How to Effectively Use Bismuth Quadruple Therapy

Bismuth triple therapy was the first effective Helicobacter pylori eradication therapy. The addition of a proton pump inhibitor helped overcome metronidazole resistance. Its primary indication is penicillin allergy or when clarithromycin and metronidazole resistance are both common. Resistance to the primary first-line therapy have centered on complexity and difficulties with compliance. Understanding regional differences in effectiveness remains unexplained because of the lack of studies including susceptibility testing and adherence data. We discuss regimen variations including substitutions of doxycycline, amoxicillin, and twice a day therapy and provide suggestions regarding what is needed to rationally and effectively use bismuth quadruple therapy.

Key points

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Bismuth quadruple therapy, consisting of a proton pump inhibitor, bismuth, metronidazole, and tetracycline, is a good alternative first-line therapy and is especially useful when penicillin cannot be used or when clarithromycin and metronidazole resistance is common.
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The literature is confusing because bismuth quadruple therapy is used to denote regimens that differ greatly in terms of duration, doses, and administration in relation to meals.
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Proton pump inhibitors can help negate the deleterious effects of metronidazole resistance in bismuth quadruple therapy. The optimum dose of proton pump inhibitor is unclear. A double dose twice a day is recommended.
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In the presence of metronidazole resistance, the optimum duration is 14 days along with 1500 to 1600 mg of metronidazole in divided dosages. The optimum doses and dosing intervals for tetracycline and bismuth are as yet unclear.
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Poor patient adherence is a major issue with bismuth quadruple therapy. Patient education and counseling regarding the goals of therapy, the side effects, and the necessity to complete the full 14 days should be provided.
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As with all therapies, the decision to use bismuth quadruple therapy should be guided by the regional, local, and patient-specific antimicrobial resistance patterns and knowledge about effectiveness locally.
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Twice-a-day dosing may provide a high cure rate with fewer side effects, accomplishes a reduction in total antibiotic dose, and improves adherence. However, its effectiveness in relation to metronidazole resistance remains unclear.