Ciprofloxacin and probiotic Escherichia coli Nissle add-on treatment in active ulcerative colitis: A double-blind randomized placebo controlled clinical trial
Andreas Munk PetersenHengameh MirsepasiSofie Ingdam HalkjærEsben Munk MortensenInge Nordgaard-LassenKaren A. Krogfelt
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Abstract:
Background and aim: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The probiotic bacterium Escherichia coli Nissle 1917 (EcN) has been used to maintain and induce clinical remission in UC. Our aim was to test the effect of Ciprofloxacin and/or orally administered EcN as add-on to conventional therapies in patients with active UC.Keywords:
Pouchitis
A 26-year-old woman with ulcerative colitis treated with a proctocolectomy and ileal pouch-to-anal anastomosis developed an erosive and ulcerative pouchitis. Although no ophthalmological manifestations were present before the staged surgical procedures, iritis developed after appearance of the pouchitis. Both conditions subsequently resolved with oral corticosteroids and metronidazole.
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Abstract Both ulcerative colitis and pouchitis are associated with an imbalance in the intestinal microbiota, which may be related to the immune response. The objective was to determine the bacterial composition in pouchitis and ulcerative colitis in order to explore the underlying pathogenesis. Microbiome was profiled and evaluated by 16S ribosomal DNA gene sequencing in stool samples of 37 patients with ulcerative colitis, 15 patients with normal ulcerative colitis-pouch, 15 patients with ulcerative colitis-pouchitis and 18 healthy volunteers, PICRUSt and PICRUSt2 were performed to analyze the function of dominant bacteria. In our Chinese cohort, with aggravation of ulcerative colitis, intestinal microorganisms were characterized by a gradual decreased in diversity and numbers of butyrate-producing bacteria and Bacteroides. Besides, in addition to the decrease of probiotics, the bloom of Escherichia-Shigella and Ruminococcus_gnavus was observed in pouchitis which related to multiple infection pathways according to KEEG pathway analysis. Our results showed that pouchitis and ulcerative colitis differ in their intestinal microbial structures and metabolic pathways, but the reasons need to be further explored.
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BACKGROUND: Pouchitis is the most common long-term complication after restorative total proctocolectomy and IPAA for ulcerative colitis. OBJECTIVE: We examined the incidence, clinical aspects, and long-term outcome of patients with idiopathic pouchitis. DESIGN: This study was a retrospective review of medical records. PATIENTS: Included in the study were 284 patients with ulcerative colitis who underwent a total proctocolectomy and IPAA. MAIN OUTCOME MEASURES: We evaluated the cumulative risk and long-term outcome of pouchitis including the duration of disease, pattern of relapse, and responsiveness to antibiotic therapy. RESULTS: Sixty-four patients developed idiopathic pouchitis. The cumulative risk was 10.7% at 1 year, 17.2% at 2 years, 24.0% at 5 years, and 38.2% at 10 years. At their first pouchitis episode, 45 patients had acute pouchitis, 19 patients had chronic pouchitis, and all patients received antibiotic therapy with oral ciprofloxacin and/or metronidazole. The efficacy of the therapy was 96.6% initially. Forty-five patients had antibiotic-responsive pouchitis, 17 patients had antibiotic-dependent pouchitis, and 2 patients had antibiotic-refractory pouchitis at their first episode. Whereas 20 of 45 patients (44.4%) with initially acute pouchitis experienced 2 or more relapses, 16 of 19 patients (84.2%) with initially chronic pouchitis had 2 or more relapses. After taking into account the relapses, the number of patients with antibiotic-responsive pouchitis decreased from 45 to 40, the number with antibiotic-dependent pouchitis increased from 17 to 20, and the number with antibiotic-refractory pouchitis increased from 2 to 4. Among the 4 patients with antibiotic-refractory pouchitis, 3 patients had Clostridium difficile-associated pouchitis. LIMITATIONS: This study was retrospective. CONCLUSION: The patients with chronic pouchitis at the first episode tend to have a higher incidence of relapse. In some patients, the responsiveness to antibiotic therapy changes during follow-up. When patients with pouchitis do not respond to standard antibiotic therapy, then the occurrence of C difficile infection should be considered.
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Objective: To determine levels of soluble forms of the cell adhesion molecules (CAM), ICAM-1, E-Selectin and VCAM-1 in relation to prevalence, treatment and disease activity in inflammatory bowel disease. Patients and methods: Plasma was obtained from patients with ulcerative colitis (n=49), patients with ulcerative colitis who had undergone restorative proctocolectomy (n=32, eight of whom had a clinical pouchitis), Crohn's disease patients (n=34) and 24 healthy controls. Results: Plasma soluble ICAM-1 levels [medians (ranges in ng/ml)] were significantly higher in patients with active ulcerative colitis [270 (90–510)], pouchitis [415 (310–670)] and active Crohn's disease [305 (200–630)]than in those with inactive ulcerative colitis [225 (140–425), P=0.031], non-inflamed ileoanal pouch [260 (140–380), P=0.0004] and inactive Crohn's disease [245 (90–520), P=0.045], respectively, and controls. The soluble E-Selectin levels were also significantly higher in patients with active ulcerative colitis [55 (40–140)], pouchitis [90 (45–145)], and active Crohn's disease [78 (30–115)] than in those with inactive ulcerative colitis [45 (20–80, P=0.003], non-inflamed ileoanal pouch [45 (20–90), P=0.001] and inactive Crohn's disease [48 (25–90, P=0.020], respectively, and controls. Conclusions: The present study suggests that increased levels of soluble ICAM-1 and soluble E-Selectin occur during active inflammatory bowel disease and pouchitis, which may be used as sensitive markers of continuing inflammation.
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The incidence and characteristics of reservoir inflammation after restorative proctocolectomy for ulcerative colitis were studied in a series of 179 patients. The median follow up time was 27 months (range 6-80). Pouchitis occurred in 36 patients (20%) and nine of these (5%) developed a chronic, persisting pouchitis. There were no pouch failures as a result of pouchitis and no significant adverse effect on longterm functional outcome. The overall cumulative risk to develop pouchitis four years after surgery was 23%. The risk of pouchitis is unpredictable on clinical grounds except that there were significantly less patients with left sided colitis in the group who subsequently developed pouchitis. Morphological and histochemical studies showed a greater degree of colonic metaplasia in the pouch mucosa in patients with pouchitis and patients with a chronic pouchitis had the highest degree of changes. The results support the view that pouchitis is a novel manifestation of inflammatory bowel disease in ileal mucosa that has changed slowly to a colon like mucosa.
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