Antibiotics and Probiotics in Inflammatory Bowel Disease: Why, When, and How

Cosimo Prantera; Maria Lia Scribano

Disclosures

Curr Opin Gastroenterol. 2009;25(4):329-333. 

In This Article

Antibiotics and Crohn's Disease

In the last years several groups have reported the presence of E. coli in Crohn's disease ileal and colonic tissue.[14,15]E. coli with adherent-invasive properties (AIEC) found in these specimens is able to colonize the intestinal mucosa and to invade and replicate within macrophages, inducing the secretion of a large quantity of TNF.[16] Clarithromycin, a macrolide wide-spectrum antibiotic, can penetrate into macrophages and can be effective in eradicating the bacteria.

The only trial performed last year in active Crohn's disease has compared clarithromycin 1g against placebo, administered for 3 months to 41 patients with Crohn's disease with CDAI over 200 points and high concentration of C-reactive protein (CRP).[17•] There was no difference in the remission or response rate at 3 months between the antibiotic and placebo and the study was stopped. It is possible that clarithromycin, given its mediocre activity against E. coli, is not the best antibiotic to treat Crohn's disease flares, assuming that AIEC is really implicated.

Maintenance of Crohn's disease remission induced by surgery or by drugs is a key goal for a gastroenterologist. His/her job is to increase the time until reappearance of lesions and to reduce their severity without inducing significant side effects. A patient's compliance with the prescribed drug is crucial. It is well established that surgery in Crohn's disease is followed by a high 1-year endoscopic recurrence and that bacteria are strongly suspected to be implicated in the recurrence of the lesions. Antianaerobic bacterial drugs, such as metro and ornidazole, have been shown to reduce the severity of endoscopic recurrence after Crohn's disease surgery, but their long-term use is burdened by a low compliance because of an elevated number of side effects. A randomized, placebo-controlled study employed a 3-month course of metro in combination with a 1-year of azathioprine to reduce the 1-year endoscopic recurrence in 81 operated patients with high risk of recurrence.[18••] This strategy reduces the period of metro use utilizing it as bridge therapy, given the slow action of azathioprine. Four patients were withdrawn because of side effects; in three of them side effects probably due to metro occurred in the first 3 months. The difference in recurrence rates between metro and azathioprine and metro and placebo was statistically significant, 55 vs. 78%, respectively, thus offering the prospect of a biologically plausible therapy with limited side effects. This strategy combines the approach of reducing the anaerobic bacteria with the down-regulation of immune response. In fact, a recent study on Crohn's disease paediatric patients reported that a subset of such patients with antibodies against microbial antigens was more susceptible to complications.[19•]

The most significant reason for antibiotic treatment failure is the emergence of side effects, particularly important in long-term treatment. The interest of clinicians has been recently moved towards the nonabsorbable antibiotic rifaximin which, due to its high safety profile, is suitable for long-term treatment. Rifaximin, active against anaerobic bacteria and E. coli, has been approved for the treatment of traveller's diarrhoea. In 2008 two case reports described the response to rifaximin in six patients with Crohn's disease.[20,21] In one of these articles the clinical remission obtained in three newly diagnosed ileal Crohn's disease patients was confirmed also by a capsule endoscopy mucosal improvement.[20] The doses employed varied from 600 to 800 mg daily for a period of 3 weeks to over 6 months. A previous rifaximin-controlled trial had shown that 800 mg given twice daily for 3 months in patients with elevated CRP provided the best result.[22]

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