Background: A third line treatment is needed in roughly 5% of patients infected with Helicobacter pylori. Few data have been reported on efficacy of treatment regimens in these patients. Methods: A prospective trial was designed to study the effectiveness of third line treatment of H. pylori infection in ulcer patients. Two‐week quadruple, culture‐guided, combinations were used in 31 consecutive patients. Susceptibility to metronidazole and clarithromycin were studied by E‐test, and thereafter a predetermined treatment regimen was used. Compliance was evaluated by pill count, and eradication defined by negative urea breath test at 6 weeks. Results: Two main quadruple regimens were used in 29 patients. In spite of good compliance, the combination of omeprazole, tetracycline, bismuth and clarithromycin (OTBC) showed an eradication rate (per protocol analysis) of 36% (five out of 14; CI: 12.8–64.9), and if amoxycillin was used (OTBA) the rate was 67% (eight out of 12; CI: 34.9–90.1). The difference was not significant. No clinical factor was found to be associated with failure to eradicate. Conclusions: Third line treatment often fails to eradicate H. pylori infection. New strategies need to be developed and tested for this common clinical situation.

Background : Clarithromycin is a key antimicrobial in the combinations used to cure Helicobacter pylori infections, so there is a need to define the impact of in vitro resistance on in vivo results. Methods : A prospective trial was designed to study the effectiveness of the 1‐week combination of lansoprazole, clarithromycin and amoxycillin in 102 consecutive patients with active peptic ulcer. The pre‐treatment and post‐treatment sensitivity to amoxycillin, metronidazole and clarithromycin were studied by E‐test, and H. pylori status was defined by histology, culture and urease test at diagnosis and one month after treatment, and by urea‐breath test 2 months after treatment. Results : The eradication rate (intention‐to‐treat analysis) was 77% (95% CI: 69–86). No clinical factor was found to be different between eradicated and non‐eradicated patients. Clarithromycin‐resistant strains were found in 10 (10%; CI: 5–17) patients. The eradication rate was 20% (CI: 3–56) in these patients vs. 83% (CI: 75–91) in patients harbouring clarithromycin‐sensitive strains (P < 0.001). A logistic‐regression analysis confirmed clarithromycin resistance as the only factor associated with treatment failure. Conclusions : Clarithromycin resistance significatively impairs the effectiveness of the combination of lansoprazole, amoxycillin, and clarithromycin. The 80% efficacy goal will be difficult to reach in areas with high (>10%) primary clarithromyicin resistance, if currently recommended proton pump inhibitor‐triple therapies are used.

Quadruple therapy obtains a high eradication rate even in patients with clarithromycin- and metronidazole-resistant strains. Further randomized and controlled studies are warranted and are urgently needed.

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