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Antimicrobial Agents and Chemotherapy, May 1998, p. 1222-1228, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Risk of Development of In Vitro Resistance to Amoxicillin, Clarithromycin, and Metronidazole in Helicobacter pylori

Mikael Sörberg,1,* Håkan Hanberger,2 Maud Nilsson,3 Anders Björkman,1 and Lennart E. Nilsson3

Department of Infectious Diseases, Danderyd Hospital, S-182 88 Danderyd,1 and Infectious Diseases2 and Department of Clinical Microbiology,3 University Hospital, S-581 85 Linköping, Sweden

Received 11 August 1997/Returned for modification 3 December 1997/Accepted 12 February 1998

We have studied initial killing, morphological alterations, the frequency of occurrence, and the selective growth of resistant subpopulations of Helicobacter pylori during exposure to amoxicillin, clarithromycin, or metronidazole by bioluminescence assay of intracellular ATP levels, microscopy, and a viable count assay. We found an induction of spheroplasts and a decrease in intracellular ATP levels after 21 h of exposure to high concentrations of amoxicillin. During clarithromycin exposure the onset of a decrease in intracellular ATP levels started after prolonged incubation, and with the highest concentration of clarithromycin an induction of coccoid forms was seen after 68 h. Metronidazole exposure resulted in the strongest initial decrease in intracellular ATP levels, and coccoid forms were seen after 21 h of exposure to high concentrations of metronidazole. Amoxicillin caused a low-level increase in resistant subpopulations, which indicates a need for surveillance of the amoxicillin susceptibility of H. pylori in order to detect decreasing susceptibility. No increase in the numbers of resistant subpopulations was demonstrated during clarithromycin exposure. Metronidazole selected resistant subpopulations, which caused high-level resistance in H. pylori.

* Corresponding author. Mailing address: Department of Infectious Diseases, Danderyd Hospital, S-182 88 Danderyd, Sweden. Phone: 468 655 6025. Fax: 468 755 12 37. E-mail: Mikael.Sorberg{at}kids.ki.se.

Antimicrobial Agents and Chemotherapy, May 1998, p. 1222-1228, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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