BACKGROUND/AIMS: Ciprofloxacin has been widely prescribed for acute infectious diarrhea. However, the resistance to this drug is increasing. Rifaximin is a novel but poorly absorbed rifamycin derivative. This study evaluated and compared the efficacies of rifaximin and ciprofloxacin for the treatment of acute infectious diarrhea. METHODS: We performed a randomized controlled multicenter study in Korea. Patients with acute diarrhea were enrolled and randomized to receive rifaximin or ciprofloxacin for 3 days. The primary efficacy endpoint was the time to last unformed stool (TLUS). Secondary endpoints were enteric wellness (reduction of at least 50% in the number of unformed stools during 24-hour postenrollment intervals), general wellness (subjective feeling of improvement), and proportion of patients with treatment failure. RESULTS: Intent-to-treat analysis (n=143) showed no significant difference between the rifaximin and ciprofloxacin groups in the mean TLUS (36.1 hours vs 43.6 hours, p=0.163), enteric wellness (49% vs 57%, p=0.428), general wellness (67% vs 78%, p=0.189), or treatment failure rate (9% vs 12%, p=0.841). The adverse events did not differ significantly between the two groups. CONCLUSIONS: These results suggest that rifaximin is as safe and effective as ciprofloxacin in the treatment of acute infectious diarrhea.
Ciprofloxacin ; Diarrhea ; Humans ; Korea ; Rifamycins ; Treatment Failure

Abdominal bloating is a very common and troublesome symptom of all ages, but it has not been fully understood to date. Bloating is usually associated with functional gastrointestinal disorders or organic diseases, but it may also appear alone. The pathophysiology of bloating remains ambiguous, although some evidences support the potential mechanisms, including gut hypersensitivity, impaired gas handling, altered gut microbiota, and abnormal abdominal-phrenic reflexes. Owing to the insufficient understanding of these mechanisms, the available therapeutic options are limited. However, medical treatment with some prokinetics, rifaximin, lubiprostone and linaclotide could be considered in the treatment of bloating. In addition, dietary intervention is important in relieving symptom in patients with bloating.
Alprostadil ; Gastrointestinal Diseases ; Humans ; Hypersensitivity ; Metagenome ; Peptides ; Reflex ; Rifamycins ; Lubiprostone

BACKGROUND/AIMS: This study assessed the efficacy of a rifaximin plus levofloxacin-based rescue regimen in patients that had failed both triple and quadruple standard regimens for the eradication of Helicobacter pylori. METHODS: We treated patients for H. pylori between August 2009 and April 2011. The triple regimen consisted of combined treatment with amoxicillin, clarithromycin, and pantoprazole for 1 week. For failed cases, a quadruple regimen of tetracycline, metronidazole, bismuth dicitrate, and lansoprazole for 1 week was administered. The rescue regimen for persistently refractory cases was rifaximin 200 mg t.i.d., levofloxacin 500 mg q.d., and lansoprazole 15 mg b.i.d. for 1 week. RESULTS: In total, 482 patients were enrolled in this study. The eradication rates associated with the first and second regimens were 58% and 60%, respectively. Forty-seven out of 58 patients who failed with the second-line regimen received rifaximin plus levofloxacin-based third-line therapy. The eradication rate for the third regimen was 65%. The cumulative eradication rates were 58%, 85%, and 96% for each regimen, respectively. CONCLUSIONS: A rifaximin plus levofloxacin-based regimen could be an alternative rescue therapy in patients with resistance to both triple and quadruple regimens for the eradication of H. pylori.
2-Pyridinylmethylsulfinylbenzimidazoles ; Amoxicillin ; Bismuth ; Clarithromycin ; Helicobacter ; Helicobacter pylori ; Humans ; Metronidazole ; Ofloxacin ; Rifamycins ; Tetracycline

Oral antibiotics are usually prescribed for geriatric patients for the treatment of infectious diarrhea and management of hepatic encephalopathy. But oral antibiotics have systemic adverse events, so many doctors face the issue of choosing the right antibiotics. Rifaximin, an intestinal topical antibiotic that exhibits a wide antimicrobial activity against both aerobic and anaerobic bacteria, has various indications, such as acute bacterial diarrhea caused by Gram positive and negative bacteria, traveler's diarrhea, small intestine bacterial overgrowth, prevention of infection after gastrointestinal surgery, and the management of hepatic encephalopathy with hyperammoniemia. But there are few clinical trial data on the geriatric population. Hence we reviewed the clinical study data that included geriatric patients in their clinical trials. Based on our literature searches, only one clinical trial on acute bacterial diarrhea was performed only for geriatric patients. Other clinical trials for various indications usually recruited elderly patients, but the number of elderly patients was limited. However, generally speaking, rifaximin showed good efficacy and safety profile in acute bacterial diarrhea caused by Gram positive and negative bacteria, traveler's diarrhea, small intestine bacterial overgrowth, prevention of infection after gastrointestinal surgery, and the management of hepatic encephalopathy with hyperammoniemia; and there were no differences in efficacy and safety, compared to the nongeriatric population. We concluded that rifaximin is a good therapeutic option for various gastrointestinal indications, and shows good efficacy and an excellent safety profile, compared to other oral agents. For more evidence on the geriatric population, we propose clinical trials on elderly patients for each indication.
Aged ; Anti-Bacterial Agents ; Bacteria ; Bacteria, Anaerobic ; Diarrhea ; Hepatic Encephalopathy ; Humans ; Intestine, Small ; Rifamycins

Constipation, a common problem in gastroenterology practice, may result from slow colonic transit. Therapeutic options for slow transit constipations are limited. Excessive methane production by the methanogenic gut flora, which is more often found in patients with constipation, slows colonic transit. Thus, reduction in methane production with antibiotic treatment directed against methanogenic flora of the gut may accelerate colonic transit resulting in improvement in constipation. However, there is not much data to prove this hypothesis. We, therefore, report a patient with slow transit constipation associated with high methane production both in fasting state and after ingestion of glucose, whose constipation improved after treatment with non-absorbable antibiotic, rifaximin, which reduced breath methane values.
Breath Tests ; Colon ; Constipation ; Eating ; Fasting ; Gastroenterology ; Glucose ; Humans ; Hydrogen ; Irritable Bowel Syndrome ; Methane ; Rifamycins

Nitrate not only remarkably stimulates the rifamycinbiosynthesis in Amycolatopsis mediterranei, but also influences the primary metabolisms, including the inhibition of fatty acids biosynthesis in the bacterial. This phenomenon has been designated as "Nitrate Stimulating Effect" by the late Prof. J.S. Chiaosince its discovery in the 1970's, and has been found in many other antibiotics-producing actinomycetes subsequently. Based on the research in his laboratory, we have revealed that the nitrate stimulation effect mainly manifests in two aspects over the last two decades. First, nitrate promotes the supply of rifamycin precursors, e.g., UDP-glucose, AHBA, malonyl-CoA and methylmalonyl-CoA. Specifically, the biosynthesis of fatty acids is inhibited by nitrate consequently the acetyl-CoA is shunted into malonyl-CoA. Second, nitrate facilitates the expression of genes in the rifclulsterthat encodes rifamycin biosynthetic enzymes. Following our current understanding, the future research will focus on the signals, the signal transduction pathway and the molecular mechanisms that dictate nitrate-mediated transcriptional and post-translational regulations.
Actinomycetales ; classification ; metabolism ; Acyl Coenzyme A ; chemistry ; Anti-Bacterial Agents ; biosynthesis ; Nitrates ; chemistry ; Rifamycins ; biosynthesis

OBJECTIVE: To assess whether the same biological conclusion, diagnostic or curative effects regarding microbial composition of irritable bowel syndrome (IBS) patients could be reached through different bioinformatics pipelines, we used two common bioinformatics pipelines (Uparse V2.0 and Mothur V1.39.5)to analyze the same fecal microbial 16S rRNA high-throughput sequencing data. METHODS: The two pipelines were used to analyze the diversity and richness of fecal microbial 16S rRNA high-throughput sequencing data of 27 samples, including 9 healthy controls (HC group), 9 diarrhea IBS patients before (IBS group) and after Rifaximin treatment (IBS-treatment, IBSt group). Analyses such as microbial diversity, principal co-ordinates analysis (PCoA), nonmetric multidimensional scaling (NMDS) and linear discriminant analysis effect size (LEfSe) were used to find out the microbial differences among HC group vs. IBS group and IBS group vs. IBSt group. RESULTS: (1) Microbial composition comparison of the 27 samples in the two pipelines showed significant variations at both family and genera levels while no significant variations at phylum level; (2) There was no significant difference in the comparison of HC vs. IBS or IBS vs. IBSt (Uparse: HC vs. IBS, F=0.98, P=0.445; IBS vs. IBSt, F=0.47,P=0.926; Mothur: HC vs.IBS, F=0.82, P=0.646; IBS vs. IBSt, F=0.37, P=0.961). The Shannon index was significantly decreased in IBSt; (3) Both workshops distinguished the significantly enriched genera between HC and IBS groups. For example, Nitrosomonas and Paraprevotella increased while Pseudoalteromonadaceae and Anaerotruncus decreased in HC group through Uparse pipeline, nevertheless Roseburia 62 increased while Butyricicoccus and Moraxellaceae decreased in HC group through Mothur pipeline.Only Uparse pipeline could pick out significant genera between IBS and IBSt, such as Pseudobutyricibrio, Clostridiaceae 1 and Clostridiumsensustricto 1. CONCLUSION There were taxonomic and phylogenetic diversity differences between the two pipelines, Mothur can get more taxonomic details because the count number of each taxonomic level is higher. Both pipelines could distinguish the significantly enriched genera between HC and IBS groups, but Uparse was more capable to identity the difference between IBS and IBSt groups. To increase the reproducibility and reliability and to retain the consistency among similar studies, it is very important to consider the impact on different pipelines.
Case-Control Studies ; Computational Biology ; DNA, Bacterial/analysis* ; Diarrhea ; Feces ; Gastrointestinal Microbiome/genetics* ; Humans ; Irritable Bowel Syndrome/microbiology* ; Phylogeny ; RNA, Ribosomal, 16S ; Reproducibility of Results ; Rifamycins ; Rifaximin

Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patient's most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain.
Abdominal Pain ; Acupuncture ; Alprostadil ; Anti-Bacterial Agents ; Antidepressive Agents ; Carbolines ; Complementary Therapies ; Constipation ; Diarrhea ; Flatulence ; Gastrointestinal Diseases ; Humans ; Hypersensitivity ; Inflammation ; Irritable Bowel Syndrome ; Metagenome ; Parasympatholytics ; Placebos ; Probiotics ; Rifamycins ; Serotonin ; Biomarkers ; Lubiprostone

Hepatic encephalopathy, one of the major complications of cirrhosis, is a neuropsychiatric syndrome caused by accumulation of toxins in the central nervous system following dysfunction in liver detoxification. Various manifestations makes it difficulty to diagnose and categorize hepatic encephalopathy. For the consistency in diagnosis and staging of hepatic encephalopathy, standardized nomenclature regarding forms of hepatic encephalopathy was proposed recently. Due to the poor understanding of pathophysiology, effective prevention or treatment options are limited. Based on the theory that intestinal-derived ammonia plays major role in the development of hepatic encephalopathy, therapeutic approaches are directed at reducing intestinal bacterial production of ammonia and facilitating its elimination. Non-absorbable disaccharides, antibiotics such as rifaximin and L-ornithine-L-aspartate are main therapies for hepatic encephalopathy. Alternative therapies such as benzodiazepine receptor antagonists, branched-chain amino acids, sodium benzoate and acarbose have limited data supporting their use. Precipitating factors must be looked into carefully and corrected immediately because most patients are usually present with precipitating factors. Hepatic encephalopathy without precipitating factors shows poor prognosis and could be candidate of liver transplantation.
Acarbose ; Amino Acids, Branched-Chain ; Ammonia ; Anti-Bacterial Agents ; Central Nervous System ; Complementary Therapies ; Dipeptides ; Disaccharides ; Fibrosis ; Hepatic Encephalopathy ; Humans ; Liver ; Precipitating Factors ; Prognosis ; Receptors, GABA-A ; Rifamycins ; Sodium Benzoate

Rifaximin has been reported to be effective for the treatment of hepatic encephalopathy (HE) in Europe. However, it is unknown whether Rifaximin is effective for the treatment of HE in Koreans, therefore we conducted a open-label prospective randomized study to evaluate the efficacy of rifaximin versus lactulose in Korean patients. Fifty-four patients with liver cirrhosis and hepatic encephalopathy were enrolled. Thirty-two patients were randomized to receive rifaximin and 22 to receive lactulose both over a 7-day periods. Before and at the end of treatment, gradation of blood ammonia, flapping tremor, mental status, number connection test (NCT) were performed and estimation of HE indexes determined. Both rifaximin and lactulose were effective in the majority of patients (84.4% and 95.4%, respectively, p=0.315). Blood NH3, flapping tremor, mental status, and NCT was significantly improved by rifaximin and lactulose, and the post- treatment levels of these measures were similar for the rifaximin and lactulose-treated groups, as was the HE index (rifaximin group (10.0-->> 4.2, p=0.000) ; lactulose group (11.3-->> 5.0, p=0.000) ). One patient treated with rifaximin complained of abdominal pain, which was easily controlled. There was no episode of renal function impairment in either treatment group. Rifaximin proved to be as safe and as effective as lactulose for the treatment of Korean patients with hepatic encephalopathy.
Comparative Study ; Female ; Gastrointestinal Agents/*administration & dosage/adverse effects ; Hepatic Encephalopathy/*drug therapy ; Humans ; Lactulose/*administration & dosage/adverse effects ; Male ; Middle Aged ; Prospective Studies ; Research Support, Non-U.S. Gov't ; Rifamycins/*administration & dosage/adverse effects ; Treatment Outcome