Sequential vs. triple therapy for Helicobacter pylori infection: a new treatment regimen guided by place and time

Image: T.Tsutsumi

Key study points:

1. Sequential treatment is more efficacious than triple therapy as the first-line treatment for H. pylori.

2. Local prevalence of H. pylori antimicrobial resistance should guide selection of treatment regimen.

Primer: In 2005, the Nobel Prize in Physiology or Medicine was awarded to Marshall and Warren for their discovery that Helicobacter pylori was the causative agent behind most cases of peptic ulcer disease and gastritis. H pylori is an organism uniquely adapted to the milieu of the human stomach. Its production of urease, an enzyme that secretes ammonia, allows it to neutralize gastric acid and survive in the harsh environment of the stomach. Further, its robust motility enables it to invade the gastric mucosa, bind on to epithelial cells, and secrete exotoxins that stimulate host cell cytokine production. The resulting chronic infection is also thought to destroy somatostatin-secreting cells in the pyloric antrum, resulting in increased gastric acid secretion and thus formation of peptic ulcers and duodenal ulcers.

Moreover, studies of this elusive, spiral shaped, gram-negative bacterium have revealed that it is not only a risk factor for gastrointestinal ulcers but it may also underlie the development of gastric cancer and MALT lymphoma. Even more worrisome, H. pylori has proven to be an incredibly common pathogen, colonizing the gastric mucosa of 50% of the global population, with higher rates found in developing countries compared to industrialized nations.

Triple therapy has remained the standard of care for H. pylori infection for nearly two decades. However, data suggests that the efficacy of this treatment regimen has dropped to <80%. Indeed, antimicrobial resistance to the mainstay treatments is increasing. Therefore the authors of this study sought to investigate the efficacy of triple therapy versus sequential drug therapy and the relationship of treatment outcomes to antimicrobial resistance.

Background reading:

1. Helicobacter pylori Infection

2. Efficacy of 5-Day Levofloxacin-Containing Concomitant Therapy in Eradication of Helicobacter pylori Infection

3. Which Therapy for Helicobacter pylori Infection?

4. Treatment regimens for Helicobacter pylori

This [randomized] study: In this randomized, open-label, multicenter study, 900 Taiwanese patients age 20 years or older with documented H pylori infection were randomly allocated into three treatment groups: sequential treatment for 10 or 14 days (designated S-10 or S-14, respectively) or triple therapy for 14 days (designated T-14). Sequential treatment consisted of lansoprazole + amoxicillin for the first 5-or-7 days, followed by lansoprazole + clarithromycin + metronidazole for remaining 5-or-7 days (for S-10 or S-14, respectively). Triple therapy consisted of lansoprazole + amoxicillin + clarithromycin for 14 days.

H pylori eradication rates were 90.7% (95% CI 87.4–94.0) for S-14, 87.0% (95% CI 83.2–90.8) for S-10, and 82.3% (95% CI 78.0–86.6) for T-14. Further, drug susceptibility testing revealed that S-14 was the most efficacious treatment in most regions studied except where there was low (<5%) clarithromycin resistance and high (>80%) metronidazole resistance.

In sum: The investigators of this study found that 14 days of sequential therapy was superior to 14 days of triple therapy, with 90.7% H. pylori eradication rates in patients receiving the sequential 14 day treatment compared to only 82.3% in patients given triple therapy. Susceptibility testing further supported these findings, suggesting that T-14 was a poor choice for treatment in most regions studied compared to S-14.

While this study’s findings may lay the groundwork for new H. pylori infection treatment regimens, it faces several major limitations. First, the subjects of the study represented only one country (Taiwan). Given the shared geography and similar genetics of this island’s inhabitants, the findings presented in this article may not be generalizable to a more diverse world population. Second, while these findings are significant, sequential therapy may prove difficult to implement clinically, particularly in low resource settings where cost and antibiotic availability may be a challenge. Third, complex treatment regimens may erect a communication barrier between physicians and patients thereby decreasing adherence. Fourth, the prevalence of antimicrobial resistance is not well established in many resource poor locations. Finally, future studies are needed to confirm the generalizability of this study’s findings and to compare the efficacy of sequential therapy with quadruple therapy.

Click to read the study in The Lancet

Click to read the accompanying editorial in The Lancet

By [ME] and [MK]

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