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• Severe recurrent Crohn's disease of ileo-colonic anastomosis and antimicrobial (anti-Mycobacterial)
  Thomas J Borody
  Published on: 3 February 2006

• Published on: 3 February 2006

  Severe recurrent Crohn's disease of ileo-colonic anastomosis and antimicrobial (anti-Mycobacterial)

  • Thomas J Borody, Gastroenterologist
  • Other Contributors:
    • Leonid Heifets

  Dear Editor,

  Elliott et al. (Gut 2005; 54: 1818-19) present an interesting and clinically useful finding of successful treatment of a patient with severe Crohn’s disease and circumferential narrowing of the ileo-colonic anastomosis treated with 750 mg ciprofloxacin plus 400mg metronidazole daily for almost three years, resulting in complete healing and opening up of the stenosed anastomosis.

  The author...

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  Dear Editor,

  Elliott et al. (Gut 2005; 54: 1818-19) present an interesting and clinically useful finding of successful treatment of a patient with severe Crohn’s disease and circumferential narrowing of the ileo-colonic anastomosis treated with 750 mg ciprofloxacin plus 400mg metronidazole daily for almost three years, resulting in complete healing and opening up of the stenosed anastomosis.

  The authors list a number of bacterial species known to be susceptible to these antibiotics. However, they have omitted perhaps the most important potential pathogen, Mycobacterium avium ss paratuberculosis (MAP), the leading candidate causal agent of Crohn’s disease[1,2]. It is well known that ciprofloxacin exhibits marked activity against Mycobacterium avium[3]. It is also known that metronidazole can be bactericidal against dormant M. tuberculosis in anaerobic conditions[4]. Although no such data are yet available concerning other mycobacteria, the role of metronidazole in affecting M. avium ss. paratuberculosis cannot be excluded, when these bacteria persisted in anaerobic conditions. It is indeed very unlikely that the success of metronidazole/ciprofloxacin combination had much to do with luminal flora bacteria, but more likely, it treated indolent tissue MAP, which may explain the need for prolonged therapy. We can be even more certain that luminal flora was not the only target of these antibiotics, especially ciprofloxacin, because more than 10 prolonged trials of various combinations of anti-tuberculosis antibiotics were inactive against MAP, were active against luminal flora bacteria, yet still failed to improve the outcome of Crohn’s disease[5]. On the other hand, in our experience[6] with specific anti-MAP treatment, we have reported five patients whose terminal ileal strictures returned to normal, an indication that prolonged, targeted anti-microbial therapy is necessary to inhibit tissue MAP and its consequent inflammation and oedema[6].

  In retrospect it was difficult to accept that a chronic infection with a previously poorly-known organism could cause such widespread gastro -duodenal disease. In the pre-Helicobacter era bismuth was thought to “chelate with protein at an acid pH...may stimulate release of mucus”[7,8] when actually it was acting via a completely different mechanism, inhibiting growth of Helicobacter pylori. Similarly, in this case report one could initially postulate that metronidazole+ciprofloxacin exerts its effect by inhibiting local bowel flora. On closer examination it becomes more plausible that data presented in this case report supports involvement of MAP in causation of inflammation, oedema and stenosis in Crohn’s disease and that prolonged anti-MAP treatment can progressively reduce inflammation.

  References

  1. Bull TJ, McMinn EJ, Sidi-Boumedine K, et al. Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn’s disease. J Clin Microbiol 2003; 41: 2915-23.

  2. Naser SA, Ghobrial G, Romero C, Valentine JF. Culture of Mycobacterium avium subspecies paratuberculosis from the blood of patients with Crohn’s disease. Lancet 2004; 364: 1039-44.

  3. Heifets LB, Lindholm-Levy PJ. Bacteriostatic and bactericidal activity of ciprofloxacin and ofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex. Tubercle 1987; 68: 267-76.

  4. Wayne LG, Sramek HA. Metronidazole is bactericidal to dormant cells of Mycobacterium tuberculosis. Antimicrob Agents Chemother 1994; 38: 2054-8.

  5. Greenstein RJ. Is Crohn’s disease caused by a mycobacterium? Comparisons with leprosy, tuberculosis and Johne’s disease. Lancet Infect Dis 2003; 3: 507-14.

  6. Borody TJ, Leis S, Warren EF, Surace R. Treatment of severe Crohn’s disease using antimycobacterial triple therapy – approaching a cure? Dig Liver Dis 2002; 34: 9-12.

  7. Salmon P, Brown P, Williams R, Read A. Evaluation of colloidal bismuth (TDB) in treatment of duodenal ulcers employing endoscopic selection and followup. Gut 1974; 15: 189-93

  8. Jagu J. Bismuth in medicine. Bull Bismuth Inst 1971; 2:1.

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  Conflict of Interest:
  None declared.

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