title: Treatment of severe Crohn's disease using antimycobacterial triple therapy--approaching a cure?
abstract: BACKGROUND
  Mycobacterium avium subspecies paratuberculosis is probably the best candidate for a microbial cause of Crohn's disease although arguments to the contrary can be equally convincing. Growing evidence suggests that prolonged antimycobacterial combination therapy can improve Crohn's disease in some patients.
  
  
  OBJECTIVE
  To report long-term observations in patients with severe Crohn's disease treated with triple macrolide-based antimycobacterial therapy.
  
  
  METHODS
  A series of 12 patients (7 male, 5 female; aged 15-42 years) with severe, obstructive or penetrating Crohn's disease were recruited.
  
  
  METHODS
  Patients failing maximal therapy were commenced prospectively on a combination of rifabutin (450 mg/d), clarithromycin (750 mg/d) and clofazimine (2 mg/kg/d). Progress was monitored through colonoscopy, histology, clinical response and Harvey-Bradshaw activity index.
  
  
  RESULTS
  Follow-up data were available for up to 54 months of therapy Six out of 12 patients experienced a full response to the antiMycobacterium avium subspecies paratuberculosis combination achieving complete clinical, colonoscopic and histologic remission of Crohn's disease. Four of these patients were able to cease treatment after 24-46 months, 3 of whom remained in total remission without treatment for up to 26 months and one patient relapsed after six months off treatment. A partial response to the anti-Mycobacterium avium subspecies paratuberculosis combination was seen in 2 patients showing complete clinical remission with mild histologic inflammation. Return to normal of terminal ileal strictures occurred in 5 patients. Harvey-Bradshaw activity index in patients showing a full or partial response to therapy fell from an initial 13.4 +/- 1. 91 to 0. 5 +/- 0. 47 [n = 8, p < 0. 001) after 52-54 months.
  
  
  CONCLUSIONS
  Reversal of severe Crohn's disease has been achieved in 6/12 patients using prolonged combination anti-Mycobacterium avium subspecies paratuberculosis therapy alone. Three patients remain in long-term remission with no detectable Crohn's disease off all therapy These results support a causal role for Mycobacterium avium subspecies paratuberculosis in Crohn's disease while also suggesting that a cure may become possible.
authors.affiliation: Centre for Digestive Diseases, Sydney, Australia. tborody@zip.com.au
authors.forename: T J
authors.initials: TJ
authors.lastname: Borody
authors.forename: S
authors.initials: S
authors.lastname: Leis
authors.forename: E F
authors.initials: EF
authors.lastname: Warren
authors.forename: R
authors.initials: R
authors.lastname: Surace
mesh_terms: D000293:Adolescent; D000328:Adult; D017291:Clarithromycin / Q000627:therapeutic use; D002991:Clofazimine / Q000627:therapeutic use; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D009164:Mycobacterium Infections / Q000188:drug therapy*; D016927:Mycobacterium avium subsp. paratuberculosis / Q000302:isolation & purification*; D010865:Pilot Projects; D011446:Prospective Studies; D017828:Rifabutin / Q000627:therapeutic use; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D017828:Rifabutin; D002991:Clofazimine; D017291:Clarithromycin