Abstract
Background and Objectives: Chronic abdominal pain (CAP) in children may be a precursor to irritable bowel syndrome (IBS) in adults. The prevalence of abnormal lactulose breath tests (LBT) suggesting small intestinal bacterial overgrowth (SIBO) has been reported as 91% in children with CAP and 35% in healthy controls. In addition, patients with IBS with SIBO who responded to nonabsorbable antibiotic treatment with normalization of LBT reported 75% global improvement in symptoms. The aim of the study was to test whether treatment with a nonabsorbable antibiotic may reduce symptoms in children with CAP.
Methods: Seventy-five children ages 8 to 18 years with CAP based on Rome II criteria were enrolled. Subjects underwent baseline LBT and completed symptom-based questionnaires. They were then randomized in a 2:1, double-blind fashion to receive a 10-day course of 550 mg of rifaximin or placebo 3 times per day (t. i.d.). LBT and questionnaires were repeated 2 weeks after treatment.
Results: Forty-nine children received rifaximin and 26 received placebo. There were no differences in demographics between groups. Ninety-four percent who received rifaximin and 92% who received placebo had abnormal baseline LBT, suggesting SIBO (not significant [NS]). There was no significant difference in symptom improvement between groups; however, only 20% of children treated with rifaximin achieved a normalized repeat LBT, demonstrating successful treatment of SIBO.
Conclusions: Similar to adults with IBS, the prevalence of abnormal LBT suggesting SIBO in children with CAP is high; however, treatment with 10 days of rifaximin has low efficacy in normalizing LBT in this group. Additional studies are needed to determine whether a treatment approach with higher efficacy would lead to improvement in children with CAP.
Author Information
* Division of Gastroenterology and Nutrition, Children's Hospital Los Angeles and Keck School of Medicine, University of Southern California, Los Angeles, USA
† Gastroenterology Section, New Mexico VA Health Care System and the University of New Mexico, Albuquerque.
Received 23 April, 2010
Accepted 1 July, 2010
Address correspondence and reprint requests to Brynie Slome Collins, MD, Division of Gastroenterology and Nutrition, Children's Hospital Los Angeles, MS #78, 4650 Sunset Blvd, Los Angeles, CA 90027 (e-mail: bcollins@chla. usc. edu).
The present study was supported by the Saban Research Institute Research Career Development Fellowship Award, Clinical Research Academic Career Development Award, and the CHLA General Clinical Research Center (GCRC) through NIH NCRR GCRC Grant MO1 RR-46. It was also supported, in part, by an unrestricted grant from Salix Pharmaceuticals. Salix played no role in the conception of the hypothesis, experimental design, conduct of the study, data analysis, or preparation of the manuscript.
Dr Lin has IP rights in a related area. Dr Lin is supported by the NIH, the VA, and the Department of Defense.
ClinicalTrials. gov Identifier: NCT00619970.
The authors report no conflicts of interest.
Chronic abdominal pain (CAP) is a frequent and often debilitating childhood complaint. The overwhelming majority of children with CAP have a functional gastrointestinal disorder with symptoms not explained by anatomical or biochemical abnormalities. Although the exact prevalence of CAP is unknown, this diagnosis is responsible for 2% to 4% of all of the pediatric office visits in the United States, (1). with 13% to 19% of American school-age children experiencing weekly abdominal pain (2). Moreover, the abdominal pain and associated symptoms experienced by these children are often so severe that school performance, psychosocial function, and overall quality of life are impaired (3–5) .
Although a unifying pathogenesis has yet to be identified for CAP, several mechanisms have been proposed to explain the symptoms of this condition, including altered intestinal motility (6). abnormal visceral perception (7). and psychological factors (8). Recently, evidence has also pointed to an underlying gut microbial mechanism for CAP (9,10) .
Normally, in humans, the concentration of gut microbes is greatest in the colon, dropping steeply from 10 10–12 organisms/mL in the cecum to 10 5–8 organisms/mL in the proximal ileum and 10 0–4 in the jejunum and duodenum (10). Hydrogen produced by bacterial fermentation is eliminated, in part, by methanogens or sulfate-reducing bacteria that convert hydrogen to methane or hydrogen sulfide (11,12). These microorganisms are competitive because the stool of an individual usually produces high concentrations of either methane or hydrogen sulfide.
When the microbial population native to the large intestine migrates proximally into the small intestine, a shift in the host–gut microbial relationship occurs known as small intestinal bacterial overgrowth (SIBO) (13). In patients with SIBO, abnormal microbial fermentation can occur in the small intestine and may be detected by measuring hydrogen and methane in the exhaled breath after ingestion of a fermentable substrate such as lactulose. This response is the basis for the lactulose breath test (LBT) (14). Because methanogens reside in the large intestine, with their concentration highest in the left colon (15). methane is normally absent from the exhaled breath during a 180-minute LBT.
Similar to patients with CAP, patients with SIBO complain of postprandial bloating, abdominal pain, nausea, vomiting and diarrhea, and constipation, as well as a variety of extraintestinal symptoms such as fatigue. In our recently published study (9). abnormal microbial fermentation suggesting SIBO was found in 91% of patients with CAP compared with 35% in healthy controls. These data are similar to that of Scarpellini et al (16). who found that 65% of children with irritable bowel syndrome (IBS) had SIBO. Abnormal microbial fermentation has also been reported in 78% to 84% of adult patients with IBS compared with 20% in healthy controls (17,18). In addition, in a randomized, double-blind, placebo-controlled trial, patients with IBS who responded to treatment with a nonabsorbable antibiotic, as shown by normalization of the LBT, reported 75% global improvement in symptoms (18). To date, there are no published data on the effect of antibiotic treatment in children with CAP. Therefore, the aim of the present study was to test the hypothesis that treatment of SIBO with a nonabsorbable antibiotic may reduce symptoms in children with CAP.
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