Sulphadoxine-pyrimethamine therapy in Crohn's disease. Randomized controlled trial of clarithromycin and ethambutol in the treatment of Crohn’s disease Controlled trial of anti-tuberculous chemotherapy for two years in Crohn's disease. Two-year-outcomes analysis of Crohn's disease treated with rifabutin and macrolide antibiotics. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn's disease. Controlled trial of rifampicin and ethambutol in Crohn's disease. Antimycobacterial therapy in Crohn's disease: results of a controlled, double-blind trial with a multiple antibiotic regimen. Is Rifaximin Effective in Maintaining Remission in Crohn's Disease? Open label trial of clarithromycin therapy in Japanese patients with Crohn's disease. Open label trial of oral clarithromycin in active Crohn’s disease Controlled trial of antimycobacterial therapy in Crohn's disease An antibiotic regimen for the treatment of active Crohn's disease: a randomized, controlled clinical trial of metronidazole plus ciprofloxacin. Addition of Metronidazole to Azathioprine for the Prevention of Postoperative Recurrence of Crohn’s Disease: A Randomized, Double-Blind, Placebo-Controlled Trial Ciprofloxacin for the Prevention of Postoperative Recurrence in Patients with Crohn's Disease: A Randomized, Double-blind, Placebo-controlled Pilot Study
A double-blind controlled clinical trial has shown no benefit from the use of sulphadoxine-pyrimethamine over a 12-month period in chronically active Crohn ’s disease A mycobacterial infection may be the cause of Crohn ’s disease in some patients . Measurement of intestinal permeability may identify Crohn ’s disease patients with a high likelihood of relapse and may quantify the severity of intestinal injury One hundred and thirty patients with active symptoms of Crohn 's disease were treated in a double blind r and omised controlled trial with rifampicin , isoniazid , and ethambutol , or identical placebos for up to two years . All other treatment considered necessary was continued . Analyses were based on 126 patients , 63 in each treatment group . Thirty seven in the active and 30 in the placebo group had previous surgical procedures . There was no difference in concomitant treatment between the two groups . Thirty in the active and 46 in the placebo groups were taking corticosteroids at entry to the trial . Forty eight of 63 patients in the active and 49 of 63 in the placebo group , completed at least 12 months ' therapy . Reasons for early withdrawal included pregnancy , adverse reaction , and failure to comply . There was no significant difference in the mean number of months completed between the two groups . Nineteen adverse reactions were recorded for 17 patients in the active group compared with three reactions in patients on placebo . All of the nine patients withdrawn early because of adverse reactions were in the active group . Fifteen patients on active treatment and 14 on placebo had surgery during the trial with no difference in the type of surgery required between the groups . Radiological assessment s based on 98 patients at the end of the trial showed no significant differences between groups in changes of extent of disease . More patients developed strictures on placebo compared with active treatment but without a statistically significant difference . No differences were found between groups for the total prednisolone dose or the number of days on which prednisolone dose was 10 mg or above . Serial measurements of body weight and Crohn 's disease activity index ( CDAI ) together with blood values for albumin , haemoglobin , white cell count , and platelets showed no consistent different differences between groups . There were occasional significant differences for some of these values between groups , which were not sustained . The trail provides little evidence of tangible benefit from the trail treatment Fifty-two patients with severe Crohn 's disease were enrolled in this study . Six ( 11.5 % ) were intolerant of the medication and had to be excluded . The remaining 46 patients were treated with rifabutin in combination with a macrolide antibiotic ( clarithromycin or azithromycin ) .  Patients were treated for a mean of 18.7 ( range 6 - 35 ) months and followed up for 25.1 ( range 7 - 41 ) months . Of the 19 patients who were steroid dependent at the start of this study , only two continued to require steroids when treatment was established . A reduction in the Harvey-Bradshaw Crohn 's disease activity index occurred after 6 months ' treatment ( P = 0.004 , paired Wilcoxon test ) and was maintained at 24 months ( P < 0.001 ) . An improvement in inflammatory parameters was observed as measured by a reduction in erythrocyte sedimentation rate ( P = 0.009 ) and C-reactive protein ( P = 0.03 ) at 18 months compared with pretreatment levels , and an increase in serum albumin at 12 months ( P = 0.04 ) . When subsets of the study population were analysed , patients with pan-intestinal disease achieved better remission at 2 years than did those with less extensive involvement ( P = 0.04 , Mann-Whitney U-test ) . No difference in treatment response by age , disease duration , the presence of granulomas on histology , or the occurrence of drug-induced side-effects , was observed . These data suggest that treatment with rifabutin and clarithromycin or azithromycin may result in a substantial clinical improvement in Crohn 's disease and justify the conduct of a r and omized controlled trial BACKGROUND & AIMS Mycobacterium avium subspecies paratuberculosis has been proposed as a cause of Crohn 's disease . We report a prospect i ve , parallel , placebo-controlled , double-blind , r and omized trial of 2 years of clarithromycin , rifabutin , and clofazimine in active Crohn 's disease , with a further year of follow-up . METHODS Two hundred thirteen patients were r and omized to clarithromycin 750 mg/day , rifabutin 450 mg/day , clofazimine 50 mg/day or placebo  , in addition to a 16-week tapering course of prednisolone . Those in remission ( Crohn 's Disease Activity Index < or=150 ) at week 16 continued their study medications in the maintenance phase of the trial . Primary end points were the proportion of patients experiencing at least 1 relapse at 12 , 24 , and 36 months . RESULTS At week 16 , there were significantly more subjects in remission in the antibiotic arm ( 66 % ) than the placebo arm ( 50 % ; P=.02 ) . Of 122 subjects entering the maintenance phase , 39 % taking antibiotics experienced at least 1 relapse between weeks 16 and 52 , compared with 56 % taking placebo ( P=.054 ) . At week 104 , the figures were 26 % and 43 % , respectively ( P=.14 ) . During the following year , 59 % of the antibiotic group and 50 % of the placebo group relapsed ( P=.54 ) . CONCLUSIONS Using combination antibiotic therapy with clarithromycin , rifabutin , and clofazimine for up to 2 years , we did not find evidence of a sustained benefit . This finding does not support a significant role for Mycobacterium avium subspecies paratuberculosis in the pathogenesis of Crohn 's disease in the majority of patients . Short-term improvement was seen when this combination was added to corticosteroids , most likely because of nonspecific antibacterial effects We pursued the possibility that Mycobacterium kansasii might be an aetiological agent in Crohn 's disease by carrying out a trial of treatment with antimycobacterial drugs .  Twenty seven patients with Crohn 's disease took part in a two year r and omised double blind , crossover , controlled trial of rifampicin plus ethambutol against placebo .  Fourteen patients completed the trial ; four required an operation ; five were withdrawn as poor compliers , and four because of adverse effects . There was no significant difference in response to the active drugs compared with placebo when expressed in terms of a Crohn 's disease activity index or any clinical indicator of disease activity . There was no suggestion that any subgroup of patients - for example , different regions of bowel affected or previous operation - were favourably affected by the drugs . There was no consistent pattern of change in  prednisolone requirements although eight patients on long term sulphasalazine had a significant reduction in their plasma sulphapyridine concentrations during the active treatment period . A significant reduction in total white blood count and an increase in plasma ALT were seen during active therapy . The results of the study do not suggest that rifampicin and ethambutol have a role to play in the treatment of Crohn 's disease UNLABELLED Several recent reports have suggested an association of atypical mycobacteria with Crohn 's disease . OBJECTIVES The goal of this double-blind , placebo-controlled trial was to determine the efficacy of treatment with antimycobacterial drugs in maintaining clinical remission and in reducing active inflammatory lesions . METHODS Forty patients ( 15 male ) with refractory , steroid-dependent Crohn 's disease were r and omized to receive 2 months of tapering steroids plus either a 9-month regimen of ethambutol , clofazimine , dapsone and 1-day dose only of rifampicin ( n = 22 ) , or identical placebo . RESULTS Three patients ( two on active drug ) were unable to discontinue steroids , and one patient on active drug was withdrawn for side effects during the first 2 months . Three of the remaining 19 patients on active drug relapsed during the study period , compared with 11 of 17 on placebo ( log likelihood ratio = 4.6 ; p = 0.03 ) . Another patient was withdrawn in remission at 5 months for anemia related to dapsone . Nine patients whose disease relapsed or persisted on placebo were crossed over to active drug ; five achieved sustained remission , two failed , and two were withdrawn for side effects . Substantial endoscopic or radiologic healing did not occur . CONCLUSION This study suggests that the treatment regimen with rifampicin , ethambutol , clofazimine , and dapsone is effective in relief of symptoms and maintenance of remission in some Crohn 's disease patients Background : Recent studies indicate that persistent intestinal inflammation in patients with Crohn 's disease ( CD ) might be caused by abnormal intestinal microbiota . This hypothesis may suggest a beneficial effect of antibiotics in CD therapy . So far , guidelines do not recommend antibiotics except in the treatment of complicated CD , and there are few studies on the effects of rifaximin in these patients . Methods : Between December 2011 and December 2012 , we performed a blinded r and omized trial in 168 patients with a previous history of moderately active CD concerning the efficacy of rifaximin .  All the patients had previously achieved remission with st and ard therapy ( prednisone/budesonide ) . Data from patients receiving 800 mg of rifaximin ( 83 patients ) twice a day for 12 weeks were compared with those from patients who received placebo ( 83 patients ) . The primary endpoint was maintaining remission during the follow-up . Results : All the patients ( 100 % ; 83/83 ) on 800 mg of rifaximin were in remission after 12 weeks of treatment in comparison with 84 % ( 70/83 ) of the placebo group . This significant difference was also persistent at the 24-week follow-up [ 78 % ( 65/83 ) vs. 41 % ( 34/83 ) , respectively ] . The last evaluation performed at 48 weeks revealed disease activity in 45 % ( 38/83 ) of the patients of the rifaximin group , i.e. a significant decrease compared with the placebo group [ 75 % ( 63 of 83 ) ] . Conclusions : Remission previously obtained with st and ard treatment can be sustained in patients with moderately active CD after the administration of 800 mg of rifaximin BACKGROUND AND AIM The pathogenesis of Crohn 's disease is unclear , but many studies suggest that luminal bacteria play an important role in chronic intestinal inflammation in patients with this condition . Clarithromycin is a macrolide antibiotic with immunomodulatory activity . The aim of this study was to evaluate the effect of clarithromycin therapy in Japanese patients with Crohn 's disease . METHODS Fourteen patients with active Crohn 's disease ( 12 with ileocolonic , one with colonic , one with small bowel type ) were treated with oral clarithromycin 200 mg twice daily for 4 weeks . Patients who showed a clinical response within 4 weeks continued the therapy for up to 24 weeks . Four patients also received azathioprine . Clinical activity was assessed with the Crohn 's Disease Activity Index ( CDAI ) at entry and at 4 , 12 , and 24 weeks after starting clarithromycin . RESULTS The mean CDAI score at entry was 343.5 . Within 4 weeks , eight ( 57.1 % ) of the 14 patients showed clinical improvement , and five ( 35.7 % ) of the eight patients achieved remission . All of those eight patients continued clarithromycin therapy after 4 weeks , and six ( 42.9 % ) were in clinical remission at 12 weeks . Of the 14 total patients , four ( 28.6 % ) continued clarithromycin for more than 24 weeks , and have remained in remission . Patients who received azathioprine concomitantly had a better response to clarithromycin therapy . No severe side-effects were observed during the study period . CONCLUSIONS This open label study showed encouraging results of clarithromycin therapy in Japanese patients with active Crohn 's disease Crohn ’s disease seems likely to be due in some way to bacteria . Clarithromycin is a broad spectrum macrolide antibiotic with good penetration into macrophages and may be effective in eradicating the organisms that are presumed to be at the centre of the granulomatous reaction in Crohn ’s disease In order to study the effect of clofazimine , a powerful antimycobacterial and antiinflammatory agent , 49 patients with active Crohn 's disease were r and omized to either corticosteroids plus clofazimine 100 mg daily ( N=25 ) or to steroids and matching placebo ( N=24 ) . A total of 28 patients ( 58 % ) went into disease remission ( clofazimine 16 , placebo 12;P = NS ) with a fall in disease activity score from 10.5±4.4 to 3.3±3.5 . Patients were treated for a further eight months with clofazimine or placebo and 18 of 28 maintained their remission and completed the study ( clofazimine 12 , placebo 6;P = NS ) . Side effects were minor and consisted of skin rash and increased pigmentation  . Clofazimine as a solitary antimycobacterial agent appears ineffective in inducing remission in Crohn 's disease but may have a role in either disease maintenance or combination chemotherapy OBJECTIVES Bacteria in the gut lumen may play a role in the etiology and /or the symptoms of Crohn 's disease ( CD ) . Although various antibacterial drugs have been employed in clinical practice , few controlled trials have been conducted , and those had conflicting results . The aim of this study was to investigate the efficacy and the safety of a combination of metronidazole and ciprofloxacin , compared with methylprednisolone , in treating 41 consecutive patients with active CD . METHODS Eligible patients , 13 men and 28 women , mean age 38 yr , were r and omly allocated to receive , for 12 wk , ciprofloxacin 500 mg twice daily plus metronidazole 250 mg four times daily or methylprednisolone 0.7-l mg/kg/day , with variable tapering to 40 mg , followed by tapering of 4 mg weekly . RESULTS Ten of the 22 antibiotic patients ( 45.5 % ) and 12 of the 19 steroid patients ( 63 % ) obtained clinical remission ( Crohn 's Disease Activity Index < or = 150 ) at the end of the 12-wk study ( p = NS ) . Five patients on antibiotics ( 22.7 % ) and five patients on steroids ( 26.3 % ) were considered treatment failures because of deterioration or persistent symptoms . Six patients receiving antibiotics ( 27.3 % ) and two on steroids ( 10.6 % ) were withdrawn from the trial because of side effects . One patient on antibiotics was not compliant . CONCLUSIONS metronidazole and ciprofloxacin could be an alternative to steroids in treating the acute phase of CD Background : Endoscopic recurrence occurs in up to 80 % of patients with Crohn ’s disease 1 year after intestinal resection .  Imidazole antibiotics , thiopurines , and particularly their combination have proven efficacy in preventing endoscopic recurrence . The aim of the study was to compare the efficacy of the addition of metronidazole ( for 3 months after the surgical treatment ) to azathioprine for the prevention of postsurgical endoscopic recurrence . Methods : A pilot study was made of 50 patients with Crohn ’s disease undergoing intestinal resection with ileocolic anastomosis and treated with 2 to 2.5 mg/kg of azathioprine per day for 1 year . The patients were r and omized to receive additional 15 to 20 mg/kg of metronidazole per day or placebo for the first 3 months ( n = 25 per arm ) . Endoscopic assessment was performed 6 and 12 months after the surgical resection . The primary end point was the prevention of endoscopic recurrence as defined by a Rutgeerts score of < 2 at 6 months . The initial sample size had an 80 % statistical power in detecting an absolute risk reduction of ≥30 % . Results : Endoscopic recurrence occurred in 28 % and 44 % of the patients at 6 months ( P = 0.19 ) and in 36 % and 56 % ( P = 0.15 ) at 12 months in the metronidazole and placebo groups , respectively . No statistically significant differences were found between the treatment groups regarding severe endoscopic recurrence ( Rutgeerts score ≥ 3 ) at 6 and 12 months . Likewise , there were no differences in the rate of adverse events between the treatment groups . Conclusions : The addition of metronidazole to azathioprine did not significantly reduce the risk of endoscopic recurrence  beyond azathioprine alone in this study but does not worsen its safety profile Background : The commensal bacterial flora plays a critical role in the postoperative recurrence of Crohn 's disease ( CD ) . We conducted a r and omized , double-blind , placebo-controlled 6-month pilot trial of ciprofloxacin for the prevention of endoscopic recurrence in patients with CD who underwent surgery . Methods : Thirty-three patients with CD , who had undergone surgery with ileocolonic anastomosis within the previous 2 weeks , were r and omized to treatment with ciprofloxacin ( 500 mg twice daily ) or placebo tablets for 6 months . Endpoints were endoscopic recurrence at 6 months and safety and tolerability of long-term ciprofloxacin therapy . Results : Thirty-three patients were r and omized ; 14 patients discontinued the study early . Significant endoscopic recurrence was observed in 3 of 9 patients ( 33 % ) in the ciprofloxacin group and 5 of 10 patients ( 50 % ) in the placebo group at 6 months after surgery ( P < 0.578 ) . The intention-to-treat analysis demonstrated endoscopic recurrence in 11 of 17 patients ( 65 % ) in the ciprofloxacin group and 11 of 16 patients ( 69 % ) in the placebo group at month 6 ( P < 0.805 ) . Thirty-six adverse events occurred in 19 of 33 patients ( 58 % ) . Possible drug-associated adverse events occurred significantly more often in the ciprofloxacin group ( P < 0.043 ) , leading to study drug discontinuation in 24 % ( 4 of 17 ) and 6 % of patients ( 1 of 16 ) in the ciprofloxacin and placebo groups , respectively ( P < 0.166 ) . Conclusions : In this pilot study , ciprofloxacin was not more effective than placebo for the prevention of postoperative recurrence in patients with CD . Long-term ciprofloxacin therapy is limited by drug-associated side effects . Future studies in postoperative prevention of CD should evaluate antibiotic approaches with a more favorable safety profile
BACKGROUND There have been a number of studies with conflicting results which have examined the effect of anti-tuberculous therapy in Crohn 's disease .
A meta- analysis was performed to evaluate the use of anti-tuberculous therapy for the maintenance of remission in Crohn 's disease .
OBJECTIVES To evaluate the effects of anti-tuberculous therapy for the maintenance of remission in patients with Crohn 's disease .