Treatment

Antibiotic regimens that eradicate H. pylori can cure peptic ulcers and are now the standard agents used for ulcers in infected individuals who are not taking NSAIDs. (Eliminating H. pylori can also cure the rare MALT lymphomas caused by this bacterium.) Other agents, such as proton-pump inhibitors or H2 blockers, are useful for relieving ulcer symptoms.

Test and Treat: Candidates for Antibiotic Therapy and Elimination of H. Pylori

Patients with Clear Evidence of Ulcers. Antibiotics are clearly indicated for patients who have both ulcers and H. pylori infection. In spite of such clear indications, however, European and American studies continue to suggest that many doctors are still only treating symptoms and not curing the ulcers themselves. (Studies also suggest that most doctors are not counseling patients properly on the potential dangers of NSAIDs and other drugs that can cause ulcers.)

There is considerable debate about whether to test for H. pylori and then treat infected patients who have dyspepsia but who have no signs of ulcers.

Managing Patients with Dyspepsia and No Evidence of Ulcers

The best approach for treating dyspepsia is highly controversial. The options include the following:

• Test and Treat. This approach involves testing for H. pylori and eradicating the bacteria in infected patients.
• Prescribing potent acid-suppressing agents. This approach generally employs a trial of potent acid-suppression drugs called proton-pump inhibitors, such as omeprazole (Prilosec) or esomeprazole (Nexium).

In either case, endoscopy is usually performed if symptoms persist after four weeks. (Some evidence suggests that PPIs may mask ulcers, so patients taking these drugs may need to discontinue them for two weeks before endoscopy.)

Arguments for Testing and Treating Patients with Dyspepsia. The argument supporting testing and treating patients with non-ulcer dyspepsia are as follows:

• Protection against ulcers. Some evidence suggests that antibiotic treatments for infected patients with dyspepsia may prevent ulcers from developing. A study in 2002, for example, found that antibiotic regimens to eradicate H. pylori greatly decreased the likelihood of ulcers in infected patients with nonulcer dyspepsia who were also on long-term NSAIDs.
• Protection against gastric cancer. Some evidence suggests that eradicating H. pylori may prevent or delay the onset of stomach cancer in people with long-term dyspepsia who are infected with the bacteria. For example, a large 2001 study in Japan, where gastric cancer is especially common, found that such cancers developed in about 3% of infected patients with nonulcer dyspepsia. However, none occurred in dyspeptic patients who were treated with antibiotics for H. pylori.

Arguments Against Testing and Treating Patients with Dyspepsia. The arguments against testing and treating are as follows:

• Lack of significant effect on symptoms. Studies are mixed on whether antibiotics have much effect on dyspepsia symptoms. For example, in a 2003 study, overall symptom scores after a year where not significantly different between dyspeptic patients who were treated for H. pylori and patients who were maintained on PPIs.
• Lower rates of H. pylori in the US. The numbers of people with H. pylori infection is declining in the US, possibly making the test-and-treat approach too expensive considering the number of people it helps.
• Increased risk for gastroesophageal reflux disease (GERD). A number of studies suggest that H. pylori in the intestinal tract protects against gastroesophageal reflux disease (GERD), which in severe cases, can be a risk factor for cancer in the esophagus. Eliminating H. pylori may also have other adverse effects.
• Overuse of antibiotics. Concern that such treatments without clear evidence of ulcers will lead to unnecessary antibiotic prescriptions, increasing the risk for side effects. Overuse may also contribute to a growing public health problem--the emergence of bacteria that are resistant to antibiotics.

Antibiotic and Combination Drug Regimens for Patients with Clear Evidence of Ulcers

The standard treatment regimen for H. pylori uses two or three antibiotics and a PPI. Cure rates after antibiotic treatment range from 70% - 90%. A typical regimen contains three drugs:

• A PPI. These drugs include omeprazole (Prilosec), lansoprazole (Prevacid), esomeprazole (Nexium), and rabeprazole (Aciphex). Proton-pump inhibitors are important for all types of peptic ulcers and a critical partner of antibiotic regimens. They reduce the acidity in the intestinal tract, and increase the ability of antibiotics to destroy H. pylori.
• Two antibiotics. Standard antibiotics are clarithromycin (Biaxin) and amoxicillin. (Some doctors substitute the antibiotic metronidazole (Flagyl) for clarithromycin or amoxicillin.)

This combination treatment is typically taken for at least 14 days. Many studies, however, suggest that a 7-day treatment may work just as well. A report published in 2006 evaluated a shorter course of treatment using rabeprazole (Aciphex), a PPI, and two antibiotics. They found that a 4-day treatment eradicated H. pylori and was associated with fewer side effects.

Follow-Up. Follow-up testing for the bacteria should be done no sooner than 4 weeks after therapy is completed. Test results before that time may not be accurate.

In most cases, drug treatment relieves symptoms of ulcers. However, symptom relief after treatment does not always indicate success, nor does persistence of dyspepsia necessarily mean that treatment has failed. Heartburn and other symptoms from gastroesophageal reflux disease (GERD), for example, sometimes worsen and require acid-suppression agents.

Failure. Treatment fails in about 15% of cases. Most often this is because patients fail to adhere to the regimen. Compliance with standard antibiotic regimens have been poor for the following reasons:

• The triple-drug regimens are complicated and require many pills. Helicide or two-drug combinations may help offset this problem.
• Side effects from the H. pylori regimens occur in up to 30% of patients. Gastrointestinal problems are very common, and cases of severe diarrhea have occurred during treatment.

Treatment may also fail if the patients harbor strains of H. pylori that are resistant to the antibiotics used. This is an increasing problem with some of the antibiotics used in the regimens. In such cases, different drugs will be tried.

Reinfection After Successful Treatment. Studies are indicating that, at least in developed countries, once the bacteria are eliminated, recurrence rates are low, well below 1% per year. Reinfection with the bacteria is possible, however, particularly in areas where the incidence of H. pylori is very high and sanitary conditions are poor. In such regions reinfection rates are between 6% and 15%.

Potential Adverse Effects from the Elimination of H. pylori

Weight Gain. Weight gain may be a problem in some cases.

Gastroesophageal Reflux Disease. Of ongoing interest are reports of a lower incidence of H. pylori in patients with GERD. (GERD is inflammation in the esophagus, or food pipe, and the most common cause of heartburn.) There are some important unanswered questions associated with this issue:

• Is the lower incidence of H. pylori in GERD patients significant, and does the bacterium actually protect against GERD? Studies are still not conclusive in showing any significant risk for GERD in people who are not infected with H. pylori, except possibly in certain regions. In a 2003 study, for example, the absence of H. pylori infection in people with GERD was more pronounced in Asian patients compared to those in Europe and North American.
• Does eliminating the bacteria with antibiotic therapy actually produce GERD in some people? One study, for instance, observed that patients with cured infections of H. pylori were twice as likely to develop GERD as those who remained infected. However, a 2003 analysis of eight studies reported no higher risk for GERD after antibiotic treatments. In addition, GERD patients did not experience worsening of symptoms. Longer follow-up studies are needed however to determine long-term consequences, if any.
• How should people who have GERD and are infected with H. pylori be managed? Patients with severe GERD usually require on-going proton-pump inhibitors (PPIs), such as omeprazole (Prilosec), which are powerful acid-suppressors. Some evidence suggests that in such patients, the combination of H. pylori and chronic acid suppression may lead to atrophic gastritis--a precancerous condition in the stomach. Current guidelines then advocate eliminating the bacteria with antibiotics. There is some concern that once the bacteria is eliminated, however, GERD may worsen, which can pose a risk for Barrett's esophagus--also a precancerous condition. (On the encouraging side, however, evidence to date does not suggest any higher risk for more serious GERD complications after H. pylori is eliminated.)

Effects on Other Gastrointestinal Infections. Some evidence exists that H. pylori protects against E. coli and other GI infections in children, particularly those that cause diarrhea. If true, then treating infected children for H. pylori should be undertaken very cautiously and only with evidence that the bacteria is causing harm.

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