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Background: Abdominal bloating is a common complaint in patients with functional and organic bowel disease. Rifaximin, a nonabsorbable antibiotic, has been tried for the treatment of this disease. We performed a systematic review and meta-analysis to study the efficacy of rifaximin in abdominal bloating and distension in patients with functional gastrointestinal disorders (FGID)., Methods: We accessed 4 databases (MEDLINE, Embase, SCOPUS, and Web of Science) to identify randomized placebo-controlled trials that utilized rifaximin in FGID. We excluded observational studies, those including patients with organic bowel disorders such as inflammatory bowel diseases, or those in which rifaximin was given for other indications, such as hepatic encephalopathy., Results: A total of 1426 articles were available, of which 813 articles were screened after removing duplicates and 34 articles were selected for full-text review. Finally, 10 trials (3326 patients) were included. Rifaximin was administered in doses ranging from 400 to 1650 mg per day for 1 to 2 weeks. Rifaximin therapy led to a higher likelihood of improvement in symptoms of bloating (44.6% vs. 34.6%, RR 1.22, 95% CI 1.11, 1.35; n=2401 patients) without significant heterogeneity. However, daily doses less than 1200 mg/day were similar to placebo ( P =0.09). Bloating was quantified subjectively in 7 studies, and rifaximin led to a greater reduction in bloating scores compared with placebo (standardized mean difference -0.3, 95% CI -0.51, -0.1, P =0.04) but carried significant heterogeneity ( I2 =61.6%, P =0.01)., Conclusions: Rifaximin therapy is associated with an increased likelihood of improvement in bloating and distension, as well as reduces the subjective severity of these symptoms in patients with FGID., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Hepatic encephalopathy (HE) is a major cause of morbidity in cirrhosis. However, its severity assessment is often subjective, which needs to be studied systematically. The aim was to determine how accurately trainee and nontrainee practitioners grade and manage HE patients throughout its severity. We performed a survey study using standardized simulated patient videos at 4 US and 3 Canadian centers. Participants were trainees (gastroenterology/hepatology fellows) and nontrainees (faculty, nurse practitioners, physician assistants). We determined the accuracy of HE severity identification and management options between grades <2 or ≥2 HE and trainees/nontrainees. In total, 108 respondents (62 trainees, 46 nontrainees) were included. For patients with grades <2 versus ≥2 HE, a higher percentage of respondents were better at correctly diagnosing grades ≥2 compared with grades <2 (91% versus 64%; P < 0.001). Specialized cognitive testing was checked significantly more often in grades <2, whereas more aggressive investigation for precipitating factors was ordered in HE grades >2. Serum ammonia levels were ordered in almost a third of grade ≥2 patients. For trainees and nontrainees, HE grades were identified similarly between groups. Trainees were less likely to order serum ammonia and low-protein diets, more likely to order rifaximin, and more likely to perform a more thorough workup for precipitating factors compared with nontrainee respondents. There was excellent concordance in the classification of grade ≥2 HE between nontrainees versus trainees, but lower grades showed discordance. Important differences were seen regarding blood ammonia, specialized testing, and nutritional management between trainees and nontrainees. These results have important implications at the patient level, interpreting multicenter clinical trials, and in the education of practitioners. Liver Transplantation 24 587-594 2018 AASLD., (© 2018 by the American Association for the Study of Liver Diseases.)

Decompensated cirrhosis is characterized by disturbed systemic and splanchnic hemodynamics. Bacterial translocation from the gut is considered the key driver in this process. Intestinal decontamination with rifaximin may improve hemodynamics. This double-blind, randomized, controlled trial (clinicaltrials.gov, NCT01769040) investigates the effects of rifaximin on hemodynamics, renal function, and vasoactive hormones. We randomized 54 stable outpatients with cirrhosis and ascites to rifaximin 550 mg twice a day (n = 36) or placebo twice a day (n = 18). Forty-five patients were male, mean age 56 years (±8.4), average Child score 8.3 (±1.3), and Model for End-Stage Liver Disease score 11.7 (±3.9). Measurements of hepatic venous pressure gradient, cardiac output, and systemic vascular resistance were made at baseline and after 4 weeks. The glomerular filtration rate and plasma renin, noradrenaline, lipopolysaccharide binding protein, troponin T, and brain natriuretic peptide levels were measured. Rifaximin had no effect on hepatic venous pressure gradient, mean 16.8 ± 3.8 mm Hg at baseline versus 16.6 ± 5.3 mm Hg at follow-up, compared to the placebo, mean 16.4 ± 4 mm Hg at baseline versus 16.3 ± 4.4 mm Hg at follow-up, P = 0.94. No effect was found on cardiac output, mean 6.9 ± 1.7 L/min at baseline versus 6.9 ± 2.3 L/min at follow-up, compared to placebo, mean 6.6 ± 1.9 L/min at baseline compared to 6.5 ±2.1 L/min at follow-up, P = 0.66. No effects on the glomerular filtration rate, P = 0.14, or vasoactive hormones were found. Subgroup analyses on patients with increased lipopolysaccharide binding protein and systemic vascular resistance below the mean (1,011 dynes × s/cm 5 ) revealed no effect of rifaximin., Conclusion: Four weeks of treatment with rifaximin did not reduce the hepatic venous pressure gradient or improve systemic hemodynamics in patients with cirrhosis and ascites; rifaximin did not affect glomerular filtration rate or levels of vasoactive hormones. (Hepatology 2017;65:592-603)., (© 2016 by the American Association for the Study of Liver Diseases.)

Microbes are mostly important for the digestion of food, the absorption of some micronutrients, and the production of vitamins. The microbiota stimulates lymphoid structures in the gastrointestinal mucosa and decrease pathogens by competing for nutrients and space. Bacterial translocation is defined as the escape of gut bacteria and their products through the intestinal mucosa to the outside of the intestine as portovenous or systemic circulation. This is induced by a leaky gut barrier. There is evidence for a role of intestinal permeability in the pathogenesis of nonalcoholic fatty liver disease. In the liver, bacterial products can bind to their specific pathogen recognition receptors on parenchymal and nonparenchymal cells, producing an inflammatory response and enhancing disease progression. When binding, bacterial products bind to their receptors, initiating intracellular signalling and inducing an inflammatory cascade, thus accelerating liver cell damage and fibrosis. However, the liver can also increase gut permeability, producing proinflammatory cytokines, and reversing them into the blood stream. Modification of the gut microbiota could lead to benefit in patients with liver disease. Nonabsorbable antibiotics (rifaximin) prevent and relieve overt encephalopathy. Probiotics alone are not capable of turning back overt encephalopathy, but could prevent its development. There is some evidence that probiotics could relent the progression of nonalcoholic liver disease, and possibly reverse steatosis. Antibiotics, such as fluoroquinolones, reduce the risk of development of the first episode of spontaneous bacterial peritonitis and mortality in cirrhotic patients.

Background: Management of diverticular disease (DD) remains a point of debate., Goals: To investigate the current opinion of participants of the 2nd International Symposium on Diverticular Disease, on real-life management of patients with DD of the colon., Study: Twelve questions were aimed at the diagnosis, treatment, and management options for diverticulosis and symptomatic DD., Results: In total, 115 surveys from 8 European Countries were filled out. High fiber diet was widely prescribed in diverticulosis (59.1%). Probiotics (25%) were the most frequent prescribed drug, whereas 29.8% of participants did not prescribe any treatment in diverticulosis. Colonoscopy was frequently prescribed in symptomatic patients (69.3%), whereas 72.9% of participants did not prescribe any instrumental tool in their follow-up. Rifaximin, probiotics, and mesalazine were the most frequent prescribed drugs both in symptomatic patients (28.1, 14.9%, and 11.4%, respectively) and to prevent recurrence of the disease (42.5%, 12.4%, and 28.2%, respectively). With respect to laboratory exams, 57.9% of participants prescribed them during follow-up. The majority of participants (64.9%) managed suspected acute diverticulitis at home. Rifaximin, probiotics, and mesalazine were the most frequent prescribed drugs to prevent recurrence of the disease (32.2%, 13.2%, and 11.4%, respectively), whereas 25.4% of participants did not prescribe any drugs. Finally, no differences were found among gastroenterologists, surgeons, and general practitioners in managing this disease., Conclusions: This surveys shows that current management of DD is similar between different medical specialities, generally in line with current literature.

Introduction: In routine colonoscopy, diverticulosis is the most commonly found feature, but only a minority of these cases show symptoms of diverticular disease.From June 2014 to December 2014, we enrolled prospectively 178 patients affected by symptomatic uncomplicated diverticular disease (Male/Female=0.47, mean age 71.7±11.5 y, range 41 to 95 y) from 15 General Pratictioners patient files. All patients were symptomatic; in all cases, diagnosis was been confirmed by a colonoscopy performed at least 1 year before. Patients with acute diverticulitis were excluded.On the basis of the predominant symptoms (abdominal complaints or constipation), patients were addressed to 4 different therapeutic approaches using mesalamine, rifaximine, probiotics (in a consortium of different species of Lactobacillus and Bifidobacterium), and fibers (Plantago Ovata Husk). All treatments lasted 3 months., Results: Sixty-three patients were enrolled in group A (rifaximine), 43 in group A1 (rifaximine+fibers+probiotics), 23 in group B (mesalamine), and 31 in group B1 (mesalamine+fibers).Analysis of variance suggested a statistically significant difference (P<0.003) among groups at the end of the observation period, with Groups A1 and B1 showing a higher number of bowel movement per week. Global linear measurement confirmed the role of treatment as a significant factor (F=2.858; P=0.039) associated with body mass index (F=6.972; P<0.009)., Conclusions: In accordance with the baseline clinical presentation, the supplementation of fiber and/or probiotics is associated with a statistically significant improvement in the clinical pattern of symptoms in patients with diverticular disease in a primary-care/family physician setting.

Diverticular disease (DD) of the colon represents the most common disease affecting the large bowel in western countries. Its prevalence is increasing. Recent studies suggest that changes in gut microbiota could contribute to development of symptoms and complication. For this reason antibiotics play a key role in the management of both uncomplicated and complicated DD. Rifaximin has demonstrated to be effective in obtaining symptoms relief at 1 year in patients with uncomplicated DD and to improve symptoms and maintain periods of remission following acute colonic diverticulitis (AD). Despite absence of data that supports the routine use of antibiotic in uncomplicated AD, they are recommended in selected patients. In patients with AD that develop an abscess, conservative treatment with broad-spectrum antibiotics is successful in up to 70% of cases. In patients on conservative treatment where percutaneous drainage fails or peritonitis develops, surgery is considered the standard therapy. In conclusion antibiotics seem to remain the mainstay of treatment in symptomatic uncomplicated DD and AD. Inpatient management and intravenous antibiotics are necessary in complicated AD, while outpatient management is considered the best strategy in the majority of uncomplicated patients.

Bacterial and fungal infections are major causes of morbidity and mortality after liver transplantation (LT). The role of intestinal decontamination in the prevention of post-LT infections is controversial. Rifaximin is widely used for the treatment of hepatic encephalopathy. The effect of rifaximin on post-LT infections is unknown. The aim of our study was to determine the effect of rifaximin therapy in the pretransplant period on early bacterial infections (EBIs) and fungal infections within the first 30 days after LT. All adult patients who underwent LT at our institution (January 2009 to July 2011) were included in this retrospective cohort study. Patients receiving antibiotics other than pretransplant protocol antibiotics were excluded. Patients were stratified into 2 groups based on the presence or absence of rifaximin therapy for at least 2 days before LT. Infections were defined by the isolation of any bacterial or fungal organisms within 30 days of LT. Multivariate regression analysis, Student t tests, and Pearson's chi-square tests were used to compare the 2 groups. Two hundred sixty-eight patients were included, and 71 of these patients (26.5%) were on rifaximin at the time of LT. The 2 groups were comparable with respect to age, sex, race, and Model for End-Stage Liver Disease score. There were no significant differences in the rates of EBIs (30% for the non-rifaximin group and 25% for the rifaximin group, P = 0.48) or fungal infections between the 2 groups. There was no increase in antimicrobial resistance among the infecting organisms. There was no difference in survival between the rifaximin and non-rifaximin groups (98% versus 97%, P = 0.36). In conclusion, the use of rifaximin in the pre-LT period was not associated with an increased risk of bacterial or fungal infections in the early post-LT period., (© 2014 American Association for the Study of Liver Diseases.)

Goals: The purpose of this study was to assess the incidence of Clostridium difficile infection in patients who received rifaximin for the treatment of hepatic encephalopathy (HE)., Methods: Medical charts of patients who received rifaximin for the treatment of HE were reviewed. The number of patients who developed diarrhea during treatment with rifaximin and results of latex agglutination assays to detect C. difficile in stool samples were analyzed., Results: A total of 211 patients received rifaximin for HE. Of these, 152 were treated in a university practice and 59 were treated in community practices. The mean dose of rifaximin was 1055 mg/d (range, 600 to 1600 mg/d) for a mean duration of 250 days (range, 180 to 385 d). Eighteen patients developed diarrhea during rifaximin treatment. None of these patients tested positive for C. difficile., Conclusions: This study demonstrates that treatment of HE with the safe, nonsystemic, gut-selective antibiotic rifaximin was not associated with the development of C. difficile infection.

Background: Primary prophylaxis of spontaneous bacterial peritonitis (SBP) may provide a survival advantage in cirrhotic patients with ascites and has become an integral part of clinical practice. Rifaximin is a poorly absorbable antibiotic with a broad spectrum of antibacterial action and has low risk of introducing bacterial resistance., Aim: To determine whether rifaximin is associated with decreasing the risk of SBP and improving transplant-free survival in cirrhotic patients with ascites., Methods: The medical records of all adult patients with liver cirrhosis and large ascites justifying paracentesis evaluated in our clinic (2003 to 2007) were reviewed. Patients were stratified into 2 groups by the use of rifaximin. Patients were excluded if they had received another antibiotic for SBP prophylaxis or had a history of SBP before rifaximin therapy., Results: A total of 404 patients were included, of whom 49 (12%) received rifaximin. The rifaximin and nonrifaximin groups were comparable with regards to age, sex, and race. The median follow-up time was 4.2 [1.0, 17.1] months. During this time period, 89% of patients on rifaximin remained SBP free compared with 68% of those not on rifaximin (P=0.002). After adjusting for Model of End-Stage Liver Disease score, Child-Pugh score, serum sodium, and ascitic fluid total protein, there was a 72% reduction in the rate of SBP in the rifaximin group (hazard ratio=0.28; 95% confidence interval, 0.11-0.71; P=0.007). The group treated with rifaximin also demonstrated a transplant-free survival benefit compared with those not on rifaximin (72% vs. 57%, P=0.045)., Conclusions: Intestinal decontamination with rifaximin may prevent SBP in cirrhotic patients with ascites. Prospective randomized controlled trials are needed to confirm this finding.

Unlabelled: Minimal hepatic encephalopathy (MHE) in cirrhosis is associated with impaired driving skills and increased risk of motor vehicle accidents (MVAs). Detection and treatment of MHE has the potential to reduce costs and morbidity associated with MVAs. We conducted a cost-effectiveness analysis to assess the benefits of different strategies of MHE diagnosis and treatment for reducing MVA-related societal costs. The analyses compared five MHE management strategies: (1) presumptive treatment of all cirrhosis patients; (2) diagnosis by neuropsychological exam (NPE) with treatment; (3) diagnosis by standard psychometric tests (SPTs) with treatment; (4) diagnosis by rapid screening using inhibitory control test (ICT) with treatment; and (5) no MHE diagnosis or treatment (status quo). Treatments considered were lactulose or rifaximin, which were assumed to reduce the MVA rate to the level of similarly aged noncirrhosis patients with benefit adjusted for treatment compliance. A Markov model followed a simulated cohort of 1,000 cirrhosis patients without overt hepatic encephalopathy (OHE), from entry into treatment, through MHE development, and later OHE, when they exited the modeled cohort. Follow-up was for 5 years and included biannual MHE testing. The societal cost of a single MVA was estimated at $42,100. All four strategies with lactulose were cost-saving compared with the status quo. Diagnosis with ICT and lactulose was the most cost-effective approach (cost/MVA prevented: $24,454 ICT; $25,470 SPT; $30,469 presumptive treatment and $33,742 NPE). Net program savings over 5 years ranged from $1.7 to 3.6 million depending on the strategy. Rifaximin therapy was not cost-saving at current prices but would become so at a monthly cost of <$353., Conclusion: Detection of MHE, especially using the ICT, and subsequent treatment with lactulose could substantially reduce societal costs by preventing MVAs., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Goals: To evaluate the durability of the response to rifaximin for treatment of hepatic encephalopathy (HE)., Background: The nonsystemic antibiotic rifaximin has been approved for maintenance of HE remission, and several studies have indicated the efficacy of rifaximin for acute HE; however, the duration of therapeutic response for >6 months remains unknown., Study: Medical records of patients with cirrhosis who received rifaximin maintenance therapy for HE between January 2004 and May 2009 were reviewed. Model for end-stage liver disease (MELD) scores were obtained every 3 months during therapy., Results: Of 203 patients with HE (Conn score ≥2), 149 received rifaximin monotherapy (400 to 1600 mg/d) and 54 received rifaximin (600 to 1200 mg/d) and lactulose (90 mL/d) dual therapy. Maintenance of HE remission for 1 year occurred in 81% and 67% of patients who received rifaximin monotherapy and rifaximin and lactulose dual therapy, respectively. Patient populations with a baseline mean MELD score ≤20 had few overt HE events, suggesting increased response to rifaximin in these patients., Conclusions: Rifaximin is effective for the management of HE in patients with cirrhosis, particularly in populations with MELD scores ≤20. Additional studies are needed to investigate the potential association between MELD scores and the efficacy of HE treatments.

Aim: There is a growing interest in methane and its association with constipation in functional bowel disease. Neomycin-based treatment of methane-positive subjects has resulted in improvement of constipation. Rifaximin, although superior for the treatment of irritable bowel syndrome compared with other antibiotics, seems less effective in methane-positive subjects. In this study, we evaluate 3 different antibiotic treatments in patients who have a methane-positive breath test: rifaximin only, neomycin only, and the combination of neomycin and rifaximin., Methods: A retrospective chart review was conducted on patients with methane on their lactulose breath test (> or =3 ppm of methane) who received one of the following antibiotic treatments: 500 mg b.i.d. for 10 days of neomycin alone, 400 mg t.i.d. for 10 days of rifaximin alone, or a combination of both rifaximin and neomycin for 10 days. All patients must have received antibiotic treatment after their initial consultation at the medical center and, in addition, had at least 1 follow-up to evaluate the effects of the treatment. After inclusion/exclusion criteria were met, all charts were evaluated to determine if the subject was a responder to the antibiotic therapy. This included clinical symptom improvement and eradication of methane on their breath test., Results: Of the subjects receiving the treatment of rifaximin and neomycin (n=27), 85% had a clinical response, compared with 63% of subjects in the neomycin only group (n=8) (P=0.15) and 56% of subjects in the rifaximin only group (n=39) (P=0.01). When comparing the neomycin group with the rifaximin group, the difference was nonsignificant. When evaluating methane eradication results, 87% of subjects taking the rifaximin and neomycin combination eradicated the methane on their breath test. This is compared with 33% of subjects in the neomycin group that eradicated the methane (P=0.001), and only 28% of subjects in the rifaximin group (P=0.001). Of the patients who did not eliminate the methane with only rifaximin treatment, 66% of those who subsequently used the rifaximin and neomycin treatment were able to normalize their breath test., Conclusions: The combination of rifaximin and neomycin is more effective in treating methane-producing subjects-in both clinical response and methane elimination.

Previous data have suggested that the nonsystemic antibiotic rifaximin may be effective for the treatment of Clostridium difficile infection (CDI). This single-center retrospective study evaluated the efficacy of rifaximin for the treatment of CDI refractory to standard treatments in patients who had received liver transplants. Among 205 patients who had received liver transplants between July 2001 and December 2007, 3 patients with a confirmed diagnosis of C. difficile experienced recurrent diarrhea even though they received standard therapy. Patient 1, a 56-year-old male, patient 2, a 62-year-old male, and patient 3, a 73-year-old female, developed CDIs 190, 318, and 2310 days after transplantation, respectively. All patients experienced symptom recurrences after oral metronidazole therapy (250 mg 3 times daily for either 14 or 28 days) and after oral vancomycin therapy (125 mg 4 times daily for 14 days). Long-term vancomycin treatment (ie, 28 days) was required for patients 1 and 2. Vancomycin was discontinued in patient 3 because of increased creatinine levels. Oral rifaximin (400 mg 3 times daily) was initiated immediately after discontinuation of vancomycin therapy. Within 36 to 48 hours of the initiation of rifaximin treatment, diarrheal symptoms were resolved in all patients. After completing a 28-day course of rifaximin, patient 1 remained symptom-free during 185 days of follow-up, and patient 2 remained symptom-free during 250 days of follow-up. Patient 3 reported no symptoms within 155 days after the completion of rifaximin treatment. These findings suggest that rifaximin may be effective for the treatment of recurrent CDI and may provide a therapeutic option for CDI in immunocompromised patients., ((c) 2010 AASLD.)

Background: Small intestinal bacterial overgrowth (SIBO) may mimic a functional disorder such as irritable bowel syndrome (IBS) or functional bloating (FB). In this study, we aimed to assess the utility of glucose breath test (GBT) in patients with the above conditions., Methods: This study included 200 consecutive patients (130 with IBS and 70 with FB on the basis of Rome III criteria) and 70 controls with similar age and sex distribution. Patients and controls underwent 50 g GBT and a H2 peak of > or = 12 ppm was considered diagnostic of SIBO. Positive patients received rifaximin of 1200mg/day for 10 days and underwent a second GBT 1 month after the end of treatment. A symptom questionnaire was completed before and after therapy., Results: GBT resulted to be altered in 21 out of 130 IBS patients and in 2 out of 70 FB patients with a significant difference of the former group compared with controls (3 out of 70, P=0.0137). Most IBS patients with a positive GBT complained of diarrhea. GBT showed an increased methane excretion in 26% of patients, who were equally distributed among different bowel pattern subgroups. Previous abdominal surgery was more frequently seen in GBT-positive patients (P=0.008). After antibiotic treatment, eradication of SIBO was achieved in 70% of patients, with a significant improvement of symptoms in eradicated patients compared with the not eradicated ones (P<0.001)., Conclusions: GBT is useful to identify a subgroup of IBS-like patients, whose symptoms are owing to SIBO. Normalization of GBT after antibiotic therapy is associated with a significant improvement of symptoms. GBT does not offer any advantage in FB patients.