JAC Advance Access originally published online on February 3, 2009
Journal of Antimicrobial Chemotherapy 2009 63(4):648-653; 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.
Keywords: multiresistance , mutations , gyrA , 23S rRNA , rpoB , 16S rRNA , treatment failure
These authors contributed equally to this work.