In contrast, a combination of ciprofloxacin and metronidazole provided no additional benefit over budesonide, alone, aside from a post-hoc analysis LY317615 for patients with colonic disease[25]. A recent study that compared rifaximin 800 mg bid, 800 mg/placebo and placebo bid failed to show a significant difference between the three groups in clinical response or remission, despite a trend toward benefit with the higher dose[29]. Perianal disease and post-operative maintenance Although antibiotic therapy is frequently used in the treatment of perianal fistulae, there are no randomized controlled trials to support this practice. Data from several small open-label trials conducted in the early 1980s reported the efficacy of metronidazole in healing perianal fistulae[30�C32].

In the post-operative setting a three month course of metronidazole (20 mg/kg per day) decreased the severity of endoscopic lesions at one year (but not at two years) and delayed onset of clinical recurrence[33]. Most recently, ornidazole (1 g/d), started within 10 d of resection and continued for one year, showed significant benefit over placebo in both clinical and endoscopic recurrence rates[34]. The main limitation of long-term metronidazole and ornidazole is peripheral neuropathy. In summary, while antibiotics are used frequently to treat perianal disease, their role in the treatment of active luminal disease and a safe and effective dose schedule in the post-operative setting, remain to be established.

SYSTEMIC STEROIDS Mechanism of action By binding to intracytoplasmic glucocorticoid receptors found in most cell types, glucocorticosteroids activate glucocorticoid-responsive elements (GREs), resulting in a broad spectrum of effects on the immune system including inhibition of the recruitment and proliferation of lymphocytes, monocytes and macrophages, migration of neutrophils to sites of inflammation, and decreased production of soluble inflammatory mediators including cytokines, leukotrienes, and prostaglandins[35]. Natural history The natural history of 171 CD patients diagnosed between 1970 and 1993 has been studied in the Olmsted County, Minnesota population[36]. Of this cohort, only 43% ever required steroids before 1997 and of these, 58% were in complete remission after one month while 26% were in partial remission and 16% had no response. Of those who responded, the one-year outcomes were concerning as only 32% of patients had a prolonged response to corticosteroids, 28% became steroid-dependent and 38% had undergone surgery. These are data that are similar to the reported Danish, Copenhagen County experience[37]. Both exemplify the likelihood of developing Drug_discovery steroid refractory or dependent disease with an accelerated course toward surgery.