Improving Helicobacter pylori Eradication Regimens

Helicobacter pylori colonization has known costs to humans, including increased risk for peptic ulcer disease (1), gastric adenocarcinoma (2), and gastric lymphoma (3). The finding that elimination of H. pylori changes the natural history of peptic ulcer disease (4) and gastric mucosa–associated lymphoid tissue lymphoma (5) has led to the development of successful strategies to clear the organism from persons with these disorders. Over the past 20 years, regimens that use acid-suppressing agents in conjunction with several antibiotics (in particular, clarithromycin [6]) have been highly successful for H. pylori eradication (7). However, recent reports detail decreasing efficacy of these combination therapies (8). Why is this happening, and what can be done to improve therapies to eradicate H. pylori?

Some of the decrease in treatment efficacy has been due to increasing resistance of H. pylori to clarithromycin (9). This trend, now being observed in many industrialized countries, partly reflects the growing use of second-generation macrolides, which has increased 388% in the United States from 1992 to 2000 (10) and has probably been increasing since. Even a short course of clarithromycin selects for resistance within the persistent, indigenous microbiota, including Enterococcus and Staphylococcus species, in which resistant organisms may persist for years in the intestinal tract or in the skin, respectively, without any further selective pressure (11). The persistence of resistant bacteria is an important but largely overlooked consequence of antibiotic use. The same phenomenon seems to affect H. pylori (12). To address the problem of diminished efficacy of H. pylori eradication …