How the North American Consensus Protocol Affects the Performance of Glucose Breath Testing for Bacterial Overgrowth Versus a Traditional Method.

INTRODUCTION: The North American Consensus guidelines for glucose breath testing (GBT) for small intestinal bacterial overgrowth (SIBO) incorporated changes in glucose dosing and diagnostic cutoffs. We compared GBT positivity based on hydrogen and methane excretion and quantified symptoms during performance of the North American vs older modified Rome Consensus protocols. METHODS: GBT was performed using the North American protocol (75 g glucose, cutoffs >20 parts per million [ppm] hydrogen increase after glucose and >10 ppm methane anytime) in 3,102 patients vs modified Rome protocol (50 g glucose, >12 ppm hydrogen and methane increases after glucose) in 3,193 patients with suspected SIBO. RESULTS: Positive GBT were more common with the North American vs modified Rome protocol (39.5% vs 29.7%, P < 0.001). Overall percentages with GBT positivity using methane criteria were greater and hydrogen criteria lower with the North American protocol (P < 0.001). Peak methane levels were higher for the North American protocol (P < 0.001). Times to peak hydrogen and methane production were not different between protocols. With the North American protocol, gastrointestinal and extraintestinal symptoms were more prevalent after glucose with both positive and negative GBT (P < 0.04) and greater numbers of symptoms (P < 0.001) were reported. DISCUSSION: GBT performed using the North American Consensus protocol was more often positive for SIBO vs the modified Rome protocol because of more prevalent positive methane excretion. Symptoms during testing were greater with the North American protocol. Implications of these observations on determining breath test positivity and antibiotic decisions for SIBO await future prospective testing.

ACG Clinical Guideline: Small Intestinal Bacterial Overgrowth.

Small intestinal bacterial overgrowth is defined as the presence of excessive numbers of bacteria in the small bowel, causing gastrointestinal symptoms. This guideline statement evaluates criteria for diagnosis, defines the optimal methods for diagnostic testing, and summarizes treatment options for small intestinal bacterial overgrowth. This guideline provides an evidence-based evaluation of the literature through the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process. In instances where the available evidence was not appropriate for a formal GRADE recommendation, key concepts were developed using expert consensus.

The Wireless Motility Capsule: a One-Stop Shop for the Evaluation of GI Motility Disorders.

The wireless motility and pH capsule (WMC) provides an office-based test to simultaneously assess both regional and whole gut transit. Ingestion of this non-digestible capsule capable of measuring temperature, pH, and the pressure of its immediate surroundings allows for the measurement of gastric, small bowel, and colonic transit times in an ambulatory setting. Approved by the US Food and Drug Administration for the evaluation of suspected conditions of delayed gastric emptying and the evaluation of colonic transit in chronic idiopathic constipation, WMC should be considered in suspected gastrointestinal motility disorders as it provides a single study capable of simultaneously assessing for regional, multiregional, or generalized motility disorders. Specific indications for testing with the WMC should include the evaluation of suspect cases of gastroparesis, small bowel dysmotility, and slow transit constipation, as well as symptom syndromes suggestive of a multiregional or generalized gastrointestinal transit delay.

Breath testing for small intestinal bacterial overgrowth: maximizing test accuracy.

The diagnosis of small intestinal bacterial overgrowth (SIBO) has increased considerably owing to a growing recognition of its association with common bowel symptoms including chronic diarrhea, bloating, abdominal distention, and the irritable bowel syndrome. Ideally, an accurate and objective diagnosis of SIBO should be established before initiating antibiotic treatment. Unfortunately, no perfect test exists for the diagnosis of SIBO. The current gold standard, small-bowel aspiration and quantitative culture, is limited by its high cost, invasive nature, lack of standardization, sampling error, and need for dedicated infrastructure. Although not without shortcomings, hydrogen breath testing provides the simplest noninvasive and widely available diagnostic modality for suspected SIBO. Carbohydrates such as lactulose and glucose are the most widely used substrates in hydrogen breath testing, with glucose arguably providing greater testing accuracy. Lactose, fructose, and sorbitol should not be used as substrates in the assessment of suspected SIBO. The measurement of methane in addition to hydrogen can increase the sensitivity of breath testing for SIBO. Diagnostic accuracy of hydrogen breath testing in SIBO can be maximized by careful patient selection for testing, proper test preparation, and standardization of test performance as well as test interpretation.

Do stool form and frequency correlate with whole-gut and colonic transit? Results from a multicenter study in constipated individuals and healthy controls.

OBJECTIVES: Despite a lack of supportive data, stool form and stool frequency are often used as clinical surrogates for gut transit in constipated patients. The aim of this study was to assess the correlation between stool characteristics (form and frequency) and gut transit in constipated and healthy adults. METHODS: A post hoc analysis was performed on 110 subjects (46 chronic constipation) from nine US sites recording stool form (Bristol Stool Scale) and frequency during simultaneous assessment of whole-gut and colonic transit by wireless motility capsule (WMC) and radio-opaque marker (ROM) tests. Stool form and frequency were correlated with transit times using Spearman's rank correlation. Accuracy of stool form in predicting delayed transit was assessed by receiver operating characteristic analysis. RESULTS: In the constipated adults (42 females, 4 males), moderate correlations were found between stool form and whole-gut transit measured by WMC (r=-0.61, P<0.0001) or ROM (-0.45, P=0.0016), as well as colonic transit measured by WMC (-0.62, P<0.0001). A Bristol stool form value <3 predicted delayed whole-gut transit with a sensitivity of 85% and specificity of 82% and delayed colonic transit with a sensitivity of 82% and specificity of 83%. No correlation between stool form and measured transit was found in healthy adults, regardless of gender. No correlation was found between stool frequency and measured transit in constipated or healthy adults. The correlation between stool frequency and measured transit remained poor in constipated adults with <3 bowel movements per week. CONCLUSIONS: Stool form predicts delayed vs. normal transit in adults. However, only a moderate correlation exists between stool form and measured whole-gut or colonic transit time in constipated adults. In contrast, stool frequency is a poor surrogate for transit, even in those with reduced stool frequency.

Heightened colon motor activity measured by a wireless capsule in patients with constipation: relation to colon transit and IBS.

Relationships of regional colonic motility to transit in health, constipation, and constipation-predominant irritable bowel syndrome (C-IBS) are poorly characterized. This study aimed to 1) characterize regional differences in colon pressure, 2) relate motor differences in constipation to colon transit, and 3) quantify the role of IBS in altered contractility with constipation. Colon pH and pressure were measured by wireless capsules in 53 healthy and 36 constipated subjects. Numbers of contractions >25 mmHg and areas under curves (AUC) were calculated for colon transit quartiles by time. Constipation was classified as normal transit (<59 h), moderate slow transit (STC) (59-100 h), and severe STC (>100 h). Twelve out of 36 constipated subjects had C-IBS; 24 had functional constipation. Numbers of contractions and AUCs increased from the first to the fourth quartile in health (P < 0.0001). Mean numbers of contractions in constipated subjects were similar to controls. Mean AUCs with normal transit (P = 0.01) and moderate STC (P = 0.004) but not severe STC (P = NS) were higher than healthy subjects. IBS was associated with greater mean numbers of contractions (P = 0.05) and AUCs (P = 0.0006) vs. controls independent of transit. Numbers of contractions increased from the first to fourth quartiles in moderate STC, C-IBS, and functional constipation; AUCs increased from the first to fourth quartiles in all groups (all P < 0.05). In conclusion, colon pressure activity is greater distally than proximally in health. Constipated patients with normal or moderately delayed transit show increased motor activity that is partly explained by IBS. These findings emphasize differential effects on transit and motility in different constipation subtypes.

Radiographic stool quantification: an equivalence study of 484 symptomatic and asymptomatic subjects.

PURPOSE: To determine if symptomatic patients referred for radiographic stool quantification have equivalent stool burden to asymptomatic patients. METHOD: This was an IRB-approved HIPAA-compliant retrospective equivalence cohort study. An a priori equivalence power calculation was performed. Consecutive abdominal radiographs performed in adult outpatients with bloating, constipation, diarrhea, or abdominal pain to assess "fecal loading" [n = 242 (fecal cohort)] were compared to those performed in asymptomatic adult outpatients to assess "renal stones" [n = 242 (renal cohort)]. Radiographs were randomized and reviewed by two blinded independent abdominal radiologists. Exclusion criteria, designed to avoid unblinding, included urinary tract calculi ≥ 0.5 cm, multiple urinary tract calculi, and ureteral stent(s). Readers scored all radiographs (n = 484) for stool burden using validated Leech criteria [scale: 0 (none) to 15 (extreme diffuse)]. Mean Leech scores and 95% confidence intervals were calculated. Multivariable generalized linear modeling was performed to adjust for baseline medication use, age, and gender. The adjusted parameter estimate was used to test for equivalence in the mean difference between cohorts using Schuirmann's method of two one-sided t-tests. Inter-reader agreement was assessed with intraclass correlation coefficients. RESULTS: Overall mean Leech scores for fecal [6.9 (95% CI 6.7, 7.2)] and renal [7.3 (95% CI 7.1, 7.5)] cohorts were equivalent within a margin of 0.75 (adjusted mean difference: - 0.4 [90% CI - 0.7, - 0.04]; p value = 0.02). Inter-reader agreement was good [ICC: 0.62 (95% CI 0.56, 0.68)]. CONCLUSION: Radiographic stool quantification produces equivalent results in symptomatic and asymptomatic adults and is of uncertain value.

Diabetes Mellitus and the Colon.

OPINION STATEMENT: Diabetes mellitus (DM) can affect the structure and function of the colon promoting commonly encountered lower gastrointestinal symptoms such as constipation, diarrhea, abdominal distention, bloating, and abdominal pain. Specific colonic disorders for which adults with DM are at greater risk include chronic constipation, enteropathic diarrhea, colorectal cancer (CRC), inflammatory bowel disease, microscopic colitis, and Clostridium difficile colitis. Smooth muscle structure and function, density of the interstitial cells of Cajal, and the health and function of the autonomic and enteric nerves of the colon are all potential affected by DM. These effects can in turn lead to alterations in colon motility, visceral sensation, immune function, endothelial function, and the colonic microbiome. The evaluation and treatment for slow transit constipation as well as pelvic floor dysfunction should be considered when constipation symptoms are refractory to initial treatment measures. DM-related medications and small bowel conditions such as celiac disease and small intestinal bowel overgrowth should be considered and excluded before a diagnosis of enteropathic diarrhea is made. Given the higher risk of CRC, adults with DM should be appropriately screened and may require a longer bowel preparation to ensure an adequate evaluation.

Peripherally acting therapies for the treatment of irritable bowel syndrome.

Gut-acting therapies are common therapies for irritable bowel syndrome (IBS). Most of these peripheral acting agents are primarily targeted at individual symptoms. The evidence supporting the use of these agents in IBS is largely anecdotal. Serotonergic agents and the chloride channel activator lubiprostone have shown efficacy in treating symptoms of IBS. The clinical evidence supporting the use of these agents is based on data from high-quality clinical trials. The use of serotonergic agents for IBS in the United States is limited to the 5-hydroxytryptamine-3 antagonist alosetron in the treatment of women with severe IBS with diarrhea refractory to traditional therapy.

A technical review and clinical assessment of the wireless motility capsule.

The wireless motility/pH capsule (WMC) is an orally ingested, nondigestible, data recording device that enables the simultaneous assessment of regional and whole gut transit. Approved by the US Food and Drug Administration for the evaluation of patients with suspected delayed gastric emptying and the evaluation of colonic transit time in patients with chronic idiopathic constipation, this capsule continuously measures the temperature, pH, and pressure of its surrounding environment while traveling through the gastrointestinal tract (via gut peristalsis) until exiting the body through the anus. Validated patterns in pH and temperature recordings allow for accurate measurement of gastric emptying, small bowel transit, colonic transit, and whole gut transit times. The WMC is a nonradioactive, office-based, gastrointestinal transit testing modality shown in several clinical trials to be a suitable alternative to scintigraphy and radiopaque marker studies in measuring gastric emptying, small bowel, colonic, and whole gut transit times. Unlike widely available transit tests, which provide only region-specific transit data, the WMC offers the benefit of measuring gastric, small bowel, and colonic transit times in a single examination. The WMC also provides intraluminal pressure readings throughout the digestive tract, offering a noninvasive means by which to assess gastrointestinal motility. The WMC should be considered the transit study of choice for individuals suspected of having altered transit in more than one region of the gastrointestinal tract. This review summarizes the features and performance characteristics of the WMC as well as provides a summary on how this diagnostic modality is most effectively used in the assessment of gastrointestinal symptom complexes due to suspected abnormalities in transit.

A clinician's guide to salvage therapy for persistent Helicobacter pylori infection.

Since its discovery in 1982, Helicobacter pylori has been established as a common cause of gastritis and peptic ulcer disease. H pylori infection is also closely associated with several gastric malignancies and has consequently been designated a human carcinogen. As these associations have become increasingly recognized and pursued, a growing challenge facing today's clinicians is the management of patients with persistent H pylori despite previous attempts to treat the infection. In developed countries, the most popular treatment regimen remains traditional triple therapy consisting of a proton pump inhibitor, clarithromycin, and amoxicillin for 7 to 14 days. Unfortunately, eradication rates with traditional triple therapy are disappointing, with infection persisting in as many as 25% of those treated. This article addresses the management of patients with persistent H pylori infection, including indications for confirmatory testing, reasons for treatment failure, and established and emerging salvage regimens for patients with persistent infection.

Recent developments in the therapy of irritable bowel syndrome.

There is tremendous activity and excitement in the arena of drug development for the treatment of the irritable bowel syndrome (IBS). Pharmacologic therapy has been largely limited to gut acting therapeutic agents including antidiarrheals, laxatives and antispasmodics that primarily target individual symptoms. Various antidepressants have gained popularity although their efficacy in clinical trials has been modest and their clinical utility is limited by untoward side effects. Serotonergic agents have demonstrated efficacy on the global symptoms of IBS; however, recent concerns about safety have severely limited their use. Recent discoveries regarding the pathophysiology of IBS have revealed numerous potential therapeutic targets. Agents under development include newer serotonergic agents and antidepressants; chloride channel, guanylate cyclase, opioid and motilin receptor ligands; various central, peripheral and autonomic neural receptor ligands; and gut immune modulators.

Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis.

BACKGROUND: Levofloxacin-based triple therapy has been suggested as an alternative salvage therapy to bismuth-based quadruple therapy for persistent Helicobacter pylori (H. pylori) infection. METHODS: A search of PUBMED, EMBASE, EBM Review databases and abstracts from recent Digestive Disease Week, United European Gastroenterology Week, and European Helicobacter Study Group conferences was performed. Randomized controlled trials (RCTs) comparing levofloxacin-based triple salvage therapy (levofloxacin + amoxicillin + PPI) to bismuth-based quadruple salvage therapy (bismuth + tetracycline + metronidazole + PPI) were selected for meta-analysis. Additionally, all prospective trials evaluating this levofloxacin-based triple therapy as salvage therapy were pooled to analyze optimal levofloxacin treatment duration and dosing. All selected trials confirmed prior treatment failure and post-salvage treatment eradication. RESULTS: Four RCTs compared a 10-day regimen of levofloxacin-based triple therapy to 7-day bismuth-based quadruple therapy (n = 391 patients). Levofloxacin-based triple therapy was superior to quadruple therapy (RR = 1.41 [95% CI: 1.25-1.59]). Levofloxacin-based triple therapy was better tolerated than quadruple therapy with a lower incidence of side effects (RR = 0.51 [95% CI: 0.34-0.75]) and side effects prompting discontinuation of therapy (RR = 0.30 [95% CI: 0.10-0.89]). Eleven trials (n = 547 patients) evaluating levofloxacin-based triple therapy demonstrated higher eradication rates with 10-day versus 7-day regimen (87%[95% CI: 82%-92%]vs 68%[95% CI: 62%-74%]) yet eight trials (n = 477 patients) demonstrated no difference with 500 mg daily versus 250 mg b.i.d. dosing of levofloxacin (81%[95% CI: 78%-89%]vs 84%[95% CI: 66%-97%]). CONCLUSIONS: A 10-day course levofloxacin triple therapy is more effective and better tolerated than 7-day bismuth-based quadruple therapy in the treatment of persistent H. pylori infection.