Understanding treatment guidelines with bismuth and non-bismuth quadruple Helicobacter pylori eradication therapies

Abstract

Recent Helicobacter pylori treatment guidelines recommend the 4-drug combinations bismuth quadruple therapy and concomitant therapy. Areas covered: We review antimicrobial therapy for H. pylori in the context of antimicrobial therapy in general and specifically in relation to good antimicrobial stewardship (defined as optimal selection, dose, and duration of an antimicrobial that results in the best clinical outcome for the treatment of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance). Expert commentary: The lack of regional and local H. pylori susceptibility data prevents implementation of susceptibility-based antimicrobial therapy and forces compromises. Bismuth quadruple therapy employing at least 1,500 mg of metronidazole for 14 days is effective despite metronidazole resistance. The main drawback is side effects causing reduced adherence. Versions where amoxicillin replaces metronidazole or tetracycline also appear effective. It is likely that bismuth quadruple therapy can be simplified by giving bismuth and possibly tetracycline b.i.d., possibly with fewer side effects. Concomitant therapy (a proton pump inhibitor, metronidazole, clarithromycin, amoxicillin) is ineffective with dual clarithromycin-metronidazole resistance and all patients receive at least one unnecessary antibiotic thus promoting antimicrobial resistance worldwide. Concomitant therapy should be abandoned when susceptibility testing becomes widespread or an alternate becomes available.

Keywords: Amoxicillin; Helicobacter pylori; antibiotic misuse; antimicrobial stewardship; bismuth; clarithromycin; metronidazole; proton pump inhibitor; resistance; susceptibility; tetracycline; vonoprazan.

Figure 1.

Algorithm showing the treatment of patient with metronidazole susceptible and resistant infections. Best results with PPI, amoxicillin, metronidazole therapy are achieve with 14 day therapy whereas only 7 day therapy is required for bismuth triple or quadruple therapy. In contrast, high dose metronidazole and 14 day duration are best for metronidazole resistant infections.

Figure 2.

Hp-treatment nomogram [28] illustrating the effective of clarithromycin resistance on the cure rate of a 14 day PPI, clarithromycin, amoxicillin triple therapy in a western population using 20 mg of omeprazole b.i.d. (solid line). The cure rate with susceptible H. pylori infections is expected to be ≥95%. The dotted line shows the additive effect of twice daily bismuth which increased the cure rate by 20%. The shaded area shows cure rate of the population falls below 90% occurs when resistance exceeds about 32%.

Figure 3.

Hp-treatment nomogram illustrating the effective of clarithromycin resistance on the cure rate of a 14 day PPI, clarithromycin, amoxicillin triple therapy in an Asian population or a western population using high dose PPI (eg, >40 mg omeprazole equivalent b.i.d.) (solid line). The cure rate with susceptible infections is expected to be ≥95%. The dotted line shows the effect of increased antisecretory activity on the cure rate of PPI-amoxicillin dual therapy and additive effect of twice daily bismuth which increased the cure rate by 20%. The shaded area shows cure rate of the population falls below 90% occurs when resistance exceeds about 44%.

Figure 4.

Hp-treatment nomogram illustrating the effective of metronidazole resistance on 7 day bismuth quadruple therapy. The cure rate with resistant infections is approximately 75%. In this scenario all patients would be expected to achieve a cure rate of ≥90% with 14 day therapy with full dose metronidazole (eg, 1,500 or 1,600 mg metronidazole/day in divided doses).