Antibiotic Treatment of Crohn's Disease
Background: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients.
Aim To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease.
Methods We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.).
Results Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05).
Conclusions Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d.
A large set of experimental and clinical data suggest that Crohn's disease (CD) is the consequence of an abnormal genetically determined response of the immune system to the intestinal flora. This hypothesis justifies a therapeutic role for antibiotics. Metronidazole and ciprofloxacin are widely employed in clinical practice for treating perianal disease and Crohn's acute phases, especially when septic symptoms are present, and when colon is involved, even though clear evidence supporting their use is not available. In fact, controlled studies with antibiotics have produced uncertain results. Side effects of metronidazole and ciprofloxacin, however, remain of concern. Apart from short-term intolerance in around 50% of treated patients (nausea, metallic taste and reaction to alcohol), polyneuropathy, secondary to metronidazole, limits the long-term use. Ciprofloxacin is better tolerated in the short term, but is associated with tendonitis and Achilles tendon rupture, especially with concomitant steroids. In a large series, long-term side effects of metronidazole and ciprofloxacin caused treatment interruption in over 20% of cases and a reduced compliance in over 30% of patients.
Rifaximin, a rifamycin derivative, has negligible intestinal absorption –<1% of the oral dose is excreted in the urine – conferring on it an excellent safety profile. Rifaximin inhibits bacterial RNA and therefore protein synthesis by blocking the enzymatic activity of bacterial DNA-dependent RNA polymerase. Its large antimicrobial spectrum covers gram-positive and -negative bacteria, including aerobes and anaerobes. In particular, rifaximin is active against bacteroides and Escherichia coli, two bacteria frequently found in the intestinal mucosa of CD patients.
Rifaximin has been successfully employed in traveller's diarrhoea. Moreover, an open study has recently reported that rifaximin, given at the dose of 200 mg/die t.i.d., induced clinical remission in 59% of 29 CD patients at 16 weeks.
A new gastroresistant formulation of rifaximin (rifaximin EIR) has been developed for the therapy of CD: rifaximin gastroresistant granules are coated with 'methacrylic acid-ethyl acrylate co-polymer' designed to by-pass the stomach and dissolve in the duodenum-jejunum, concentrating the active medication in the small intestine.
This was a multicentre, double blind, randomized, placebo-controlled study in which two doses of rifaximin gastroresistant granules, 800 mg o.d., and 800 mg b.d., given for 12 weeks, were compared with placebo in order to ascertain effectiveness and tolerability in the treatment of mild-to-moderate active CD. This exploratory trial evaluated the difference in efficacy between once and twice/daily oral administrations, and provided data for the sample size calculation required for a larger trial.
Background: Clinicians often employ antibiotics in Crohn's disease. Rifaximin is active against bacteria frequently found in the intestinal mucosa of Crohn's disease patients.
Aim To evaluate the difference in efficacy between once and twice/daily oral administration of rifaximin and placebo in the treatment of active Crohn's disease.
Methods We enrolled 83 patients with mild-to-moderate Crohn's disease and randomized to three treatments for 12 weeks: Group A (rifaximin 800 mg o.d. + placebo), Group B (rifaximin 800 mg b.d.) and Group C (placebo b.d.).
Results Clinical remission was achieved by 52% of Group B, 32% (A) and 33% (C). Clinical response was seen in 67% (B), 48% (A) and 41% (C), without reaching a statistically significant difference. Treatment failures were: 4% (B), 12% (A) and 33% (C), (P = 0.010). Remission and response rates of rifaximin 800 mg b.d. were significantly higher than those of placebo and rifaximin 800 mg o.d. in patients with elevated C reactive protein values (P < 0.05).
Conclusions Rifaximin 800 mg b.d. was superior to placebo in inducing clinical remission of active Crohn's disease. Although this difference was not statistically significant, the number of the failures in the placebo group was significantly higher than those who received rifaximin 800 mg b.d.
A large set of experimental and clinical data suggest that Crohn's disease (CD) is the consequence of an abnormal genetically determined response of the immune system to the intestinal flora. This hypothesis justifies a therapeutic role for antibiotics. Metronidazole and ciprofloxacin are widely employed in clinical practice for treating perianal disease and Crohn's acute phases, especially when septic symptoms are present, and when colon is involved, even though clear evidence supporting their use is not available. In fact, controlled studies with antibiotics have produced uncertain results. Side effects of metronidazole and ciprofloxacin, however, remain of concern. Apart from short-term intolerance in around 50% of treated patients (nausea, metallic taste and reaction to alcohol), polyneuropathy, secondary to metronidazole, limits the long-term use. Ciprofloxacin is better tolerated in the short term, but is associated with tendonitis and Achilles tendon rupture, especially with concomitant steroids. In a large series, long-term side effects of metronidazole and ciprofloxacin caused treatment interruption in over 20% of cases and a reduced compliance in over 30% of patients.
Rifaximin, a rifamycin derivative, has negligible intestinal absorption –<1% of the oral dose is excreted in the urine – conferring on it an excellent safety profile. Rifaximin inhibits bacterial RNA and therefore protein synthesis by blocking the enzymatic activity of bacterial DNA-dependent RNA polymerase. Its large antimicrobial spectrum covers gram-positive and -negative bacteria, including aerobes and anaerobes. In particular, rifaximin is active against bacteroides and Escherichia coli, two bacteria frequently found in the intestinal mucosa of CD patients.
Rifaximin has been successfully employed in traveller's diarrhoea. Moreover, an open study has recently reported that rifaximin, given at the dose of 200 mg/die t.i.d., induced clinical remission in 59% of 29 CD patients at 16 weeks.
A new gastroresistant formulation of rifaximin (rifaximin EIR) has been developed for the therapy of CD: rifaximin gastroresistant granules are coated with 'methacrylic acid-ethyl acrylate co-polymer' designed to by-pass the stomach and dissolve in the duodenum-jejunum, concentrating the active medication in the small intestine.
This was a multicentre, double blind, randomized, placebo-controlled study in which two doses of rifaximin gastroresistant granules, 800 mg o.d., and 800 mg b.d., given for 12 weeks, were compared with placebo in order to ascertain effectiveness and tolerability in the treatment of mild-to-moderate active CD. This exploratory trial evaluated the difference in efficacy between once and twice/daily oral administrations, and provided data for the sample size calculation required for a larger trial.
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