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Treatment of Helicobacter Pylori Infection.

Last updated on September 9, 2021

Treatment regimens

FDA approved regimens

There are three dual drug regimens in the United States, and all have similar eradication rates:

omeprazolOmeprazole (Prilosec) and clarithromycin (Biaxin).

The eradication rate with this regimen was 78 percent in U.S. trials and 82 percent in European trials. Compliance has generally been good, and the regimen is generally well tolerated. The principal side-effect is taste perversion due to clarithromycin.

Ranitidine bismuth citrate (Zantac) and clarithromycin (Biaxin).

Ranitidine bismuth citrate is a new compound that is a highly soluble form of bismuth. An eradication rate of 82 percent was reported in the United States. Higher eradication rates have been reported in European studies.

There is only one study that compares two dual therapies in a randomized trial. In this study, eradication rates were lower than in other reports and were significantly better for the combination of ranitidine bismuth citrate with clarithromycin (73 percent) compared to omeprazole with clarithromycin (53 percent).

Bismuth-based triple therapy.

Bismuth-based triple therapy consists of a combination of bismuth, metronidazole and tetracycline. Amoxicillin has been used instead of tetracycline with poorer results. The three drugs are generally co-prescribed with an anti-secretory drug (H2 receptor antagonist or proton pump inhibitor) in patients with peptic ulcer disease.

With this regimen, 16-18 pills need to be taken every day, which affects compliance. Eradication rates as high as 95 percent have been reported in some studies, but the overall eradication rate is probably lower in U.S. studies and averages 82 percent.

Other regimens: short triple therapies

To decrease cost and enhance compliance, shorter periods of therapy have been tried with a variety of agents, administered twice a day. These regimens are generally simpler to take, and lower doses of some drugs reduce side-effects.

Proton pump inhibitor based triple therapies.

Proton pump inhibitors (lansoprazole [Prevacid], omeprazole [Prilosec]) used in combination with two antibiotics are a major advance in the therapy of H. pylori infection. Two large European trials have shown a high degree of efficacy. Seven, 10 and 14-day therapy have been reported to yield similar results in European studies, but in the United States, a decrease in efficacy has been reported with seven-day therapy, and at the current time, 10-day therapy is preferred by some experts.

As all drugs are given twice a day, compliance is enhanced. The best results are with combinations of a proton pump inhibitor, amoxicillin and clarithromycin or the combination of a proton pump inhibitor with metronidazole and clarithromycin.

Treatment of Helicobacter Pylori Infection.Ranitidine bismuth citrate triple therapy.

Data from Europe and the United States have shown high eradication rates with ranitidine bismuth citrate in combination with amoxicillin and clarithromycin or metronidazole and clarithromycin.

High eradication rates have also been reported with a combination of ranitidine bismuth citrate and metronidazole and clarithromycin in Europe. In the United States, an eradication rate of 95 percent was reported for the combination of ranitidine bismuth citrate with amoxicillin and clarithromycin and 87 percent for ranitidine bismuth citrate with metronidazole and tetracycline.

Problems with therapy in the community

While controlled trials provide a measure of efficacy with a given regimen, the results do not necessarily translate into routine clinical practice. The principal problems in routine practice are compliance and resistance.


Compliance with therapy is an important variable that affects results with all of the treatment regimens. Compliance is a particular problem with bismuth-based triple therapy because of the number and frequency of the pills that need to be taken and the relatively high incidence of minor side-effects.

Decreased compliance is associated with a decrease in eradication rates. A blister pack of each day’s medication has been developed for bismuth-based triple therapy, but it is considerably more expensive than the cost of the drugs bought individually.


Primary resistance to metronidazole is an important problem in some populations. Resistance rates from 24 to 70 percent have been reported in the United States, and eradication rates with metronidazole-containing regimens are decreased when resistance is present.

A recent study found much higher prevalence rates of metronidazole resistance (47 to 66 percent) throughout the United States. Clarithromycin resistance rates have been increasing with time in the United States, from three to four percent in 1994 to approximately 13 percent in 1996. Clarithromycin resistance is associated with a decreased efficacy with clarithromycin containing regimens.

Effectiveness of therapy in routine clinical practice

In a community-based study of gastroenterologists, Fennerty et al. showed that the combination of metronidazole, omeprazole and clarithromycin had an eradication rate of 92 percent, while omeprazole and clarithromycin dual drug therapy had an eradication rate of 76 percent, and bismuth based triple therapy had an eradication rate of 73 percent. Data on eradication rates in the community with primary care providers providing therapy are still lacking. A recent study suggests that only 39 percent of patients with peptic ulcer disease were tested for Helicobacter pylori, and of these, only half received treatment with antimicrobials.

Cost-effectiveness models of different regimens

Computer models that estimate the cost of therapy with several of the regimens have been developed. Vakil et al. compared four treatment regimens for the eradication of H. pylori and demonstrated that a strategy to eradicate H. pylori was considerably less expensive than traditional H2 receptor antagonist therapy even if the cost of the H2 receptor antagonist was decreased to $1 for the entire year of maintenance of therapy. This is because the principal determinant of cost with Helicobacter pylori eradication therapy is the cost of recurrence.

Regimens with high eradication rates are cost-effective regardless of the initial cost of the drug therapy. This model is relevant to the managed care environment because costs were assessed over a two-year time frame. In another model based on actual eradication results in a community-based trial (effectiveness data), we found that the expected costs with proton pump inhibitor based triple therapy were lower than with two drug therapies. The new short triple drug therapies should replace dual drug therapies as the treatment of choice for H. pylori infection.

In summary, despite significant advances in our understanding of the pathogenesis and treatment of Helicobacter pylori related infection, treatment of patients in the community is incomplete and inadequate.

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