a Department of Clinical Microbiology and Infection Control, b Department of Gastroenterology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands
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Abstract |
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Introduction |
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Materials and methods |
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A total of 231 clinical isolates of H. pylori were collected from 21 participating laboratories in The Netherlands. Each participating laboratory collected 10-15 consecutive clinical isolates. All strains were cultured from gastric biopsies of patients with peptic ulcer disease who underwent a diagnostic endoscopy. These strains were collected between September 1997 and February 1998. Isolates were frozen in 20 vol% glycerol in Brain Heart Infusion broth (Difco Laboratories, Detroit, MI, USA) transferred to our laboratory and subcultured on to Columbia agar (Becton Dickinson, Cockeysville, MD, USA) supplemented with 10% lysed horse blood (Bio Trading, Mijdrecht, The Netherlands), and H. pylori selective supplement (Oxoid, Basingstoke, UK), referred to as Dent plates. Plates were incubated for 72 h at 37°C in an atmosphere of O 2/CO 2/N 2 (5:10:85). Identification was performed by means of Gram's stain, catalase, oxidase, and urea hydrolysis.
Determination of MIC
Inocula were prepared from a H. pylori culture grown on Dent plates. MICs were determined by Etest (AB Biodisk, Solna, Sweden) essentially as described by Glupczynski et al., 12 on Columbia agar supplemented with 10% lysed horse blood plates inoculated with approximately 2 x 10 8 cfu in 20 µL of 0.9% NaCl.
Consumption of macrolide antibiotics and metronidazole
Data on the consumption of macrolide antibiotics and metronidazole were obtained from the `Stichting Farmaceutische Kengetallen The Hague, The Netherlands'.
Interregional differences in antibiotic consumption and resistance rates
To obtain an insight into potential interregional differences in antibiotic consumption and resistance rates, we divided The Netherlands into three regions, namely West, North-East and South regions. Patients whose strains were studied were classified into one of these three regions based on their place of residence.
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Results |
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Discussion |
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Two out of a total of four clarithromycin-resistant strains in this study were also resistant to metronidazole. This number is high, since in the total bacterial population tested only one out of five (20%) strains was metronidazole resistant. High prevalence rates for double resistance may be the result of combination therapy as indicated by the findings of Buckley et al. 14 If the infecting strain is already resistant to metronidazole, the patient can be treated effectively with clarithromycin monotherapy.
Metronidazole use in The Netherlands has increased steadily over the last 4 years. We found an overall metronidazole resistance rate of 21.2%. This is 3% higher than in 1994/1995. 7 With a desired cure rate of >90%, the observed metronidazole resistance may preclude the use of this drug for empirical treatment. Our metronidazole resistance rates compare with the 32% metronidazole resistance reported by van der Wouden et al. 8 In the present study five out of 11 strains originating from the same area as those studied by van der Wouden et al. were resistant to metronidazole, and although the numbers are small this could indicate that there are regional variations in the prevalence of metronidazole resistance in The Netherlands. Metronidazole consumption in this area was similar to elsewhere in the country and so the increased incidence of resistance may be due to poor patient compliance, inadequate dosing regimens, or clonal distribution of a metronidazole- resistant strain.
Another interesting finding of our study was that in spite of the fact that trovafloxacin has not yet been introduced on to the Dutch market the resistance to trovafloxacin is as high as 4.7%. Most likely the observed resistance results from induction by related quinolones. The role of trovafloxacin in the treatment of H. pylori infection needs further investigation.
In conclusion, although resistance to amoxycillin and tetracycline was not observed in this study, the resistance rates for clarithromycin and metronidazole in H. pylori in The Netherlands have increased over the last 3 years. We recommend susceptibility testing before starting therapy with metronidazole.
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Acknowledgments |
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Notes |
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References |
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2
.
Walsh, J. H. & Peterson, W. L. (1995). The treatment of Helicobacter pylori infection in the management of peptic ulcer disease. New England Journal of Medicine
333
, 984
91.
3 . Debets-Ossenkopp, Y. J., Sparrius, M., Kusters, J. G., Kolkman, J. J. & Vandenbroucke-Grauls, C. M. J. E. (1996). Mechanism of clarithromycin resistance in clinical isolates of Helicobacter pylori. FEMS Microbiology Letters 142 , 37 42.[ISI][Medline]
4 . Megraud, F., Occhialini, A. & Doermann, H. P. (1997). Resistance of Helicobacter pylori to macrolides and nitroimidazole compounds. The current situation. Journal of Physiology and Pharmacology 48, Suppl. 4 , 25 38.[Medline]
5 . Xia, H. X., Keane, C. T. & O'Morain, C. A. (1996). A 5-year survey of metronidazole and clarithromycin resistance in clinical isolates of Helicobacter pylori. Gut 39, Suppl. 2 , A6 .
6 . Lopez-Brea, M., Domingo, D., Sanchez, I. & Alarcon, T. (1997). Evolution of resistance to metronidazole and clarithromycin in Helicobacter pylori clinical isolates from Spain. Journal of Antimicrobial Chemotherapy 40 , 279 81.[Abstract]
7 . van Zwet, A. A., de Boer, W. A., Schneeberger, P. M., Weel, J., Jansz, A. R. & Thijs, J. C. (1996). Prevalence of primary Helicobacter pylori resistance to metronidazole and clarithromycin in The Netherlands. European Journal of Clinical Microbiology and Infectious Diseases 15 , 861 4.[ISI][Medline]
8 . van der Wouden, E. J., van Zwet, A. A., Vosmaer, G. D. C., Oom, J. A. J., de Jong, A. & Kleibeuker, J. H. (1997). Rapid increase in the prevalence of metronidazole-resistant Helicobacter pylori in The Netherlands. Emerging Infectious Diseases3 ,385 9.[ISI][Medline]
9 . Midolo, P. D., Korman, M. G., Turnidge, J. D. & Lambert, J. R. (1996). Helicobacter pylori resistance to tetracycline. Lancet 347 , 1194 5.[ISI][Medline]
10 . Polzer, R. J., Potchoiba, M. J., Renouf, D. N., West, M. & Liston, T. E. (1995). Distribution of [14C] CP-99,219 into gastric tissue of Long-Evans rats and Swiss-Webster mice following intravenous administration. In Abstracts of the Seventh European Congress of Clinical Microbiology and Infectious Diseases, Vienna, 26- 30 March 1995, Abstract 745 p.144.
11 . Girard, A. E., Cimochowski, C. R., Girard, D., Gootz, T. D. & Brighty, K. E. (1995). In vitro and in vivo activities of CP-99,219 against Helicobacter. Abstracts of the Seventh European Congress of Clinical Microbiology and Infectious Diseases, Vienna, 26-30 March 1995, Abstract 739 p.143.
12 . Glupczynski, Y., Labbé, M., Hansen, W., Crokaert, F. & Yourassowsky, E. (1991). Evaluation of the Etest for quantitative antimicrobial susceptibility testing of Helicobacter pylori. Journal of Clinical Microbiology 29 ,2072 5.[ISI][Medline]
13 . Versalovic, J., Shortridge, D., Kibler, K., Griffy, M. V., Beyer, J., Flamm, R. K. et al. (1996). Mutations in 23S rRNA are associated with clarithromycin resistance in Helicobacter pylori. Antimicrobial Agents and Chemotherapy 40 , 477 80.
14 . Buckley, M. J., Xia, H. X., Hyde, D. M., Keane, C. T. & O'Morain, C. A. (1997). Metronidazole resistance reduces efficacy of triple therapy and leads to secondary clarithromycin resistance. Digestive Diseases and Sciences 42 ,2111 5.[ISI][Medline]
Received 28 July 1998; returned 12 October 1998; revised 28 October 1998; accepted 18 November 1998