Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption
- Francis Megraud1,2,
- Samuel Coenen3,
- Ann Versporten3,
- Manfred Kist4,
- Manuel Lopez-Brea5,
- Alexander M Hirschl6,
- Leif P Andersen7,
- Herman Goossens3,
- Youri Glupczynski8,
- on behalf of the Study Group participants*
- 1INSERM U853, Bordeaux, France
- 2Laboratoire de Bactériologie, Centre National de Référence des Campylobacter et Helicobacter, Université de Bordeaux, Bordeaux, France
- 3Laboratory of Medical Microbiology, Vaccine and Infectious Disease Institute (VAXINFECTIO), University of Antwerp, Antwerp, Belgium
- 4National Reference Centre for Helicobacter pylori, Institute of Medical Microbiology and Hygiene, University Hospital Freiburg, Freiburg, Germany
- 5Instituto de Investigación Sanitaria del Hospital La Princesa, Hospital de la Princesa, Madrid, Spain
- 6Department of Laboratory Medicine, Division of Clinical Microbiology, Medical University Vienna, Vienna, Austria
- 7Rigshospitalet, Department of Infection Control, Copenhagen University Hospital, Copenhagen, Denmark
- 8Laboratoire de Bactériologie, Centre National de Référence des Helicobacter pylori, Université Catholique de Louvain, CHU Mont-Godinne, Yvoir, Belgium
- Correspondence to Dr Professor Francis Megraud, Laboratoire de Bactériologie – CHU, Pellegrin Place Amelie Raba-Leon, F-33076 Bordeaux cedex, France; Professor Youri Glupczynski, Laboratoire de Bactériologie, Cliniques Universitaires UCL de Mont-Godinne 1, Avenue Docteur Gaston Therasse, B-5530 Yvoir, Belgium;
Contributors FM and YG designed the multicentre study protocol which was amended by all members of the Steering Committee of the European Multicentre study on antibiotic susceptibility of Helicobacter pylori (LPA, AMH, MK, MLB). FM was the coordinator of the Steering Committee, he was responsible for the analysis and interpretation of the data and he prepared the initial draft of the manuscript. YG and FM equally contributed to the analysis of data, the preparation and subsequent revisions of the manuscript. SC, AV and HG collected and provided data on outpatient antibiotic use in Europe from the ESAC project data base, and SC provided statistical advice and analysis; the members of the Steering Committee critically reviewed the analysis of the data and the manuscript and all authors contributed to the final version of the manuscript.
- Revised 28 March 2012
- Accepted 30 March 2012
- Published Online First 12 May 2012
Objective Resistance to antibiotics is the major cause of treatment failure of Helicobacter pylori infection. A study was conducted to assess prospectively the antibacterial resistance rates of H pylori in Europe and to study the link between outpatient antibiotic use and resistance levels in different countries.
Design Primary antibiotic resistance rates of H pylori were determined from April 2008 to June 2009 in 18 European countries. Data on yearly and cumulative use over several years of systemic antibacterial agents in ambulatory care for the period 2001–8 were expressed in Defined Daily Doses (DDD) per 1000 inhabitants per day. The fit of models and the degree of ecological association between antibiotic use and resistance data were assessed using generalised linear mixed models.
Results Of 2204 patients included, H pylori resistance rates for adults were 17.5% for clarithromycin, 14.1% for levofloxacin and 34.9% for metronidazole, and were significantly higher for clarithromycin and levofloxacin in Western/Central and Southern Europe (>20%) than in Northern European countries (<10%). Model fit improved for each additional year of antibiotic use accumulated, but the best fit was obtained for 2005. A significant association was found between outpatient quinolone use and the proportion of levofloxacin resistance (p=0.0013) and between the use of long-acting macrolides only and clarithromycin resistance (p=0.036).
Conclusion In many countries the high rate of clarithromycin resistance no longer allows its empirical use in standard anti-H pylori regimens. The knowledge of outpatient antibiotic consumption may provide a simple tool to predict the susceptibility of H pylori to quinolones and to macrolides and to adapt the treatment strategies.
Funding The authors acknowledge the support of AB Biodisk, now AB bioMerieux, who provided the Etests for the study, and Axcan Pharma, now Aptalis Pharma, who helped us for the logistic part of the study.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.