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Influence of metronidazole resistance on efficacy of quadruple therapy for Helicobacter pylori eradication
  1. M C BATESON
  1. Bishop Auckland General Hospital,
  2. Cockton Hill Road,
  3. Bishop Auckland,
  4. County Durham DL14 6AD, UK
    1. R W M VAN DER HULST,
    2. A HOMAN,
    3. G N J TYTGAT
    1. Department of Gastroenterology,
    2. Academic Medical Centre,
    3. Meibergdreef 9,
    4. 1105 AZ Amsterdam,
    5. The Netherlands
    6. Department of Medical Microbiology,
    7. Academic Medical Centre,
    8. Meibergdreef 9,
    9. 1105 AZ Amsterdam,
    10. The Netherlands
      1. A VAN DER ENDE,
      2. P ROORDA,
      3. J DANKERT
      1. Department of Gastroenterology,
      2. Academic Medical Centre,
      3. Meibergdreef 9,
      4. 1105 AZ Amsterdam,
      5. The Netherlands
      6. Department of Medical Microbiology,
      7. Academic Medical Centre,
      8. Meibergdreef 9,
      9. 1105 AZ Amsterdam,
      10. The Netherlands

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        Editor,—van der Hulst and colleagues (Gut 1998;42:166–9) suggest that apparent metronidazole resistance predicts response to anti-helicobacter therapy regimens containing this antibiotic. However, the cure rate with their regimen of omeprazole, bismuth, tetracycline, and metronidazole for one week was only 90% (74/82). This is different from previous reports of this regimen given for seven or 12 days when 97 to 98% eradication rates were reported, and clearly antibiotic resistance was not a factor.1-3

        Perhaps the answer lies in the technique used to estimate metronidazole resistance. It seems likely that unless an anaerobic phase is incorporated into the incubation, potentially misleading results may be obtained.4 5

        Locally an apparent 19% metronidazole resistance rate found in an entirely micro-aerophilic culture fell to only 2% when an anaerobic phase was incorporated in the incubation in line with the suggestion of the manufacturer of the E-test system.5 This correlates well with our 97% eradication rate in Helicobacter pyloriurease positive patients with spontaneous duodenal ulcer treated with a regimen of lansoprazole, tetracycline, clarithromycin, and metronidazole, the antibiotics being given for one week.6

        Encouraging results can be obtained with vigorous regimens if the right drug combination is selected, but laboratory studies may not be as helpful as they first appear.

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        Reply

        Editor,—We thank Dr Bateson for his comments on our paper. Dr Bateson doubts that the lower eradication rate (compared with his studies and those by others from the Netherlands) observed in our patient population correlates with a higher prevalence of metronidazole resistant Helicobacter pylori because of the possible use of inappropriate methodology to assess metronidazole sensitivity.

        However, in our study H pylori eradication rates of 98% were achieved in patients infected with metronidazole susceptible strains. These results are similar (even superior) to those from the cited Dutch studies which were conducted in areas with a low prevalence of metronidazole resistance (at that time around 3%, assessed by the same method as in our study). By contrast, in those patients who were infected with metronidazole resistant strains, eradication efficacy was significantly lower at 82%. In addition, Dr Bateson used a different quadruple regimen to that used in the Dutch studies, using clarithromycin instead of bismuth. The clarithromycin containing quadruple regimen might be more effective than the bismuth one, making comparison of efficacy difficult, if not impossible.

        Dr Bateson comments that incorporation of an anaerobic phase into the incubation may lead to a drop in the frequency of metronidazole resistance. However, we do not know the clinical relevance of this in vitro phenomenon.

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