Am Fam Physician. 2010 Oct 1;82(7):836.
Background: Studies have shown that the underlying pathogenesis of Crohn disease may involve microbial penetration of the bowel mucosal barrier; therefore, antibiotic therapy should be beneficial. Nevertheless, current guidelines recommend antibiotic therapy only for sepsis, bacterial overgrowth syndromes, or perianal disease. Feller and colleagues conducted a meta-analysis of all reported clinical trials of long-term antimicrobial therapy for Crohn disease.
The Study: The authors searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials to identify eligible studies. The references of all identified articles were also checked for additional studies. Eligible trials randomly allocated participants to treatment and placebo groups and lasted at least three months. Studies restricted to perianal disease were excluded from the meta-analysis.
Data about the study conduct and outcomes were independently extracted by two researchers. Drugs from the same class were analyzed together (e.g., the antituberculosis agents rifampicin [available as rifampin in the Unites States], isoniazid, and ethambutol).
Results: Of the 43 identified studies, 16 trials involving more than 800 patients met eligibility criteria. The quality of reporting study methods was low, with only four studies adequately describing allocation concealment. Eleven studies involved patients with active disease, and three studies concerned patients with inactive disease. Four studies did not report diagnostic criteria for Crohn disease.
The 13 different treatment regimens studied ranged from single agents to combinations of four different drugs. Antituberculosis drugs and nitroimidazoles were each used in three studies; clarithromycin (Biaxin) and clofazimine were each used in four studies. Three studies incorporated steroid therapy, seven studies allowed steroids if clinically indicated, and four studies excluded steroid use. The median duration of treatment was six months.
The principal outcome was remission or recurrence of symptoms. The Crohn's Disease Activity Index was used to assess outcomes in 11 studies, and another disease activity index was used in an additional four studies.
The combined odds ratio (OR) from the three studies of 107 patients treated with antituberculosis drugs was 0.58, indicating no benefit. The three studies involving 206 patients treated with nitroimidazoles reported a combined OR of 3.54, indicating benefit.
Similarly, benefit was demonstrated in the four studies involving 322 patients treated with clofazimine (OR = 2.86) and one trial using ciprofloxacin (Cipro; OR = 11.3). Little evidence of benefit was found in a trial of rifaximin (Xifaxan) or a trial of sulfadoxine/pyrimethamine. Results from the four studies using clarithromycin (287 patients) were heterogeneous and were excluded from the meta-analysis. The estimated number needed to treat to keep one additional patient in remission was 3.4 for nitroimidazoles and 4.2 for clofazimine.
Conclusion: The authors conclude that patients with Crohn disease receive substantial benefit from three or more months of therapy with nitroimidazoles and clofazimine. The authors found one trial that supported ciprofloxacin use. Little evidence of benefit was found for clarithromycin or classic antituberculosis drugs.
ANNE D. WALLING, MD
Feller M, et al. Long-term antibiotic treatment for Crohn's disease: systematic review and meta-analysis of placebo-controlled trials. Clin Infect Dis. February 15, 2010;50(4):473–480.
Copyright © 2010 by the American Academy of Family Physicians.
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