Sandra Sostarich

Efficacy of Rifaximin, a Nonabsorbed Oral Antibiotic, in the Treatment of Small Intestinal Bacterial Overgrowth

Introduction:Rifamixin is an orally administrated, nonabsorbed antibiotic whose utility in eradication of small intestinal bacterial overgrowth (SIBO) is currently being evaluated. Purpose:The aim of this study was to investigate efficacy and safety of rifaximin in relieving symptoms and normalizing the glucose breath test (GBT) in patients with SIBO. Methods:Symptom score assessment, consisting of frequency and severity of bloating, gas, abdominal pain, and bowel movements and the GBT were performed before and after treatment with rifaximin 800 mg/d for 4 weeks. Subjects:Twenty consecutive symptomatic patients (16 women and 4 men; mean age, 47.8 years; range, 19 to 85 years) who had a positive GBT were prospectively studied in an open-labeled fashion. Fourteen patients (70.0%) presented with diarrhea, 3 (15.0%) with bloating and gas, and 3 (15.0%) with constipation as the dominant symptom. Results:Eleven patients were hydrogen producers, 8 exclusively methane, and 1 patient produced both gases by the GBT. Among patients with diarrhea, 12 of 14 (85.7%) reported improvement in symptom scores of more than 50%; 1 between 25% and 50%, 1 had no response after 4 weeks of rifamixin. Among patients with bloating and gas or constipation as the main symptom: 2 of 6 (33.3%) had improvement between 50% and 75%; 3 (50%) had 25% to 50% improvement, and 1 (16.7%) had no response. Repeat GBT at the end of the 4 weeks showed that 54.5% of hydrogen formers and 50.0% of methane producers were eradicated, and there was a significant reduction (P <0.05) in the area under the concentration-time curve and peak values. No adverse effects were observed. Conclusions:Rifaximin in a dose of 800 mg per day for 4 weeks: 1) was safe and effective treatment in reducing symptoms in patients with SIBO of multiple etiologies, especially when diarrhea was the dominant symptom; and 2) normalized the GBT in approximately 50% of patients. Data support a future therapeutic role for rifaximin in SIBO.

Small intestinal bacterial overgrowth in irritable bowel syndrome: are there any predictors?

BackgroundSmall intestinal bacterial overgrowth (SIBO) is a condition in which excessive levels of bacteria, mainly the colonic-type species are present in the small intestine. Recent data suggest that SIBO may contribute to the pathophysiology of Irritable bowel syndrome (IBS). The purpose of this study was to identify potential predictors of SIBO in patients with IBS.MethodsAdults with IBS based on Rome II criteria who had predominance of bloating and flatulence underwent a glucose breath test (GBT) to determine the presence of SIBO. Breath samples were obtained at baseline and at 30, 45, 60, 75 and 90 minutes after ingestion of 50 g of glucose dissolved in 150 mL of water. Results of the glucose breath test, which measures hydrogen and methane levels in the breath, were considered positive for SIBO if 1) the hydrogen or methane peak was >20 ppm when the baseline was <10 ppm, or 2) the hydrogen or methane peak increased by 12 ppm when baseline was ≥10 ppm.ResultsNinety-eight patients were identified who underwent a GBT (mean age, 49 y; 78% female). Thirty-five patients (36%) had a positive GBT result suggestive of SIBO. A positive GBT result was more likely in patients >55 years of age (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.4-9.0) and in females (OR, 4.0; 95% CI, 1.1-14.5). Hydrogen was detected more frequently in patients with diarrhea-predominant IBS (OR, 8; 95% CI, 1.4-45), and methane was the main gas detected in patients with constipation-predominant IBS (OR, 8; 95% CI, 1.3-44). There was no significant correlation between the presence of SIBO and the predominant bowel pattern or concurrent use of tegaserod, proton pump inhibitors, or opiate analgesics.ConclusionsSmall intestinal bacterial overgrowth was present in a sizeable percentage of patients with IBS with predominance of bloating and flatulence. Older age and female sex were predictors of SIBO in patients with IBS. Identification of possible predictors of SIBO in patients with IBS could aid in the development of successful treatment plans.

Restorative Impact of Rabeprazole on Gastric Mucus and Mucin Production Impairment During Naproxen Administration: Its Potential Clinical Significance

Rabeprazole augments gastric mucus and mucin production in humans. However, its potential restorative impact on gastric mucus and mucin production impairment, resulting from administration of naproxen, remained to be explored. Therefore, we measured the content of mucus and mucin in gastric juice (GJ) before and after administration of naproxen with rabeprazole or placebo. The study was approved by HSC at KUMC and conducted in 21 asymptomatic, H. pylori–negative volunteers in a double-blind, placebo-controlled, crossover design. The content of gastric mucus in GJ, after exhaustive dialysis and complete lyophilization, was assessed gravimetrically, whereas the content of mucin was measured after its purification with equilibrium density-gradient ultracentrifugation in CsCl. Gastric mucus secretion during administration of naproxen with placebo declined significantly both in basal (by 44%; P < 0.001) and in pentagastrin-stimulated (by 35%; P < 0.001) conditions. Coadministration of rabeprazole significantly restored the naproxen-induced impairment in mucus production in basal conditions (by 47%; P < 0.01) and by 22% during stimulation with pentagastrin. Gastric mucin secretion during naproxen/placebo administration also declined significantly in both basal (by 39%; P < 0.01) and stimulated (by 49%; P = 0.003) conditions. Rabeprazole also significantly restored the naproxen-induced decline of gastric mucin output during pentagastrin-stimulated conditions (by 67%; P = 0.003) and by 40% in basal conditions (P = 0.05). The restorative capacity of rabeprazole on the quantitative impairment of gastric mucus and mucin during administration of naproxen may translate into a clinical benefit of protection of the upper alimentary tract from NSAID-related mucosal injury.

Significant enhancement of gastric mucin content after rabeprazole administration: its potential clinical significance in acid-related disorders.

Rabeprazole is the only proton pump inhibitor that enhances the content of gastric mucin in experimental animals. We have studied, therefore, the effect of rabeprazole on the content of gastric mucin, mucus, and its viscosity in 21 asymptomatic volunteers in a double-blind study. The mucus content during rabeprazole administration significantly increased both in pentagastrin-stimulated (3.36 ± 0.39 vs 1.50 ± 0.32 mg/ml, P < 0.001) and basal (3.31 ± 0.38 vs 2.28 ± 0.36 mg/ml, P < 0.01) conditions. The content of mucin during rabeprazole was 2.6-fold (0.96 ± 0.08 vs 0.36 ± 0.06 mg/ml, P < 0.0001) and 41% (0.82 ± 0.09 vs 0.58 ± 0.09 mg/ml, P < 0.05) higher in stimulated and basal conditions, respectively. The viscosity of gastric juice during rabeprazole administration was also significantly higher both in stimulated (P < 0.01) and basal (P < 0.05) conditions. In conclusion, the unique pharmacological property of rabeprazole, significantly augmenting production of gastric mucus and mucin, may translate to additional clinical benefits in protecting the upper alimentary tract mucosa during the acid-related challenge.

M1333 Irritable Bowel Syndrome and the Association With Small Intestinal Bacterial Overgrowth: Putting the Concept in Perspective

Aim: To explore triggers and warning sensations that precede diarrhea and how individuals make use of these. Methods: 579 individuals (68.6% female; ages 19-71, mean=30.5) with recurring diarrhea completed an internet survey including the Rome III diagnostic functional bowel disorders modules and a detailed questionnaire asking about diarrhea history, triggers, warning sensations and self-management. Individuals with inflammatory bowel disease, celiac disease, lactose intolerance or GI surgery history were excluded. Results: Most respondents (90.7%) had diarrhea at least 2-3 times per month. 23.7% had consulted health care providers about diarrhea. 70.5% met Rome III irritable bowel syndrome criteria but only 0.3% met functional diarrhea criteria. Diarrhea was self-defined by survey respondents, and typically considered to be characterized by loose/watery stools (92.5%), urgency (56.4%), pain/ discomfort (40.2%) and frequent stools (35.3%). 79.8% of subjects reported specific diarrhea triggers (i.e., actions or experiences they knew might result in diarrhea), and 44.0% stated that diarrhea resulted half or more of the times that these triggers occurred. Most common triggers were specific foods or drinks (72.3% of subjects), especially high-fat or spicy foods or caffeine beverages; stress/anxiety (49.7%); and large meals (25.2%). 83% of subjects with triggers rated stress/anxiety as the most frequent trigger. Nearly all subjects (95.6%) reported one or more types of physical warning sensations in advance of diarrhea, usually the same in nature for each subject and generally first occurring 10-25 minutes before diarrhea. The earliest warnings were typically either pain/discomfort (44.6%) or rumbling/bowel sounds (29.1%). 84.9% reported doing nothing to prevent or diminish diarrhea after warning sensations, but 15.1% used anti-diarrheal or antispasmodic drugs to counter the anticipated diarrhea. 74.4% used no medication once diarrhea started, 9.9% took medication early after onset, and 13.3% only later if it did not stop on its own. Warning sensations preceded at least half of all diarrhea bowel movements for 84.5% of subjects. Conclusions: Recognizable triggers and warning sensations precede diarrhea in most individuals, but few make efforts to prevent anticipated diarrhea. [Supported by McNeil Consumer Healthcare and R24 DK067674]

74 IS RIFAXIMIN EFFECTIVE TREATMENT FOR SMALL INTESTINAL BACTERIAL OVERGROWTH

Introduction Rifaximin is an orally administrated, nonabsorbed, nonsystemic antibiotic recently approved by the US Food and Drug Administration for travelers diarrhea. Its utility in eradication of small intestinal bacterial overgrowth (SIBO) is currently being evaluated. Purpose The aim of this study is to investigate efficacy and safety of rifaximin for bacterial eradication and relieving symptoms in patients affected by SIBO. Methods Treatment with rifaximin 200 mg qid was undertaken for 4 weeks. Assessment of a symptom score consisting of frequency and severity of bloating, gas, abdominal pain, and bowel movements was calculated at the beginning and after treatment. Glucose breath test (GBT) was also performed. Standard demographics were assessed. Subjects Ten consecutive symptomatic patients (8 F and 2 M, mean age of 53, range 19-85) were prospectively studied in an open-labeled fashion. Seven patients (70%) presented with diarrhea, 3 (30%) with bloating and gas as a dominant symptom. All patients had a > 20 ppm concentration of hydrogen and/or methane within 90 minutes of ingesting 50 g of glucose in 150 cc aqueous solution (GBT). Three subjects were exclusive methane formers, 1 methane and hydrogen, and 6 produced only hydrogen. Results Among patients with diarrhea 5 (71%) noticed improvement of more then 50%; 2 (29%) between 25 and 50%; 1 had no response after 4 weeks of rifaximin. Among patients with bloating + gas as the main symptom: 1 (33) had improvement between 50 and 75%; 1 (33%) between 25 and 50%, and 1 (33%) had no response. Repeat GBT in 6 patients at the end of the 4 weeks showed 50% of hydrogen formers and 67% of methane producers were eradicated. No adverse effects were observed. Conclusions This study shows that rifaximin in a dose of 200 mg qid for at least 4 weeks seems to be effective and safe treatment in reducing diarrhea and to a lesser degree gas + bloating in patients with SIBO. Further studies of follow-up breath test results and longer-term outcome are the next step in assessing this promising new therapy for SIBO.

Restorative impact of rabeprazole on gastric mucus production impairment during Naprosyn administration: its potential clinical significance

Restorative impact of rabeprazole on gastric mucus production impairment during Naprosyn administration: its potential clinical significance

Profoundly diminished gastric mucus production during Naprosyn administration as a potential factor contributing to mucosal injury

Profoundly diminished gastric mucus production during Naprosyn administration as a potential factor contributing to mucosal injury