Reviews for Primary Care - Fall 2007 - (Page 21) Chronic Constipation and Functional Bowel Disorders due to adverse events. It is obvious that newer therapeutic options are needed for many patients suffering from IBS-C. Additional Therapeutic Consideration for Constipation and IBS-C Efficacy of Probiotics in Patients With Constipation According to the World Health Organization, probiotics are living microorganisms which, when administered in adequate amounts, confer a health benefit on their host.47 There is some evidence suggesting that milk or yogurt fermented with different types of probiotics may reduce intestinal transit time and increase the daily stool number in constipated patients. In a parallel, double-blind, crossover study of 72 healthy adult women (mean age 30 years) who ingested fermented milk containing Bifidobacterium animalis (3 125 g/d) there was a decrease in total colonic transit time by 21% and decrease in sigmoid transit time by 39%.48,49 Although this study did not determine or indicate if the result was from the milk intake or the fermented bacteria, it does offer an insight into the potential effectiveness of probiotics in improving or normalizing colonic transit time. In another double-blind, placebocontrolled study, 70 patients with chronic constipation ingested a probiotic beverage containing Lactobacillus casei for 4 weeks.48 Individuals ingesting the probiotic had significant improvements in their reported severity of constipation and their stool consistency compared with individuals receiving placebo. Probiotics may be effective in patients with mild to moderate constipation.48 However, the effect of probiotic ingestion may be dependent on the bacterial strain used and the population being studied; therefore, at the current time, generalizations about the benefits of probiotic therapies cannot be made. Adverse events including cases of infection by Lactobacillus and Bifidobacterium organisms are extremely rare and are estimated to occur at a rate of approximately 0.05%-0.4% of all cases of infective endocarditis and bacteremia. Efficacy of Antibiotics on Patients With Constipation or IBS-C The use of antibiotics in patients with constipation or IBS-C is predicated on the notion that small intestinal bacterial overgrowth is associated with both of these disorders. Unfortunately, published clinical trials to date have utilized varying assessment methods, definitions, and inclusion criteria, which have resulted in mixed and controversial results. The largest and most current study looking at 162 patients with IBS by Posserud and colleagues concluded that small intestinal bacterial overgrowth does not play an important role in patients experiencing IBS; furthermore, motility alterations do not accurately predict small bowel bacterial flora.50 However, results did confirm that mildly increased counts of small bowel bacteria seem to be more common in patients with IBS. These results are in contrast to results from Pimentel and colleagues, who found that abnormal lactulose breath test (an indicator of small intestinal bacterial overgrowth) results were common in subjects with IBS, and that by normalizing the lactulose breath test via treatment with neomycin, patients will see significant reductions in IBS symptoms.51 Additionally, Pimentel and colleagues, in a recent subanalysis of patients with confirmed IBS-C (n 39) from his earlier study, were able to demonstrate a significant global improvement in IBS-C symptoms in subjects receiving neomycin (n 20) treatment compared with those receiving placebo (n 19) (P .001).52 Of the 12 patients in the original study (N 111) who had methane present in their breath tests, those receiving neomycin had significant improvements in constipation (P .05). Sharara and colleagues conducted a randomized, double-blind, placebocontrolled trial in 124 patients experiencing symptoms of bloating and flatulence.53 The study was broken into 3 10-day phases: phase 1 (baseline), phase 2 (treatment with rifaximin 400 mg twice daily or placebo), and phase 3 (posttreatment period). The primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. At the end of phase 2 (active treatment), there was a significant difference in global symptom relief with rifaximin compared with placebo (41.3% vs 22.9%; P .03) but not in bowel habits.53 This improvement was maintained at the end of phase 3 (28.6% vs 11.5%; P .02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (P .05). Among patients who also met symptom-based criteria for IBS, a favorable response to rifaximin was noted (40.5% vs. 18.2%; P .04) that persisted through the end of phase 3 (27% vs 9.1%; P .05). H2breath excretion decreased significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (P .01). Currently, due to the controversial results demonstrated in published clinical trials to date, the importance of small intestinal bacterial overgrowth and bacteria in other parts of the gut for functional gastrointestinal symptoms remains to be determined.54 VOL. 1 NO. 1 2007 REVIEWS FOR PRIMARY CARE 21
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