RELEVANCE OF THE FERRET MODEL OF HELICOBACTER-INDUCED GASTRITIS TO EVALUATION OF ANTIBACTERIAL THERAPIES

Objectives: The goals of the study were 1) to evaluate the efficacy of clinically relevant antibacterial therapies in the ferret model of He licobacter-induced gastritis and 2) to compare these results to the ef ficacy achieved clinically in humans. Methods: Ferrets were inoculated with H. mustelae, and gastritis was allowed to develop. The double th erapy of clarithromycin and omeprazole and the triple therapies of cla rithromycin or amoxicillin with metronidazole and omeprazole were admi nistered, Efficacy was evaluated by Helicobacter burden cultured from biopsy samples and by histopathological evaluation of Helicobacter bur den and gastric inflammation with pylorus and fundus samples obtained 4 wk after the end of antibacterial therapy. Results: Clarithromycin-b ased double and triple therapies significantly reduced Helicobacter bu rden and decreased gastric inflammation. Clarithromycin-based double t herapy was more effective than amoxicillin-based triple therapy. Reduc tion of the length of clarithromycin therapy from 14 to 7 days decreas ed efficacy. Antibacterial therapies in the ferret did not produce era dication rates comparable to clinical results, even though the serum c oncentrations of clarithromycin in ferret were in excess of concentrat ions used in humans. Relapse of Helicobacter infection after the end o f therapy occurred in some cases. Conclusions: Although the ferret mod el of Helicobacter gastric infection underestimated the clinical effic acy of antibacterial treatments in humans, the model was valuable for comparing the relative efficacy of antibacterial therapies.