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Intestinal bacteria play an important role in the pathogenesis of Crohn’s disease, which occurs at sites with the highest concentrations of bacteria. Adherent invasive Escherichia coli associate with the ileal mucosa in Crohn’s disease,1 and E coli, Bacteroides, and fusiform bacteria are associated with early disease recurrence after surgical resection.2 The incidence of clinical recurrence is approximately 50% at three years, with the risk higher in smokers than non-smokers. Endoscopic recurrence occurs in 73–90% of patients one year after surgery,3 and clinical disease correlates reasonably well with the endoscopic score.4 Current postoperative prophylaxis therapies are unsatisfactory. Mesalazine 3 g daily, 6-mercaptopurine 50 mg daily, and azathioprine 2 mg/kg daily are only slightly more effective than placebo.5 Antimicrobial agents have demonstrated efficacy in postoperative prophylaxis reducing the recurrence at the ileocolonic anastomosis. Metronidazole reduced severe endoscopic recurrence at three months and reduced clinical relapse at one year, but was poorly tolerated with significant nausea and vomiting.6 Ornidazole 1 g daily for one year postoperatively reduced severe endoscopic and clinical recurrence at one year but not at two or three years.7 We report a case of severe recurrent ileocolonic disease successfully treated with combination ciprofloxacin and metronidazole.
A 23 year old man with a three month history of abdominal pain and diarrhoea was diagnosed with Crohn’s disease in October 1996 after a small bowel series revealed narrowing and ulceration of the distal 10 cm of the terminal ileum. His symptoms were steroid responsive for two years. Colonoscopy in June 1998 for recurrent abdominal pain showed severe ulceration and stenosis of the ileocaecal valve and with his symptoms unresponsive to corticosteroids he underwent surgical resection of a segment of severe fistulising terminal ileal Crohn’s disease. The remaining small bowel appeared normal. Histopathology confirmed severe active cicatrising Crohn’s disease, with stenosis and gross wall thickening with a cobblestone appearance. He made an uncomplicated recovery and remained well without medication. Follow up colonoscopy in April 1999 demonstrated minor recurrent Crohn’s disease affecting one third of the ileocolonic anastomosis. He commenced metronidazole 400 mg daily, and on colonoscopy in March 2000 had severe inflammation and narrowing of the entire circumference of the ileocolonic anastomosis preventing ileal intubation. Ciprofloxacin 750 mg/day was added to the metronidazole. Colonoscopy in August 2001 showed superficial ulceration of less than one third of the anastomosis, minimal narrowing, and a normal neoterminal ileum and colon. He continued metronidazole 400 mg daily and ciprofloxacin 750 mg alternate daily until January 2003 when colonoscopy demonstrated a normal anastomosis, neoterminal ileum, and colon. The patient remained on ciprofloxacin 750 mg twice weekly and metronidazole was ceased. Colonoscopy 12 months later showed very minor ulceration affecting 5 mm of the anastomosis, no significant narrowing, and a normal neoterminal ileum.
Ciprofloxacin, a fluoroquinolone, is effective against intestinal aerobic Gram negative bacteria such as E coli, Shigella, Salmonella, and clostridial species. It is well tolerated even with prolonged use8 but can cause hepatotoxicity and tendon fragility. In Crohn’s disease trials, ciprofloxacin was superior to placebo in decreasing the Crohn’s disease activity index in one study9 but ciprofloxacin and metronidazole in combination with budesonide showed no benefit over placebo and budesonide. However, subgroup analysis by disease site revealed a clear improvement in the antibiotic treated group with Crohn’s colitis.10
To our knowledge, this is the first report of antibacterial therapy producing complete endoscopic resolution of severe postoperative recurrence at the ileocolonic anastomosis. This patient has remained well, and has not developed any untoward side effects. We believe a controlled trial should be performed to test whether low dose ciprofloxacin alone or in combination can prevent recurrence of Crohn’s disease at the ileocolonic anastomosis.
Conflict of interest: None declared.
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