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Title: Clinical and laboratory studies of the bacterial pathogenesis and management of pouchitis
Author: McLaughlin, Simon D.
ISNI:       0000 0004 2688 5943
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2010
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20-50% of patients develop pouchitis following restorative proctocolectomy for ulcerative colitis (UC). Pre-pouch ileitis (PPI) also develops in some of these patients. Bacteria are implicated in the pathogenesis of pouchitis and antibiotics are the mainstay of treatment. Studies were performed to examine the role of bacteria in the pathogenesis of this disease and to develop new treatment. Further studies examined the prevalence and implications of PPI and the efficacy and complications associated with maintenance antibiotic therapy. 16s rRNA sequencing demonstrated an increase in Proteobacteria and a reduction in Bacteroidetes in the UC compared with the familial adenomatous polyposis (FAP) cohort, but only limited differences between the UC non-pouchitis and pouchitis groups. We were unable to identify an individual species or phylotype specifically associated with pouchitis. Treatment with elemental diet produced a symptomatic improvement in 71% of chronic pouchitis patients but none entered clinical remission. Patients with PPI were identified, the prevalence, symptoms and short term outcomes of this group were studied. PPI was identified in 5.7% of patients with UC. All patients had associated pouchitis but not all were symptomatic. PPI was not associated with reclassification to Crohn’s disease. A subgroup of patients with symptomatic pre-pouch ileitis were treated with combination antibiotic therapy and 86% entered remission. Faecal samples from patients with antibiotic resistant pouchitis were grown on agar and sensitivity patterns identified. Following guided antibiotic therapy 80% of patients entered remission. Stool analysis also identified the presence of extended spectrum beta-lactamase (ESBL) resistant coliforms in 35% of patients with chronic pouchitis. Not all were symptomatic. PPI was associated with an increased risk of ESBL. Patients treated with maintenance antibiotic therapy were identified. Pre-pouch ileitis was associated with an increased risk of relapse. Reported side effects were rare and treatment was associated with an improved quality of life.
Supervisor: Nicholls, John ; Petrovska, Liljana ; Clark, Sue ; Tekkis, Paris Sponsor: St Mark's Hospital Foundation
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral