Two-year-outcomes analysis of Crohn's disease treated with rifabutin and macrolide antibiotics

Abstract

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 randomized controlled trial.

Fusobacterium nucleatum Infection of Colonic Cells Stimulates MUC2 Mucin and Tumor Necrosis Factor Alpha

“…Mucosal homeostasis is intricately linked with the community of microbial residents of the gut, the so-called gut microbiota. Both animal (22,33,42) and clinical (11,14,39) studies support the view that changes in the density and composition of the intestinal microbiota (dysbiosis) lead to initiation and perpetuation of IBD, although it is not known whether this imbalance is driven by functional alteration of the commensal gut microbial population or introduction of pathogenic species.…”

Pathogenesis of Crohn’s disease: Bug or no bug

“…The authors who favor MAP as causative agent remark that most IBD antibiotic regimens are not fully effective for MAP and that good MAP treatments need to include macrolides, should include triple or quadruple therapies, or should be sustained for very long periods of time, as is done in tuberculosis treatment. Several long-term regimens have been performed, showing initial improvement, with steroid weaning, but concluding that the benefit is not sustained [58,59] . A two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for CD was used in a study performed in Australia, in which significant improvement up to week 16 was observed, although subsequent follow-up results were not conclusive.…”

Body Traffic: Ecology, Genetics, and Immunity in Inflammatory Bowel Disease

“…In CD, Mycobacterium avium subspecies paratuberculosis (MAP) is a recurrent candidate for several reasons: its association with epidemic bovine colitis, the presence of anti-MAP antibodies and MAP sequence by polymerase chain reaction (PCR) CD patients, and some reports that antimycobacterial drugs ameliorate disease (143)(144)(145)(146). However, other groups were unable to detect these microorganisms, and the prevalence of disease-associated anti-MAP antibodies is variable.…”