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Antimicrobial Agents and Chemotherapy, July 2002, p. 2244-2248, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2244-2248.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Pharmacodynamic Effects of Nitroimidazoles Alone and in Combination with Clarithromycin on Helicobacter pylori

Margareta Svensson,1,2 Magnus Ström,2 Maud Nilsson,1 Mikael Sörberg,3 and Lennart E. Nilsson1*

Divisions of Clinical Microbiology,1 Gastroenterology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, SE-581 85 Linköping,2 Infectious Diseases Unit, Department of Medicine, Karolinska Hospital, S-171 76 Stockholm, Sweden3

Received 15 December 2000/ Returned for modification 2 June 2001/ Accepted 29 March 2002

Pharmacodynamic studies of Helicobacter pylori exposed to metronidazole and tinidazole alone and in combination with clarithromycin were performed by bioluminescence assay of intracellular ATP. The pharmacodynamic parameter control-related effective regrowth time (CERT) was used. CERT is defined as the time required for the resumption of logarithmic growth and a return of the level of growth to the preexposure inoculum in the test culture minus the corresponding time in the control culture. CERT measures the combined effects of the initial level of killing and postantibiotic effect. The incubation times and drug concentrations were chosen according to their half-lives and their clinically achievable concentrations. The study shows that the parameter CERT is useful for the testing of antibiotic combinations. The CERTs induced by clarithromycin, metronidazole, and tinidazole alone and in the combinations tested were concentration dependent, with no maximum response, indicating that the use of high doses may be preferable. The combinations with the highest concentrations induced synergistic effects and prevented regrowth. The use of tinidazole in combination with clarithromycin proved to give the longest CERTs, indicating that this is the most effective combination.


* Corresponding author. Mailing address: Division of Clinical Microbiology, Department of Molecular and Clinical Medicine, Faculty of Health Sciences, SE-581 85 Linköping, Sweden. Phone: 46 13 222098. Fax: 46 13 224596. E-mail: len{at}imk.liu.se.


Antimicrobial Agents and Chemotherapy, July 2002, p. 2244-2248, Vol. 46, No. 7
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.7.2244-2248.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.