Controversial treatment approach could lead to a cure
Researchers from University of South Florida College of Medicine found a combination of antibiotics to be an effective treatment for Chlamydia-induced reactive arthritis, a major step forward in the management, and possibly cure, of this disease. Results of this study are published in the May issue of Arthritis & Rheumatism, a journal of the American College of Rheumatology.
Reactive arthritis (ReA), also known as Reiter's syndrome, occurs in response to an infection. According to National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the bacterium most often associated with ReA is Chlamydia trachomatis. Respiratory infections with Chlamydia pneumoniae can also trigger ReA, while associated infections in the digestive tract include Salmonella, Shigella, Yersinia, and Campylobacter. ReA symptoms usually last 3 to 12 months, although symptoms can return or develop into a long-term disease. In the past it was thought that only a small percentage of people would experience chronic symptoms of ReA. However, more recent data suggests that as many as 30%-50% of patients could develop a chronic form of the disease. In chronic ReA, symptoms can be severe and difficult to control with treatment, which could lead to joint damage.
The use of long-term antibiotic treatment for patients with ReA is controversial. Several reported studies have indicated that prolonged antimicrobial monotherapy is not efficacious, while other studies suggest there might be a benefit, specifically with early-stage Chlamydia-induced ReA.
The study led by J.D. Carter, M.D., focused on combinations including 2 antibiotics found to have specific effects on the Chlamydia bacteria. The first, rifampin, has excellent tissue penetration, an important weapon against intracellular pathogens such as Chlamydia. Rifampin also has been shown to interfere with chlamydial gene transcription, including the heat-shock proteins (HSPs), which can ultimately lead to the demise of the infected cell. Dr. Carter explains why this is important. "Combining this effect with antibiotics that block chlamydial protein synthesis (e.g., doxycycline or azithromycin) may allow for successful eradication of the cell harboring persistently infecting intracellular organisms. A recent pilot study conducted by our group suggested that prolonged treatment with a combination of doxycycline and rifampin significantly improves symptoms of chronic undifferentiated spondylarthritis (SpA) (with a special focus on Chlamydia) compared with doxycycline alone. The goal of the present study was to further investigate whether a 6-month course of combination antibiotics, one of which is rifampin, is effective in the treatment of patients with chronic Chlamydia-induced ReA."
The 9-month, prospective, double-blind, triple-placebo trial screened a total of 80 subjects, and 42 were enrolled and randomized to treatment. Twelve subjects were randomized to doxycycline and rifampin, 15 were randomized to azithromycin and rifampin, and 15 were randomized to matching oral placebos. The primary end point-an improvement of 20% or more-was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results, demonstrating that compared with placebo, a 6-month course of combination antibiotics resulted in a significantly higher response rate in patients with chronic Chlamydia-induced ReA, although which combination of antibiotics was most effective remained undetermined as the trial wasn't powered to compare the 2 regimens.
Dr. Carter concludes, "The results of this study are encouraging for the management of chronic post-Chlamydia ReA. These data suggest that there is potential for eradication of this persistent infection and that improvement in the clinical sequelae that are the result of these infections can be achieved in a substantial number of patients."
In an Editorial published in this month's issue, Dr. Henning Zeidler agrees. "The study by Carter et al shows impressive effects and, with them, the potential for the eradication of Chlamydia, which would cure Chlamydia-induced ReA."
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