No Added Benefit of Higher Doses of bismuth or antibiotics in H. pylori Quadruple Therapy: Study

This paper's background is associated with the "Hp-EuReg" project, which is an international, prospective, and non-interventional registry, following the therapy of Helicobacter pylori infection in Europe by gastroenterologists. Quadruple therapy with bismuth agents was empirically examined from 2013 to 2024 to establish whether increased dosage would improve the clinical outcome. This study found out that standard quadruple therapy is very efficient when administered appropriately; however, "more" does not mean "better," since increasing dosage did not make much difference in the rate of success among various treatment approaches.

Key findings:

• The analysis of 10,767 first-line treatment cases offered an insight into the precise limits that need to be reached for a successful outcome.
• In terms of the CAB combination, the study revealed that the efficacy was >90% with the use of standard doses of amoxicillin (2,000 mg/day) and clarithromycin (1,000 mg/day).
• There was no increase in the efficiency rate regardless of how much higher the bismuth dose became.
• Moreover, for the BMTc approach, the efficiency was >90% only when tetracycline was given at geq1,500 mg/day, metronidazole was prescribed at 1,500 mg/day, and bismuth was administered at geq480 mg/day.
• In other quadruple approaches, the AMB therapy demonstrated geq90% efficiency with 2,000 mg of amoxicillin, geq1,000 mg of metronidazole, and geq480 mg of bismuth in the mITT analysis.
• Also, the CMB therapy achieved geq90% efficiency with geq800 mg of metronidazole per day.
• The efficiency rate did not increase further despite rising levels of bismuth.
• Additionally, in ALB therapy, there was evidence that 500 mg/day of levofloxacin was enough since a higher dose failed to have any clinical effect.

Increasing the dosage levels of either bismuth or antibiotics above current standardized treatment guidelines is not the key to improving Helicobacter pylori eradication. It is noted that the limit to the efficacy of these medicines has already been pinpointed, and exceeding that limit will only result in higher chances of adverse reactions without an improvement in success rates. In future research, it would be more appropriate to concentrate on maximizing treatment periods, assuring maximum adherence from patients, and choosing the most potent acid suppression medications for the optimum working condition of antibiotics.

Reference:

Martínez-Domínguez, S. J., Lanas, Á., Ceamanos, E., Voynovan, I., Jonaitis, L., Vologzanina, L., Lucendo, A. J., Fadieienko, G., Sarsenbaeva, A. S., Starostin, B. D., Zaytsev, O., Mahmudov, U., Abdulkhakov, S. R., Sagdati, S., Tatiana, I., Bakulin, I., Pabón-Carrasco, M., Gridnyev, O., Garre, A., … Hp-EuReg investigators. (2026). Higher doses of Bismuth and antibiotics do not improve H. pylori treatment effectiveness: results from the Hp-EuReg. Clinical Gastroenterology and Hepatology: The Official Clinical Practice Journal of the American Gastroenterological Association. https://doi.org/10.1016/j.cgh.2026.03.029