Sequential Therapy for H. pylori Eradication

In this study, sequential therapy was more efficacious than simultaneous therapy, but the mechanism underlying its success remains unexplained.
Standard triple therapy for Helicobacter pylori infection consists of a proton-pump inhibitor and two antibiotics, administered simultaneously. Increasing resistance to two commonly used antibiotics, metronidazole and clarithromycin, has decreased the efficacy of this approach to less than 80% in North America and Europe. Small studies have suggested that sequential, rather than simultaneous, antibiotic therapy might improve eradication rates. Researchers explored this possibility in a double-blind study that involved 300 adults in Italy with dyspepsia or peptic ulcers.
Participants were evaluated by endoscopy (with biopsies for histologic evaluation, culture, and urease testing) and by urea breath testing to confirm H. pylori infection. They then were randomized to receive standard therapy twice daily for 10 days (pantoprazole [40 mg], amoxicillin [1 g], and clarithromycin [500 mg]) or sequential therapy (pantoprazole [40 mg], amoxicillin [1 g], and placebo twice daily for 5 days, followed by pantoprazole [40 mg], clarithromycin [500 mg], and tinidazole [500 mg] twice daily for 5 days). Follow-up breath testing was performed at 4 and 8 weeks after completion of therapy. Eradication was defined as negative results on both tests.
Per-protocol analysis revealed eradication rates of 93% for sequential therapy and 79% for standard therapy (P=0.001). Among patients with clarithromycin-resistant H. pylori strains, eradication rates were higher with sequential than with standard therapy (89% vs. 29%; P=0.003), but, among those with metronidazole-resistant strains, rates were similar in the two treatment arms (97% vs. 91%). Among patients with strains that were resistant to both clarithromycin and metronidazole, none of four sequential-therapy recipients, versus two of seven standard-therapy recipients, achieved eradication. Side effects were mild and similar between groups. The authors concluded that sequential therapy might be more effective than standard triple therapy and should be considered as a possible first-line therapy for patients with H. pylori infection.
Comment: These results provide important information about how to address the dropping success rates for H. pylori eradication therapy in North America and Europe. The mechanism underlying sequential therapy’s superiority in this trial remains unclear. Initial therapy with amoxicillin might increase the efficacy of clarithromycin in the second phase of treatment; however, the results also could be due to the addition of a new drug, tinidazole, to the standard regimen. Additional studies should be performed to clarify the mechanism and generalizability of this effect.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
Published in Journal Watch Gastroenterology June 15, 2007
Citation(s):
Vaira D et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: A randomized trial. Ann Intern Med 2007 Apr 17; 146:556-63.