Relevance of the ferret model of Helicobacter-induced gastritis to evaluation of antibacterial therapies.
OBJECTIVE
The goals of the study were 1) to evaluate the efficacy of clinically relevant antibacterial therapies in the ferret model of Helicobacter-induced gastritis and 2) to compare these results to the efficacy achieved clinically in humans.


METHODS
Ferrets were inoculated with H. mustelae, and gastritis was allowed to develop. The double therapy of clarithromycin and omeprazole and the triple therapies of clarithromycin or amoxicillin with metronidazole and omeprazole were administered. Efficacy was evaluated by Helicobacter burden cultured from biopsy samples and by histopathological evaluation of Helicobacter burden and gastric inflammation with pylorus and fundus samples obtained 4 wk after the end of antibacterial therapy.


RESULTS
Clarithromycin-based double and triple therapies significantly reduced Helicobacter burden and decreased gastric inflammation. Clarithromycin-based double therapy was more effective than amoxicillin-based triple therapy. Reduction of the length of clarithromycin therapy from 14 to 7 days decreased efficacy. Antibacterial therapies in the ferret did not produce eradication rates comparable to clinical results, even though the serum concentrations of clarithromycin in ferret were in excess of concentrations used in humans. Relapse of Helicobacter infection after the end of therapy occurred in some cases.


CONCLUSIONS
Although the ferret model of Helicobacter gastric infection underestimated the clinical efficacy of antibacterial treatments in humans, the model was valuable for comparing the relative efficacy of antibacterial therapies.
Alder
J D
JD
Abbott Laboratories, Abbott Park, Illinois, USA.
Ewing
P J
PJ
Mitten
M J
MJ
Oleksijew
A
A
Tanaka
S K
SK
D000658:Amoxicillin / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D000897:Anti-Ulcer Agents / Q000627:therapeutic use; D017291:Clarithromycin / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D005289:Ferrets; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D016998:Helicobacter / Q000145:classification / Q000187:drug effects; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000473:pathology; D008795:Metronidazole / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000627:therapeutic use; D010406:Penicillins / Q000627:therapeutic use; D013997:Time Factors
D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D010406:Penicillins; D008795:Metronidazole; D000658:Amoxicillin; D017291:Clarithromycin; D009853:Omeprazole