Treatment of Helicobacter pylori Infection

Treatment regimens for Helicobacter pylori infection have undergone rapid evolution in a short time. In 1998, Breuer et al., 1 from Houston, TX, U.S.A., published their findings from a survey of U.S. gastroenterologists and primary care physicians that they had conducted during 1996. They documented 103 different regimens in use. Since then, the American College of Gastroenterology (ACG) has published its recommendations about the management of H. pylori infection. 2 Among the treatment regimens specifically endorsed in the ACG guidelines were triple combinations of a proton pump inhibitor (PPI) along with clarithromycin and either amoxicillin or metronidazole. However, even these recently published guidelines now appear slightly dated. For instance, some now consider that triple regimens comprising a PPI, clarithromycin, and metronidazole should no longer be advised. 3 There are fears that resistance may develop to both clarithromycin and metronidazole in patients whose infection is not cured by a course of such treatment. Because eradication rates with PPI-based triple regimens may only be 80–83% by intent-to-treat analysis, 4 as many as one in five patients treated with a PPI, clarithromycin, and metronidazole may be at risk of developing strains of H. pylori that are resistant to both of the antimicrobials. This makes re-treatment especially difficult. However, a recent report found no amoxicillin-resistant strains of H. pylori among 316 isolates from patients in the United States. 5 For that reason, the combination of a PPI, clarithromycin, and amoxicillin should be considered first-line treatment for patients with H. pylori infection, unless they are allergic to penicillin. The Food and Drug Administration has approved triple regimen comprising either lansoprazole or omeprazole along with clarithromycin and amoxicillin. The combination of lansoprazole, clarithromycin, and amoxicillin was initially approved as a 14-day treatment. However, it was subsequently shown that similar eradication rates could be achieved using the same regimen for only 10 days. 6 The combination of omeprazole, clarithromycin, and amoxicillin is approved as a 10-day treatment. Recent surveys of gastroenterologists 7 and Internal Medicine residents 8 have found that PPI-based triple regimens given for 10 or 14 days are the most frequently prescribed for H. pylori infection. Elsewhere, including Canada 9 and Europe, 10 PPI-based triple regimens are generally prescribed for 7 days. In multinational studies including European countries and Canada, PPI-based triple regimens given for only 7 days have produced consistently high eradication rates. 11–13 In the United States, however, 7 days of treatment appears to be inadequate. 14 The explanation for this apparent difference between the United States and other countries has not been satisfactorily explained. This edition of the J Clin Gastroenterol contains a report of a study from Italy that compares two eradication regimens given for even shorter periods. 15 Dr. Catalano et al. 15 treated their patients with clarithromycin and amoxicillin in standard U.S. dosages for 5 days having pre-treated with either omeprazole or pantoprazole for 2 days. By per protocol analysis, the infection was eradicated 1 month later in 95% of the omeprazole group and 84% of the pantoprazole group—a statistically nonsignificant difference. Healing of duodenal ulcer was documented in 95% of the omeprazole group and 88% of the pantoprazole group 1 month after treatment. Thus, roughly 1 omeprazole-treated patient in 20 and 1 pantoprazole-treated patient in 12 did not have initial healing of their ulcer. After 1 year, there was 100% ulcer healing in both groups among the evaluable patients. Thus, although all ulcers eventually healed, this short treatment left some patients with persistent ulceration for longer than desirable. The investigators gave either PPI as a single morning dose rather than twice daily, which is what is generally recommended. They also pretreated their patients with either PPI for 2 days before the initiation of antibiotic treatment. This was presumably to elevate intragastric pH at the time of antibiotic intake to maximize the local antimicrobial action. In doing so, they saved their patients 2 days of antibiotic treatment and still produced eradication rates comparable to those seen elsewhere in Europe using 7-day regimens with all agents started simultaneously. However, they may also have complicated the regimen unnecessarily. When giving a relatively complex regimen of three drugs, it is probably wise to simplify it as much as possible for patients. The Italian group has shown that the two PPIs they investigated were of equivalent efficacy in these combination regimens against H. pylori and that short courses of treatment work well in Italy. However, we cannot—and should not—immediately extrapolate this to the United States.