Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen



H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. We aimed to identify the optimal breakpoints of antibiotic minimal inhibitory concentration (MIC) to predict the success of rescue therapy for TR H. pylori infection.


We consecutively enrolled 430 patients with at least one course of failed H. pylori eradications to receive an H. pylori culture for antibiotic MIC test. Seventy-three (17%) had TR H. pylori infection (MIC of clarithromycin > 0.5, levofloxacin > 1, and metronidazole > 8 mg/L, respectively). Sixty-nine cases with TR H. pylori infection received rescue therapy with either ATBP (amoxicillin, tetracycline, bismuth, and PPI) or MTBP (metronidazole, tetracycline, bismuth and PPI) for 7–14 days. Fourteen patients with positive 13C-urea breath test after the first rescue therapy were retreated with a crossover second rescue therapy.


The MTBP regimen had higher eradication success than the ATBP regimen as the first rescue therapy for TR H. pylori (intent-to-treat (ITT) analysis, 70.3 vs. 46.9%, p = 0.048; per protocol (PP) analysis, 78.8% vs. 51.7%, p = 0.025). For MTBP regimen, tetracycline MIC ≤ 0.094 mg/L (p < 0.001) with a 14-day treatment duration (p = 0.037) could predict eradication success with 100% accuracy. For the ATBP regimen, amoxicillin MIC selected as ≤ 0.032 mg/L could optimally determine eradication success (72.2 vs. 33.3%, p = 0.025).


Optimizing the MIC breakpoints of amoxicillin and tetracycline resistance better predicts the outcome of bismuth quadruple therapy. Further prospective studies using the revised MIC breakpoints to select antibiotics are warranted.

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This study was supported by the National Cheng Kung University Hospital clinical bacterial database.

Author information




MT Hsieh and WL Chang conceived the study and contributed equally. Patients were enrolled from all authors. MT Hsieh and WL Chang reviewed all the medical records, analyzed the data, and interpreted the results. MT Hsieh and WL Chang prepared the initial draft of the manuscript. BS Sheu coordinated the study design and improved the subsequent drafts of the manuscript. The final draft was approved for submission.

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Correspondence to Bor-Shyang Sheu.

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Hsieh, M., Chang, W., Wu, C. et al. Optimizing the MIC breakpoints of amoxicillin and tetracycline for antibiotic selection in the rescue therapy of H. pylori with bismuth quadruple regimen. Eur J Clin Pharmacol (2020). https://doi.org/10.1007/s00228-020-02938-5

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  • Triple-drug resistance
  • Helicobacter pylori
  • Rescue therapy
  • Minimal inhibitory concentration
  • Amoxicillin
  • Tetracycline