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Antibiotic prophylaxis and treatment of reactive arthritis. Lessons from an animal model
Y Zhang1, C Gripenberg-Lerche, K O Söderström
1Department of Medical Microbiology, Turku University, Finland.
Objective:
To study the effect of antibiotic prophylaxis and treatment of reactive arthritis (ReA), using an experimental model.
Methods:
Yersinia enterocolitica O:8, when injected intravenously into Lewis rats, causes a sterile arthritis closely resembling human ReA in 70% of the animals. Arthritis develops in 1-2 weeks; in some of the animals it remains chronic, and exacerbations occur. This model was applied to study the effect of a 7-day treatment with ciprofloxacin, using 2 different dosages (20 or 100 mg/kg/day) and 4 different schedules for initiation of treatment. The effects were evaluated by determining the daily arthritis score, the number of rats developing arthritis, and fecal excretion of Yersinia. In addition, weight gain was monitored. At autopsy (35 or 60 days after inoculation with bacteria), samples were obtained for determination of Yersinia-specific antibodies in the serum. At the same time, samples were collected from mesenteric lymph nodes, lung, spleen, and liver for bacterial cultures, and from the ankle joints for histologic evaluation. In a separate experiment, ciprofloxacin concentrations in samples from serum and mesenteric lymph nodes were analyzed by high performance liquid chromatography.
Results:
A 7-day course with 100 mg/kg/day of ciprofloxacin, started on day 3 after bacterial inoculation, completely prevented the development of ReA and eliminated Yersinia during the 60-day experiment. If a dosage of 20 mg/kg/day was used, development of acute arthritis was prevented, but some of the animals had positive fecal cultures at the end of experiment. If antibiotic treatment was started on day 5, the preventive effect was still observed, but was less pronounced. If the treatment was started at the peak of the development of arthritis, no effect on arthritis was observed.
Conclusion:
These results indicate that if any effect of antibiotic treatment in Yersinia-triggered ReA is to be expected, the treatment must be started early and given in sufficient dosage. However, antibiotic treatment has no effect on fully developed arthritis.