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Antimicrobial Agents and Chemotherapy, July 2003, p. 2249-2255, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2249-2255.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Gastric Transitional Zones, Areas where Helicobacter Treatment Fails: Results of a Treatment Trial Using the Sydney Strain Mouse Model

Sander J. O. Veldhuyzen van Zanten,1* Tassia Kolesnikow,2 Vincent Leung,3 Jani L. O'Rourke,2 and Adrian Lee2

Queen Elizabeth II Health Sciences Center, Dalhousie University, Halifax, Nova Scotia, Canada,1 University of New South Wales, School of Biotechnology and Biomolecular Sciences, Sydney, Australia,2 Department of Medicine & Geriatrics, United Christian Hospital, Kwun Tong, Hong Kong3

Received 7 October 2002/ Returned for modification 27 January 2003/ Accepted 17 April 2003

Current combination therapies cure Helicobacter pylori infection in 75 to 85% of cases. However, many treatment failures are not explained by antibiotic resistance. Our goal was to explore treatment failures under in vivo conditions by using the H. pylori Sydney strain (SS1) mouse model. Mice infected with H. pylori (SS1) were treated with monotherapies or combination therapies used in human trials. Bacterial levels and distribution of organisms within the stomach were assessed 24 h after treatment to determine clearance and location of treatment failures and 29 days after treatment to determine cure rates. Except for treatment with metronidazole, mono- and dual therapies did not cure infection but resulted in decreases in bacterial levels and differences in distribution within the stomach. In cases of treatment failure when clarithromycin was used, omeprazole and dual therapy with omeprazole and amoxicillin resulted in organisms being cleared from the antrum, but organisms remained in the antrum-body transitional zone. The triple therapies of OMC and bismuth subcitrate, metronidazole, and tetracycline were successful in eradicating infection. Except for metronidazole monotherapy and triple therapy with OAC, there was good correlation between the Sydney strain mouse model and humans with respect to the success of antimicrobial therapy. The antrum-body transitional zone was identified as a sanctuary site in treatment failure. This could result from antimicrobial agents not functioning effectively at this site or bacteria in this location expressing products that protect them against antimicrobial agents. This is the first demonstration of a possible sanctuary site as a reason for failure of therapy.


* Corresponding author. Mailing address: Victoria General Hospital Site, Room 928, South Wing, Centennial Bldg., Halifax, Nova Scotia B3H 2Y9, Canada. Phone: (902) 473-2397. Fax: (902) 473-4406. E-mail: Zanten{at}dal.ca.


Antimicrobial Agents and Chemotherapy, July 2003, p. 2249-2255, Vol. 47, No. 7
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.7.2249-2255.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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