 13 out of 15 patients treated by metronidazole and in all 14 patients treated by ciprofloxacin (P = ns). In both groups antibiotic treatment induced an improvement of intestinal symptoms: bloating (Group A 85% and Group B 83%), stool softness (44% and 50%), and abdominal pain (50% and 43%). CONCLUSIONS: Small bowel bacterial overgrowth is a frequent condition in Crohn's disease which can be effectively treated by metronidazole or ciprofloxacin.     

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 treatment of pathogen-negative travelers' diarrhea

BACKGROUND: Antibacterial drugs appear to be effective in shortening the illness of a majority of cases of travelers' diarrhea. METHODS: This was a subanalysis from two randomized, double-blind, placebo-controlled trials in adult travelers with acute diarrhea treated with rifaximin 200 mg three times a day or placebo for 3 days. Efficacy was assessed by the interval beginning with the first dose of medication and ending with the last unformed stool passed after becoming well [time to last unformed stool (TLUS)]; number of unformed stools passed; percent with clinical improvement; and incidence of wellness achieved. RESULTS: Stool pathogens were not identified in pretreatment samples in 122 of 322 (38%) patients and 106 of 230 (46%) randomized to rifaximin and placebo, respectively. Among pathogen-negative patients, rifaximin was more effective than placebo for median TLUS (33 vs 68 h, p < 0.005), mean number of unformed stools passed (6.5 vs 8.6, p < 0.0001), and clinical wellness (77% vs 61%, p = 0.01). The adverse-event profiles between rifaximin and placebo were similar. CONCLUSIONS: More than one third of patients with travelers' diarrhea had pathogen-negative illness. Rifaximin was effective in treating the illness without associated side effects. These results are consistent with the hypothesis that undetected bacterial pathogens are the most likely cause of travelers' diarrhea without definable cause.     

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.     

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,a non-absorbable rifamycin,for the treatment of hepatic encephalopathy. A double-blind,randomised trial

Summary

The aim of this study was to evaluate the efficacy and tolerability of rifaximin, a non-absorbable intestinal antibiotic, in comparison to neomycin in the short- and long-term treatment of hepatic encephalopathy (HE). Forty-nine patients with a definite diagnosis of cirrhosis were included in this double-blind, randomised, controlled trial. Patients were randomly assigned to one of the following treatments: (1) rifaximin 400?mg three times daily: (2) neomycin 1?g three times daily. Both drugs were administrated orally as tablets during 14 consecutive days each month, for a period of six months.

The neuropsychiatric signs and blood ammonia levels were examined before starting the treatment, and every 30 days, until the final assessment.

In all patients a progressive and important reduction in HE grade was observed, and no statistically significant difference between the two treatments was detected.

In both groups the disturbances in speech, memory, behaviour and mood, gait, asterixis, writing, and serial subtraction of 7s and five-pointed star tests all showed the highest proportion of improvement.

During the study blood ammonia levels decreased in both the rifaximin and in the neomycin groups, and again no statistically significant difference was found between groups.

Our findings confirm, therefore, the usefulness of rifaximin in the treatment of HE, supporting its use as a first-choice antibiotic, particularly in patients intolerant to neomycin or with impaired renal function.