Antibiotics for the Treatment of Ulcerative Colitis
Condition: Colitis, Ulcerative
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional

Summary: 
      Ulcerative colitis (UC) is an acute and chronic inflammatory bowel disease, whose cause is
      unknown. However, it is widely accepted that bacteria living in the large bowel are essential
      for the development of the disease. Intuitively, therefore, a logical approach to treatment
      would be to use antibiotics. However, antimicrobial chemotherapy has been unsuccessful in
      managing acute colitis, and has had only limited benefit in long-term treatment. The failure
      of antibiotics in UC arises from the fact that no-one has tried to identify which bacteria
      are involved in causing disease, and equally importantly, nobody has targeted appropriate
      antibiotics to knock out the specific bacteria in question, in a systematic way. Despite
      this, increasing evidence implicates bacteria living on the lining of the bowel being
      involved in UC. Our aim, therefore is to identify bacteria colonizing the mucosal surface in
      the lower large intestine and to determine the antibiotic sensitivities of those the
      investigators believe to be particularly involved in the disease, such as enterococcit,
      peptostreptococci and enterobacteria. Because the investigators have already studied
      resistance to antimicrobial in many mucosal isolate, the investigators plan ot focus on using
      a combination of two antibiotics in this work. A controlled trial will test the benefit of
      using these antibiotics over a period of one month and then the patients will be followed up
      over a six month period. The investigators will be looking for significant long-term
      improvements, and a reduction in drug use following antibiotic therapy.
    

Detailed description: 
      It is now widely acknowledged, as a result of experimental studies over the last 30 years,
      that the mucosal flora of the large bowel are essential to the pathogenesis of ulcerative
      colitis. Whilst treatment with antibiotics, therefore, might seem a logical approach, a
      number of clinical trials have proved disappointing. This is because the principal bacteria
      involved in the inflammatory process have not been identified and their sensitivities to the
      antibacterials determined. Moreover, we are only now beginning to understand the physiology
      of biofilm populations on mucosal surfaces, one property of which is antibiotic resistance.
      Our own studies have show a distinctive bacterial population of the mucosa with UC patients
      with reduced numbers of protective bifidobacteria and increased enterobacteria which we have
      linked to disease activity. Antibiotic resistance to commonly used gut antibiotics is
      widespread in these bacteria.

      Our study, therefore, will commence with multiple biopsies of the distal large bowel mucosa
      being taken in patients with active UC and detailed microbiological characterization of the
      flora using viable counting, chemotaxonomy and molecular approaches. Antibiotic sensitivities
      of the likely pathogens will be determined and dissemination of antibiotic resistance genes
      in the mucosal microbiota followed using real time PCR. Markers of mucosal immune response
      including proinflammatory cytokines and human betea defensins will also be measured. Two
      weeks after initial biopsies, the patient will return to pur research IBD clinic where the
      appropriate combination of antibiotics will be prescribed and these will be taken for one
      month. A further assessment will occur at the end of this period including mucosal biopsies.
      endpoints will include clinical activity index, bowel habit diaries, sigmoidoscopy score,
      mucosal immune markers and routine haematology and biochemical indices. Because of the long
      term effect of antibiotics on the gut mucosa, which can last for many months, the study
      cannot be randomised and therefore, the run in period will be taken as a control period and
      the four weeks on the antibiotic will follow in all patients. The prime endpoint will be
      sigmoidoscopy score and the subjects will be followed up for a further six months after the
      study to look for long term benefits.
    

Intervention name(s): Cefuroxime; Ciprofloxacin; Clarithromycin; Cotrimoxazole; Coamoxiclav; metronidazole; neomycin; rifaximin; Vancomycin; Doxycycline
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention MeSH terms: Metronidazole; Vancomycin; Clarithromycin; Doxycycline; Ciprofloxacin; Rifaximin; Cefuroxime; Neomycin; Trimethoprim, Sulfamethoxazole Drug Combination; Amoxicillin-Potassium Clavulanate Combination
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Antibiotics; Controlled Clinical Trial