JAC Advance Access published online on February 3, 2009
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkp003
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Original research |
Identification and molecular characterization of triple- and quadruple-resistant Helicobacter pylori clinical isolates in Germany
1 National Reference Centre for Helicobacter pylori, Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital Freiburg, Hermann-Herder-Str. 11, 79104 Freiburg, Germany 2 Institute of Biostatistics, Austrian Agency for Health and Food Safety, Graz, Austria
Received 12 August 2008; returned 29 September 2008; revised 14 November 2008; accepted 3 January 2009
* Corresponding author. Present address: Department of Immunology and Molecular Pathology, Royal Free Hospital and University College Medical School, Pond Street, London NW3 2QG, UK. Tel: +44-20-7794-0500 ext. 34932; Fax: +44-20-7433-1943; E-mail: e.glocker{at}medsch.ucl.ac.uk
Objectives: The aim of this study was to estimate the frequency of triple- and quadruple-resistant Helicobacter pylori isolated in Germany, to characterize those isolates molecular genetically and to identify risk factors for the development of multiresistance.
Methods: Antimicrobial susceptibility to metronidazole, clarithromycin, amoxicillin, tetracycline, ciprofloxacin/levofloxacin and rifampicin in 1118 clinical isolates obtained between July 2006 and December 2007 was tested by the Etest® method. For patients harbouring triple- or quadruple-resistant strains (n = 169), data on prior eradication therapies and underlying diseases were collected and evaluated. A select number of quadruple- and triple-resistant strains were examined for resistance-mediating mutations in their 23S rRNA, 16S rRNA, gyrA and rpoB genes, respectively.
Results: From 1118 clinical isolates, 13.4% (n = 150) showed phenotypic resistance to metronidazole, clarithromycin and quinolones and 0.9% (n = 10) to metronidazole, clarithromycin and rifampicin; one isolate exhibited resistance to clarithromycin, quinolones and rifampicin. In eight isolates (0.7%), we detected phenotypic quadruple resistance to metronidazole, clarithromycin, quinolones and rifampicin or tetracycline. Triple- and quadruple-resistant strains harboured resistance-associated mutations in their 23S rRNA, 16S rRNA, gyrA or rpoB genes and were nearly exclusively isolated from patients who had already been unsuccessfully treated on multiple occasions.
Conclusions: We show that more than 15% of H. pylori strains isolated from routine samples in the German National Reference Centre are resistant to three or more antimicrobials and identified prior unsuccessful eradication therapies as a key factor for the development of multiresistance. Our data emphasize the need for further comprehensive surveillance studies monitoring the role of treatment regimens in antimicrobial resistance in H. pylori.
Key Words: multiresistance , mutations , gyrA , 23S rRNA , rpoB , 16S rRNA , treatment failure
These authors contributed equally to this work.