Standard triple therapy may no longer be best for H. pylori eradication treatment

Standard triple treatment may be losing effectiveness in most areas of the world due to increasing resistance to clarithromycin and metronidazole.


Seven days of standard triple treatment may not be the best choice for eradication of Helicobacter pylori, according to a new study.

Researchers performed a systematic review and network meta-analysis to examine the efficacy and tolerance of treatments for eradication of H. pylori infection. Randomized, controlled trials that compared different treatments in adults and were published through Dec. 20, 2013, were included, and data on 14 different treatments were compared. The study results were published online on Aug. 19 by The BMJ.

One hundred forty-three studies were included in the analysis, and 34 of 91 possible direct comparisons were performed for the efficacy outcome. The previously recommended standard triple treatment regimen consisting of 7 days of a proton-pump inhibitor plus clarithromycin plus either amoxicillin or metronidazole, appeared to be the least effective in an intention-to-treat analysis. Two other commonly used regimens, 7 days of simultaneous treatment with a proton-pump inhibitor, levofloxacin (substituted for clarithromycin), and 1 antibiotic, and 7 days of simultaneous treatment with a proton-pump inhibitor, bismuth compounds, and 2 antibiotics, were equally effective as standard triple treatment but significantly less effective than the other regimens examined.

The treatments that performed better than these 3 regimens for H. pylori eradication were:

  • 7 days of concomitant treatment (proton-pump inhibitor plus 3 antibiotics, often amoxicillin, clarithromycin, and 5-nitroimidazole, administered together),
  • 10 or 14 days of concomitant treatment,
  • 10 or 14 days of probiotic-supplemented standard triple treatment,
  • 10 or 14 days of levofloxacin-based triple treatment (proton-pump inhibitor, levofloxacin, and 1 additional antibiotic administered together),
  • 14 days of hybrid treatment (proton-pump inhibitor and amoxicillin for 7 days, followed by a proton-pump inhibitor, amoxicillin, clarithromycin, and 5-nitroimidazole for another 7 days), and
  • 10 or 14 days of sequential treatment (5 or 7 days of a proton-pump inhibitor plus amoxicillin, followed by 5 or 7 days of a proton-pump inhibitor plus clarithromycin and 5-nitroimidazole or amoxicillin).

All 14 of the treatments were well tolerated, but 2 of them—7 days of probiotic-supplemented standard triple treatment and 7 days of levofloxacin-based triple treatment—were associated with fewer reported adverse events. In addition, longer treatments tended to have better eradication rates but higher risk for adverse events.

The researchers noted that their results were limited by the inherent limitations of the included studies and added that relatively few studies were available on hybrid and concomitant regimens for H. pylori eradication. However, they concluded that although the previously recommended regimen, 7 days of standard triple treatment, was effective against H. pylori, other treatments performed better. They called for additional larger studies of various treatment regimens that include examination of antibiotic resistance.

The author of an accompanying editorial noted that standard triple treatment is losing effectiveness in most areas of the world due to increasing resistance to clarithromycin and metronidazole and agreed that data on local patterns of antibiotic resistance will be necessary to determine the best treatment regimen in a particular region.

“Sometime in the distant future, vaccination against H. pylori might solve the problem by preventing infection from early childhood onwards,” the author wrote. “Until then we will have to keep looking for the most effective antibiotic eradication regimen with the best safety profile, but it seems unlikely that this will be a ‘one size fits all’ treatment suitable for patients all over the world.”