Review: Primary Treatment of Crohn’s Disease with Antibiotics
In 2011, Dr. William Chamberlin, Prof. Thomas Borody and Dr. Jordana Campbell collaborated on a meta-analysis of the published Medline studies from 1976 to 2011 which discussed Crohn’s disease patients treated with antibiotic combination therapy. The article, Primary Treatment of Crohn’s Disease: Combined Antibiotics Taking Center Stage, gives unbiased data on the effectiveness of antibiotic use in Crohn’s disease. For those of you who are short on time or find this type of technical reading difficult, we have attempted to summarize the key points.
Why use antibiotics to treat Crohn’s disease? Increasing evidence points to gut bacteria as playing a key role in Crohn’s disease. The authors propose two hypotheses: Either antibiotics affect the gut flora in a beneficial manner that is unknown or antibiotics are ridding the body of a specific pathogen that the body cannot effective fight due to predetermined genetic defects.
The earliest studies indicated that metronidazole (Flagyl) had a beneficial effect on Crohn’s disease. In the 1990’s, Ciprofloxacin (Cipro) was use in combination with metronidazole or alone in multiple trials, and was also found to have a significantly beneficial effect on Crohn’s disease. In 2005, Dr. Shafran began to trial the broad-spectrum antibiotic Rifaximin on Crohn’s disease patients. The patients receiving only Rifaximin therapy had a higher remission rate (70%) than those receiving Rifaximin plus steroids (58%).
In the 1980’s, researchers noticed that patients who were receiving tuberculosis therapy showed an improvement of their Crohn’s disease symptoms as well. The initial report of one unlucky patient stricken with both tuberculosis and Crohn’s disease showed remission of Crohn’s disease when treated with an anti-tuberculosis therapy of isoniazid, rifamipicin, pyrazinaminde and ethambuterol for 9 months. Dapsone, another anti-tuberculosis therapy, was trialed with some success that proved limited when larger studies were completed.
The pathogen, Mycobacterium avium paratuberculosis (MAP) had been a candidate as the causative agent of Crohn’s disease for years because it caused a very similar illness in cattle called Johne’s disease. It was also a relative of Mycobacterium tuberculosis. MAP is an intracellular bacteria, meaning it hides inside the immune cells, and only an antibiotic with intracellular effectiveness would be effective against it. Generally, tuberculosis therapies are not effective against intracellular bacteria.
Eventually, researchers began looking at other antimycobacterial agents that had intracellular effectiveness and began having more success when the leprosy drug, clofazimine, was added to the cocktail. (Leprosy is caused by Mycobacterium leprae.) Clarithromycin was trialed as well, and although results were initially positive, treatment with clarithromycin alone (a macrolide) was likely to result in antibiotic resistance. The combination of three or four medications containing macrolides with intracellular effectiveness for more than 6 months was found to minimize antibiotic resistance.
The table below summarizes the Anti-MAP trials with success rates ranging from 44% to 89% remission rates.
The Selby study, while meeting the criteria of a large-scale, randomized trial studying the effectiveness of the Anti-MAP therapy, was widely criticized. One issue was that the data was not analyzed based on the standard Intention-to Treat (ITT) method. Once the data was analyzed using an ITT method, the remission rates were significantly higher in the Anti-MAP group than for those taking the placebo. Another problem with the trial was that the doses of antibiotics were below optimal levels, and by the author’s own admission, the clofazimine capsule failed to rupture, and patients did not receive the medication. Despite these short-comings, the Anti-MAP therapy in the Selby trial actually performed better than the anti-TNF medications currently used for Crohn’s disease. See a comparison of Anti-MAP vs. Anti-TNF therapies on the Treatment of Crohn’s via Anti-MAP Therapy page.
The authors conclude with some case reports from their own practices using Anti-MAP therapy, and discuss the genes which predispose people to Crohn’s disease by inhibiting the immune system’s ability to attack and clear intracellular infections such as MAP. Some of these genes are NOD2, IRGM and ATG16L1. In summary, the authors state that properly chosen antibiotics are beneficial in treating Crohn’s disease.